PubAnnotation

Id	Subject	Object	Predicate	Lexical cue
T1	830-967	Epistemic_statement	denotes	The aim of the current study was to describe the largest database ever collected in France on SSI and to analyse a 6-year temporal trend.
T2	1079-1197	Epistemic_statement	denotes	In each ward, 200 consecutive surgery procedures should be included and patients followed up to 30 days after surgery.
T3	2437-2582	Epistemic_statement	denotes	Impact of the national policy on SSI incidence remains to be further evaluated, although encouraging results were evidenced for specific surgery.
T4	2769-2825	Epistemic_statement	denotes	Data on HAI surveillance in maternity units are lacking.
T5	5418-5556	Epistemic_statement	denotes	Considering that all French hospitals account for 465,494 beds, 41,276 [95% CI: 40,896-41,656] BBFE could have occurred in France in 2004.
T6	5641-5859	Epistemic_statement	denotes	Post-exposure prophylaxis (PEP) was prescribed to 4.5% of exposed personnel (vs. 5.8% in 2003 and 6.3% in 2002); this decrease may reflect the impact of April 2003 French recommendations, which reduced PEP indications.
T7	6138-6247	Epistemic_statement	denotes	Prevention through education and use of safety devices (such as blunt suture needles) may thus be a priority.
T8	7422-7487	Epistemic_statement	denotes	Skin antiseptics can prevent the contamination of blood cultures.
T9	9254-9351	Epistemic_statement	denotes	Objectives: The inanimate hospital environment can become contaminated with nosocomial pathogens.
T10	9352-9563	Epistemic_statement	denotes	Hydrogen peroxide vapour (HPV) decontamination has proven effective for the eradication of persistent environmental contamination but the rate of recontamination following HPV decontamination is largely unknown.
T11	11317-11537	Epistemic_statement	denotes	The questionnaire was composed of two parts: first part contained parameters for determination of sociodemographic properties and the second contained questions about evaluation of the knowledge about prevention from NI.
T12	11538-11685	Epistemic_statement	denotes	Questions were prepared by using the references about the subject and by the help of the executives of the cleaning staff firm and statistics unit.
T13	12186-12441	Epistemic_statement	denotes	Knowledge level was not associated with gender, educational status and duration of working as cleaning staff (p > 0.05) but mean knowledge level of the staff working in the clinics was found higher than staff working in administrative sections (p < 0.05).
T14	12685-12875	Epistemic_statement	denotes	58.8% thought that they could prevent themselves from NI by hand washing before and after cleaning process, 80.8% stated they obeyed handwashing rules and 90.4% stated that they used gloves.
T15	12939-13085	Epistemic_statement	denotes	Conclusion: Measurement of the level of the knowledge of the hospital cleaning staff may be beneficial for determination of the existing problems.
T16	13086-13188	Epistemic_statement	denotes	Periodical well-established educational programmes should be started to improve the current situation.
T17	13301-13422	Epistemic_statement	denotes	Rapid and sensitive screening methods for direct detection of MRSA are essential to limit further spread in the hospital.
T18	15955-16091	Epistemic_statement	denotes	However, recent studies indicate that the throat may be an additional important site of colonisation (Nilsson P. J Clin Microbiol 2006).
T19	17340-17437	Epistemic_statement	denotes	Additional cost can be avoided by pooling the specimens while maintaining the higher sensitivity.
T20	17438-17537	Epistemic_statement	denotes	Therefore, optimal screening for S. aureus should include swabs from both the nares and the throat.
T21	17538-17611	Epistemic_statement	denotes	This may be even more important if screening is focused on MRSA carriage.
T22	18753-19015	Epistemic_statement	denotes	Stopping the hypochlorite disinfection was associated with a sudden increase in clinical cases of MRSA from 10 to 25% over a 6 month period (p = 0.03), with levels approaching those seen prior to the start of the infection control programme in 2001 (see figure).
T23	19016-19142	Epistemic_statement	denotes	Conclusions: Stopping hypochlorite environmental disinfection was strongly associated with an increase in clinical MRSA cases.
T24	20787-20864	Epistemic_statement	denotes	vanC1 was linked to E. gallinarum, and vanC2 to E. casseliflavus as expected.
T25	21056-21190	Epistemic_statement	denotes	Whether persistence of these antibiotic resistant strains is due to selection by antibiotics or other agents deserves further studies.
T26	21723-21888	Epistemic_statement	denotes	Data from NORM-VET could form a basis for risk assessments and be a tool for targeting interventions and further to evaluate the effectiveness of such interventions.
T27	22283-22368	Epistemic_statement	denotes	Specific clinical isolates from the routine diagnostic have been included biannually.
T28	22369-22449	Epistemic_statement	denotes	The isolates have mainly been tested using a microdilution technique (VetMICTM).
T29	22839-23095	Epistemic_statement	denotes	Conclusion: Evaluation of the first six years of the programme has recognized that the relatively low number of isolates of each species and source included complicates the conclusions possible to draw from the data, especially evaluating trends over time.
T30	23096-23361	Epistemic_statement	denotes	Even though the run costs of the programme has been limited to a minimum, it is still useful for the purpose of monitoring antimicrobial resistance within a country as Norway, where the resistance problem in the animal and food sectors still is at a very low level.
T31	23475-23652	Epistemic_statement	denotes	However, the use of this source to perform risk assessments is limited as there still is a lack of even more specific data as for instance data on usage at animal or farm level.
T32	23653-23782	Epistemic_statement	denotes	O26 Comparison of antibiotic susceptibilities of Staphylococcus aureus and S. intermedius isolates from dog owners and their dogs
T33	23783-24008	Epistemic_statement	denotes	Objectives: Antibiotic resistance in veterinary isolates has been reported to be higher than in human isolates due to frequent empirical use, and there are concerns about transfer of resistance between staphylococcal species.
T34	24009-24122	Epistemic_statement	denotes	S. intermedius is the more common colonising species in dogs, but S. aureus, including MRSA, may also be present.
T35	24123-24207	Epistemic_statement	denotes	Case reports suggest there can be cross-infection between companion animals and man.
T36	24208-24359	Epistemic_statement	denotes	Increasing concern about MRSA in the community has led to recommendations for surveillance of antibiotic resistance in isolates from companion animals.
T37	26202-26306	Epistemic_statement	denotes	Veterinary use of antibiotics may increase resistance and the risk of transmission of resistant strains.
T38	31150-31245	Epistemic_statement	denotes	Conclusions: Resistance to several first-line antibacterials is a continuing problem worldwide.
T39	33055-33150	Epistemic_statement	denotes	The best example of functions associated to a plasmid is given by the antimicrobial resistance.
T40	33732-33919	Epistemic_statement	denotes	Plasmid-mediated antimicrobial resistance arises from a complex multifactorial process supported by a panoply of mobile genetic elements that contain and transfer resistance determinants.
T41	34543-34723	Epistemic_statement	denotes	Among the most important issues of clinical microbiology, increasing prevalence of bacterial pathogens expressing resistance to multiple antimicrobial agents is of special concern.
T42	34724-34896	Epistemic_statement	denotes	The observed high frequency of multiresistance suggests mechanisms by which bacterial species can concentrate and efficiently exchange a variety of resistance determinants.
T43	34897-35048	Epistemic_statement	denotes	Lateral gene transfer, which has been proposed as a fundamental process underlying bacterial diversity, is mainly mediated through plasmids and phages.
T44	35931-36065	Epistemic_statement	denotes	By inserting within a coding sequence they may inactivate the gene, or by inserting upstream of a gene they may modify its expression.
T45	36066-36140	Epistemic_statement	denotes	ISs may also help integration of plasmids into the chromosome of bacteria.
T46	36141-36369	Epistemic_statement	denotes	Some ISs, such as ISEcp1, are capable of mobilising nearby DNA, by a mechanism similar to one-ended-transposition, while others may form a composite transposon, being capable of carrying the sequence located between the two ISs.
T47	36559-36756	Epistemic_statement	denotes	The association of integrons with transferable elements may promote rapid dissemination among clinical strains, and create further opportunities for inclusion of additional resistance determinants.
T48	36757-36967	Epistemic_statement	denotes	Recently novel genetic structures, Repeated Elements (Re), have been described being capable of mobilising resistance genes through a transposition/recombination process that still needs to be fully understood.
T49	36968-37119	Epistemic_statement	denotes	The study of novel resistance mechanisms and their underlying genetic background revealed novel mobile DNA elements responsible for their mobilisation.
T50	37120-37376	Epistemic_statement	denotes	These elements are of interest for clinical microbiology, since they are associated to the emergence of novel antibiotic resistance genes, and for fundamental research, since novel genetic mechanisms for gene mobilisation and dissemination were identified.
T51	38906-39047	Epistemic_statement	denotes	This suggests that IS91 might enhance excision and integration of cassettes that are situated within replication range of IS91-like elements.
T52	39048-39175	Epistemic_statement	denotes	If the two gene capture systems are indeed engaged in a functional crosstalk this could explain their frequent co-localisation.
T53	39389-39459	Epistemic_statement	denotes	The recombinational spread of sul genes is cryptic and may be diverse.
T54	39460-39568	Epistemic_statement	denotes	However, one of the genes, sul1, is strongly linked with both integrons and common regions of the IS91 type.
T55	39569-39805	Epistemic_statement	denotes	Sulfonamides were introduced prior to other modern antibacterial drugs suggesting that it was the key selecting factor for making the dual recombinational platform of integrons and IS91-like elements fixed in most bacterial populations.
T56	39966-40008	Epistemic_statement	denotes	17th ECCMID / 25th ICC, Oral presentations
T57	40009-40226	Epistemic_statement	denotes	Bacteria are noteworthy for their remarkable genetic plasticity responding and adapting to environmental changes that often as not involves the exchanging of DNA molecules in the same cell and between bacterial cells.
T58	40554-40678	Epistemic_statement	denotes	ISCRs were also interesting in that they are intimately associated with different resistance genes carried on each integron.
T59	40679-40952	Epistemic_statement	denotes	ISCR elements have been found in many Gram-negative bacteria and have been associated with an array of different antibiotic resistant functions including qnr, ESBLs, AmpC b-lactamases, metallo-b-lactamases, aminoglycoside and chloramphenicol resistance, dhfr and sul genes.
T60	41286-41362	Epistemic_statement	denotes	These motifs have been shown to be involved in DNA recognition and mobility.
T61	41363-41496	Epistemic_statement	denotes	ISCR elements are very unusual in that, like IS91, they can mobilise large sections of adjacent DNA via a rolling circle replication.
T62	41705-41837	Epistemic_statement	denotes	Many elements are found next to class 1 integrons which we believe to be expressed and active -possibly driven by a hybrid promoter.
T63	42580-42797	Epistemic_statement	denotes	We have previously shown that Extracellular Slime Glycoliprotein (GLP) produced by all mucoid and non mucoid strains is a potent activator of NFkb transcriptional activity and TNF-a induction in fresh human monocytes.
T64	43947-44115	Epistemic_statement	denotes	Challenging of HEK-293 cells expressing only mannose receptor with Slime GLP or viable bacteria resulted in NFkb activation by 6−10 fold and 20−30 fold correspondingly.
T65	44305-44541	Epistemic_statement	denotes	Conclusion: Our results suggest that mannose receptor acts not only as phagocytosis receptor for P. aeruginosa, but also as signaling receptor and cooperates with TLR2 for maximum NFkb activation and proinflammatoty cytokine production.
T66	44626-44714	Epistemic_statement	denotes	Challenges in pharmacokinetics and pharmacodynamics S11 PK/PD in critically ill patients
T67	44715-44857	Epistemic_statement	denotes	Antimicrobial treatment of infections in critically ill patients remains a significant challenge with persisting high mortality and morbidity.
T68	44858-44954	Epistemic_statement	denotes	Early and appropriate antibacterial therapy remains an important intervention for such patients.
T69	44955-45245	Epistemic_statement	denotes	To optimise antibacterial therapy, the clinician should possess not only knowledge of the pharmacokinetic and pharmacodynamic properties of commonly used antimicrobials, but also how these parameters may be affected by the pathophysiological changes occurring during sepsis or septic shock.
T70	45246-45292	Epistemic_statement	denotes	Pathophysiological changes can be contrasting.
T71	45293-45405	Epistemic_statement	denotes	Sepsis, and the nonantibiotic treatment, increasing renal preload may result in higher antibacterial clearances.
T72	45406-45557	Epistemic_statement	denotes	Alternatively, sepsis can induce multiple organ dysfunction, including renal and/or hepatic dysfunction, causing a decrease in antibacterial clearance.
T73	45558-45727	Epistemic_statement	denotes	Aminoglycosides, b-lactams and carbapenems are distributed in plasma and interstitial space, therefore their concentrations could be dramatically affected during sepsis.
T74	45728-45801	Epistemic_statement	denotes	These drugs can have a higher Vd during sepsis leading to a reduced Cmax.
T75	45802-45950	Epistemic_statement	denotes	Some patients with serum creatinine within the normal range can have higher than normal drug clearances, thereby producing low serum concentrations.
T76	45951-46021	Epistemic_statement	denotes	If a drug needs to have a minimum serum concentration maintained (e.g.
T77	46022-46108	Epistemic_statement	denotes	b-lactams), a high drug clearance will lead to underdosage for renally excreted drugs.
T78	46109-46279	Epistemic_statement	denotes	All b-lactams should, in such patients, be administered more frequently than suggested in non-sepsis patients; administration by continuous infusion should be considered.
T79	46280-46496	Epistemic_statement	denotes	In relation to the aminoglycosides, this means that not only are large doses required to be administered, but because of a high CLCR these antibacterials may also need dosing even more frequently than every 24 hours.
T80	46643-46766	Epistemic_statement	denotes	If this were true these antibacterials would also need to have higher daily doses than proposed in the standard literature.
T81	46909-47026	Epistemic_statement	denotes	Data suggest that effective antibacterial therapy remains the most important intervention available to the clinician.
T82	47027-47189	Epistemic_statement	denotes	In treating sepsis, a clinician must be aware of the impact of the various pathophysiological and subsequent pharmacokinetic changes that can occur during sepsis.
T83	47457-47592	Epistemic_statement	denotes	In clinical practice, however, consecutive applications are common but the effect on the bacterial density on hands is largely unknown.
T84	48973-49058	Epistemic_statement	denotes	The difference between the four treatments, however, was not significant (p = 0.089).
T85	49589-49912	Epistemic_statement	denotes	Overall, a simple 1.5 min application of a well-formulated propanolbased hand rub for surgical hand disinfection keeps the bacterial density as low as possible even in two consecutive surgical procedures of 3 h. Conclusions: HPV is more effective than standard terminal cleaning for the eradication of nosocomial pathogens.
T86	50824-50894	Epistemic_statement	denotes	A/C-R was rare (0.4%) and noted in 3 nations; highest (5.5%) in Spain.
T87	53203-53347	Epistemic_statement	denotes	Persistent resistance to NA was associated with an increase in MIC, number of mutations in the gyrA and parC genes and presence of efflux pumps.
T88	53458-53611	Epistemic_statement	denotes	The carriage of E. coli NAR was not associated with the child's age or gender, use of antibiotics, or carriage of E. coli NAR among mothers and siblings.
T89	53612-53881	Epistemic_statement	denotes	Conclusions: The lack of evidence for intra-familiar spread of E. coli NAR and the significant acquisition of E. coli NAR in 2 specific DCCs suggest that other means of transmission such as the food or waterborne routs may explain the high carriage rate of E. coli NAR.
T90	53882-54042	Epistemic_statement	denotes	Persistent carriage of E. coli NAR is of concern in view of the association with an increase in both phenotypic and genetic markers of resistance to quinolones.
T91	54043-54109	Epistemic_statement	denotes	rarely cultured enterococci had a MIC90 of 2 mg/L (range, 2 mg/L).
T92	55912-56050	Epistemic_statement	denotes	This has been accomplished by enforcing preventive contact isolation of all hospitalised patients suspected or confirmed as MRSA positive.
T93	56051-56261	Epistemic_statement	denotes	This has been facilitated by the fact that in these countries the predominant risk factor for patients for MRSA acquisition was hospitalisation abroad, making these at-risk patients relatively easy to identify.
T94	57218-57319	Epistemic_statement	denotes	This could indicate that there is a continued influx of MRSA from high prevalence areas into Denmark.
T95	57320-57546	Epistemic_statement	denotes	Strains belonging to the ST80-IV complex have been the most frequent cause of CA-MRSA in Denmark, however, an increasing diversification has recently been observed including almost all strains known as associated with CA-MRSA.
T96	57633-57727	Epistemic_statement	denotes	This has happened despite continued use of contact isolation of MRSA positive patients during.
T97	57728-57917	Epistemic_statement	denotes	Hospitalisation of MRSA carriers not identified on admission due to lack of risk factors is probably one important factor responsible for the increased number of nosocomial MRSA in Denmark.
T98	57918-58177	Epistemic_statement	denotes	An increase in the prevalence of MRSA outside hospitals including in otherwise healthy persons, is thus of great concern as this not only gives rise to CA-MRSA infections but also inevitably will increase the risk of nosocomial MRSA infec-tions and outbreaks.
T99	58178-58362	Epistemic_statement	denotes	In order to keep Denmark as a low prevalence country we believe that MRSA should be contained and eradicated not only in hospitalised patients but also when diagnosed in the community.
T100	58521-58638	Epistemic_statement	denotes	The first question to ask when considering any screening programme for the identification of CA-MRSA carriage is why?
T101	58639-58703	Epistemic_statement	denotes	The importance of epidemiological data cannot be underestimated.
T102	58704-58814	Epistemic_statement	denotes	Data on prevalence can inform empirical therapy requirements or help in the design of intervention strategies.
T103	58815-58993	Epistemic_statement	denotes	Prevalence can be established for the population in general, or, specific subgroups such as children, military personnel, indigenous or disadvantaged populations can be targeted.
T104	58994-59127	Epistemic_statement	denotes	Community intervention measures similar to the 'search and destroy' techniques used in hospitals would require large-scale screening.
T105	59128-59303	Epistemic_statement	denotes	A narrower approach concentrating on high-risk groups to enable programmes such as education on hygiene to reduce transmission would allow a more targeted screening programme.
T106	59972-60064	Epistemic_statement	denotes	The value of screening healthcare workers for carriage of CA-MRSA has yet to be established.
T107	60065-60100	Epistemic_statement	denotes	How to screen is the next question.
T108	60136-60175	Epistemic_statement	denotes	Which laboratory method should be used?
T109	60176-60348	Epistemic_statement	denotes	The ideal test would have high negative and positive predictive values, be rapid, inexpensive, applicable to the routine laboratory, and have high through put capabilities.
T110	60950-60997	Epistemic_statement	denotes	The last questions are when and whom to screen.
T111	61065-61214	Epistemic_statement	denotes	The range can be from large-scale periodic population screening for epidemiological purposes to continual hospital unit, high-risk patient screening.
T112	61215-61296	Epistemic_statement	denotes	There are no established guidelines or recommendations for screening for CA-MRSA.
T113	61297-61411	Epistemic_statement	denotes	Many questions have yet to be answered particularly, whether control of transmission in the community is possible.
T114	61412-61534	Epistemic_statement	denotes	By looking at what evidence is available we can move a step closer to control of this very significant community pathogen.
T115	61914-62181	Epistemic_statement	denotes	Given that CA-MRSA has been now been implicated in healthcare-associated infections, efforts to reduce the spread of this organism within the healthcare environment are also important and include appropriate hand-hygiene, isolation, and environmental decontamination.
T116	62182-62269	Epistemic_statement	denotes	Incision and debridement remains critical in the management of most CA-MRSA infections.
T117	62270-62494	Epistemic_statement	denotes	The use of antibiotics is indicated in many CA-MRSA infections and therapeutic options include older agents, such as clindamycin, trimethoprimsulfamethoxazole, tetracyclines, and rifampin, and newer agents such as linezolid.
T118	63624-63846	Epistemic_statement	denotes	The range of receptors involved in the innate response to pneumococci in the respiratory tract is starting to be appreciated and includes Tolllike receptors and receptors primarily involved in the phagocytosis of bacteria.
T119	63847-64043	Epistemic_statement	denotes	The interaction between soluble factors and the resident phagocytes of the lung is being clarified and the complexity of cytokine networks involved in the innate host response is being elucidated.
T120	64173-64436	Epistemic_statement	denotes	Furthermore our understanding of the regulation of the inflammatory response and of the significant role of apoptosis in the regulation of the inflammatory response has lead to important insights into how cell survival and outcome of infection are closely linked.
T121	64437-64644	Epistemic_statement	denotes	These observations are enabling a more scientific interpretation of many of the central clinical features of pneumococcal pneumonia and may encourage novel approaches to therapy to improve disease responses.
T122	65029-65166	Epistemic_statement	denotes	The carrier state is more frequent in young children and may reach over 70% in some populations such as those attending day-care centres.
T123	65475-65641	Epistemic_statement	denotes	In recent years, there has been some debate on the relative contribution of serotype and genetic background to the invasive disease potential of pneumococcal strains.
T124	65642-65695	Epistemic_statement	denotes	We will present a study that addresses this question.
T125	66080-66153	Epistemic_statement	denotes	The invasive disease potential of serotypes and clones will be discussed.
T126	66154-66342	Epistemic_statement	denotes	Pneumococci cause a spectrum of diseases in humans, from reasonably mild diseases like sinusitis and conjunctivitis to potentially lifethreatening diseases like meningitis and bacteraemia.
T127	66515-66690	Epistemic_statement	denotes	Understanding invasive disease epidemiology, both preceding vaccine implementation and after vaccine introduction, is crucial to the design and development of future vaccines.
T128	66691-66902	Epistemic_statement	denotes	Several recent studies have shown that pneumococcal serotypes differ in their invasive disease potential, and this has particular relevance for the selection of serotypes to include in future conjugate vaccines.
T129	66903-67125	Epistemic_statement	denotes	It is also essential to understand the serotype-specific changes that have occurred subsequent to conjugate vaccine implementation in the USA, as a model for what might occur post-vaccine implementation in other countries.
T130	67966-68009	Epistemic_statement	denotes	Each of these presents specific challenges.
T131	68010-68220	Epistemic_statement	denotes	The vaccine has been shown to prevent between 25% and 37% of all cause X-ray confirmed pneumonias and this implies a level of protection against pneumococcal pneumonia due to vaccine serotypes in excess of 70%.
T132	68346-68496	Epistemic_statement	denotes	The major preventable burden of disease in Africa may be among HIV infected children where the vaccine has also been shown to reduce pneumonia burden.
T133	68497-68770	Epistemic_statement	denotes	An innovative aspect of the vaccine is the fact that it may reduce the pneumococcal super infections that follow viral respiratory infections, such as influenza, and conjugate vaccination of children may thus be a useful adjunct to pandemic influenza planning preparedness.
T134	68771-68999	Epistemic_statement	denotes	The interruption of carriage of vaccine serotypes has been shown to reduce IPD in adults in the USA due to herd immunity so the population benefit in an influenza pandemic may extend beyond protection just of immunised children.
T135	69000-69090	Epistemic_statement	denotes	Herd immunity has also recently been shown to protect young un-immunised infants from IPD.
T136	69091-69549	Epistemic_statement	denotes	Conjugate vaccine has had little impact on all cause otitis media in randomised trials, but post-marketing studies in the USA suggest that healthcare utilisation for otitis episodes has reduced significantly post vaccine introduction suggesting a major role for herd immunity and allowing physicians to feel more comfortable in a "wait and see" attitude to otitis once the prospects of significant complications due to the pneumococcus are likely to be rare.
T137	70143-70369	Epistemic_statement	denotes	The implementation of immunisation programmes including conjugate pneumococcal vaccine to infants in European countries affords the opportunity to monitor the impact on all of these health outcomes in both children and adults.
T138	71686-71803	Epistemic_statement	denotes	As the epidemiology of staphylococcal infections changes new therapeutic agents are becoming available to clinicians.
T139	73272-73366	Epistemic_statement	denotes	The recommended dosing regimen is an initial dose of 100 mg, followed by 50 mg every 12 hours.
T140	74239-74374	Epistemic_statement	denotes	They usually occur within the first two days of therapy, are more common in women (48%) than in men (24%), and may also be age related.
T141	74446-74622	Epistemic_statement	denotes	It has a broad spectrum of activity and its ability to evade numerous mechanisms of resistance makes it a promising solution to the treatment of multi-drug resistant organisms.
T142	74677-74841	Epistemic_statement	denotes	The increasing resistance of Gram-negative bacteria and particularly amongst Pseudomonas aeruginosa and Acinetobacter baumannii, raises a major therapeutic problem.
T143	75320-75514	Epistemic_statement	denotes	Because this drug was developed during the 1950s, only little pharmacokinetic and pharmacodynamic information are available and the optimal daily dose for severely ill patients is still unknown.
T144	75813-76034	Epistemic_statement	denotes	Clinical reports on the efficacy of intravenous colistin in these patients are not randomised studies and in most of them, colistin was frequently associated with other antimicrobial agents with a lack of a control group.
T145	76364-76486	Epistemic_statement	denotes	However recent studies demonstrated a reduced toxicity as compared with previous studies, even if a higher dosage is used.
T146	76618-76746	Epistemic_statement	denotes	There are also recent clinical reports on the use of colistin in continuous intravenous infusion to minimise potential toxicity.
T147	76747-76907	Epistemic_statement	denotes	This reduction of toxicity without impairment of efficacy (concentration-dependent killing in in-vitro timekill studies) should be confirmed by further studies.
T148	77077-77237	Epistemic_statement	denotes	This highlights the urgent need to preserve this molecule by the best appropriate dose regimen and by an optimal synergistic combination with other antibiotics.
T149	77560-77773	Epistemic_statement	denotes	The emergence of infections caused by bacteria resistant to almost all antimicrobial agents may have renewed the interest for addressing the contributions, limitations and future clinical indications of this drug.
T150	78454-78684	Epistemic_statement	denotes	The disodium salt of fosfomycin can be administered intravenously in high doses due to its very low toxicity, achieving plasmatic peak levels that are several times above the MIC of susceptible microorganisms (breakpoint 64 g/mL).
T151	79035-79186	Epistemic_statement	denotes	As a counterbalance, fosfomycin can act synergistically with other antibiotics, especially with those that inhibit later points in cell-wall synthesis.
T152	79187-79336	Epistemic_statement	denotes	Such synergism has been shown repeatedly against different strains of Staphylcoccus aureus, CNS, Streptococcus pneumoniae and Pseudomonas aeruginosa.
T153	79614-79775	Epistemic_statement	denotes	However, the reported clinical experience with these combinations is very scarce and, therefore, there are not evidence-based recommendations supporting its use.
T154	79776-80062	Epistemic_statement	denotes	On the other hand, various clinical trials have indicated that fosfomycin trometamol, as a sole antibiotic, is effective and safe for the treatment of uncomplicated UTI, providing high and long lasting urinary fosfomycin levels, which help to prevent the emergence of resistant strains.
T155	80205-80318	Epistemic_statement	denotes	of fosfomycin trometamol may be considered nowadays as a first line therapy for uncomplicated UTI in young women.
T156	80319-80452	Epistemic_statement	denotes	However, the possible emergence of fosfomycin-resistant mutants among ESBL-producing enterobacteriaceae should be taken into account.
T157	80612-80838	Epistemic_statement	denotes	Combinations of iv fosfomycin with other antibiotics may be considered in selected cases, but whether these combinations yield improved outcomes in specific infections due to multirresistant pathogens remains to be determined.
T158	80839-80993	Epistemic_statement	denotes	Logistic reasons and financial limitations will make difficult the realisation of appropriate prospective studies to answer this issue in the near future.
T159	81360-81780	Epistemic_statement	denotes	Chloramphenicol's loss of favour began in the 1960s, when it was shown to have two distinct toxic effects on hematopoiesis: a frequently observed, dose-dependent anaemia, reversible on cessation of therapy, and an irreversible, 'idiosyncratic' aplastic anaemia, which had an incidence of approximately 1 case per 30,000 courses of therapy, a high case fatality rate, and no correlation with the or duration of treatment.
T160	81945-82081	Epistemic_statement	denotes	Analogues of chloramphenicol have been developed that lack the aromatic NO 2 group that is thought to cause irreversible marrow aplasia.
T161	82082-82255	Epistemic_statement	denotes	Although the clinical efficacy of such compounds has not been evaluated, they are effective in vitro against most bacteria, even those that are resistant to chloramphenicol.
T162	82256-82414	Epistemic_statement	denotes	The data provided in support of a hypothesis that these molecules needed a nitro group in order to cause the blood dyscrasias were insufficient in themselves.
T163	82480-82669	Epistemic_statement	denotes	The potential for florfenicol to cause blood dyscrasias, such as aplastic anaemia, in humans was discussed in relation to the chemically related chemicals chloramphenicol and thiamphenicol.
T164	82670-82809	Epistemic_statement	denotes	Human epidemiological data could not be used to demonstrate the safety of florfenicol as florfenicol has never been used in human medicine.
T165	82810-83085	Epistemic_statement	denotes	Nevertheless, because there is as yet no way to monitor the potential for irreversible bone marrow toxicity, it is unlikely that such compounds will become available for the treatment of chloramphenicolresistant infections in general -and meningococcal disease in particular.
T166	83317-83501	Epistemic_statement	denotes	It would, however, be a very good thing if we could find a new drug or group of drugs that produced similar results in fighting infection but did not have as many serious side effects.
T167	83502-83632	Epistemic_statement	denotes	It would take a long time before any drug could ever replace chloramphenicol, because of both its broad use and its very low cost.
T168	83633-83768	Epistemic_statement	denotes	Tropical medicine: from basic science to field work O57 Evaluation of malaria status and immune response to Plasmodium falciparum MSP-2
T169	83769-83947	Epistemic_statement	denotes	Objectives of study: MSP-2 is a highly polymorphic 45−53 kDa merozoite surface antigen and very immunogenic malaria antigen, which is considered as a promising vaccine candidate.
T170	84054-84162	Epistemic_statement	denotes	Many studies have suggested a protective role for specific IgG antibodies against variable regions of MSP-2.
T171	84341-84512	Epistemic_statement	denotes	The association of haemoglobin and parasitaemia as two indicators of clinical malaria with acquired immunity were analysed to elucidate the pattern of protective immunity.
T172	85217-85490	Epistemic_statement	denotes	Increasing the age was negatively correlated with parasitaemia and positively with IgG antibody responses and haemoglobin levels indicating that total IgG responses to domains 2, 3 and crude schizont extract coincidental to a decrease in parasitaemia density and frequency.
T173	85761-86064	Epistemic_statement	denotes	Conclusion: IgG3 was the main antibody, mainly against domain 3 of MSP-2, that was associated with increase in haemoglobin levels and decrease in parasitaemia suggesting that domain 3 is preferred over other domains and crude schizont extract in presenting a clearer picture of immunity against malaria.
T174	86065-86246	Epistemic_statement	denotes	These results could be an evidence of protective role of these antibodies against malaria disease and, therefore, domains 3 can be considered as reliable vaccine candidate antigens.
T175	86315-86416	Epistemic_statement	denotes	Serosurveillance indicates that almost all native adults have been infected, mostly asymptomatically.
T176	86523-86711	Epistemic_statement	denotes	Even though some of its peer flaviviruses are known to reside persistently within the host and contribute to host illnesses, dengue virus has not been shown to behave in a similar fashion.
T177	87542-87684	Epistemic_statement	denotes	Demographic data of all patients were analysed, especially for the history of recent febrile illnesses which could be due to dengue infection.
T178	87685-87813	Epistemic_statement	denotes	Background: Intermittent preventive antimalarial treatment of infants (IPTi) is considered a promising malaria control strategy.
T179	87986-88055	Epistemic_statement	denotes	Studies modeling the effect of malaria incidences on IPTi are scarce.
T180	88056-88180	Epistemic_statement	denotes	The aim of this study was to describe how far protective efficacy of IPTi depends on the incidence rate of clinical malaria.
T181	89111-89323	Epistemic_statement	denotes	Interpretation : Correlations between IPTi efficacy and malaria incidences may have implications on IPTi implementation strategies I will discuss the role mathematical modelling in pandemic planning and response.
T182	89324-89498	Epistemic_statement	denotes	Recent research examining whether antiviral prophylaxis and social distance measures could be used to contain a nascent pandemic at its point of origin will then be reviewed.
T183	89499-89659	Epistemic_statement	denotes	Containment is potentially feasible, but requires rapid detection of the initial transmissible case cluster and a rapid and organised response to each new case.
T184	89660-89712	Epistemic_statement	denotes	These may be demanding criteria for much of SE Asia.
T185	89713-89872	Epistemic_statement	denotes	If containment fails, slowing spread becomes a policy priority and in that context I will discuss the potential impact of restrictions on international travel.
T186	90655-90880	Epistemic_statement	denotes	Apart from neutropaenic enterocolitis, a broad spectrum of infections associated with impairment of mucosal barriers may be clinically important, e.g., streptococcal bacteraemia, septic enterococcal infection, or candidaemia.
T187	91092-91212	Epistemic_statement	denotes	Primary removal of foreign material may be important for the successful management of these catheter-related infections.
T188	91213-91542	Epistemic_statement	denotes	Allogeneic hematopoietic stem cell transplantation with reducedintensity conditioning has become more common also for treatment of aggressive haematologic malignancies in elderly patients as well as in patients with severe co-morbidity, who formerly have not been taken into consideration for myeloablative transplant procedures.
T189	91543-91821	Epistemic_statement	denotes	Despite a marked reduction of complications related to pancytopenia combined with acute graft-versus-host reaction, the rate of severe and life-threatening fungal infections and cytomegalovirus diseases has turned out to be comparable to conventional allogeneic transplantation.
T190	91995-92353	Epistemic_statement	denotes	Tuberculosis: fast forward to new approaches S17 The broad introduction of monoclonal antibodies to CD20 and CD52 and of nucleoside analogs into the treatment of patients with B-or T-cell lymphomas has lead to long-term depletion of B cells, eventually associated with decreasing levels of serum immunoglobulins, and T-cell deficiency lasting for many years.
T191	92577-92759	Epistemic_statement	denotes	Targeted prophylaxis is warranted for selected patient groups, whereas high alertness and early pre-emptive antimicrobial intervention is mandatory in the majority of these patients.
T192	93146-93271	Epistemic_statement	denotes	However, this method is technically demanding and labour intensive, and requires weeks of culturing to obtain sufficient DNA.
T193	93272-93338	Epistemic_statement	denotes	The complex RFLP patterns are difficult to interpret and exchange.
T194	94386-94515	Epistemic_statement	denotes	The use of 15 selected loci is recommended as the new international gold standard for typing of M. tuberculosis complex isolates.
T195	94516-94628	Epistemic_statement	denotes	A recent study pointed out that VNTR typing on basis of 24 loci is useful to study the phylogeny of the complex.
T196	94629-94756	Epistemic_statement	denotes	As experienced after the standardisation of IS6110 RFLP typing in 1993, it is expected that the recent (December 2006; J. Clin.
T197	95259-95500	Epistemic_statement	denotes	Because in the epidemiology of tuberculosis transmission and manifestation of the disease can be separated in time by multiple years, the switch to VNTR typing can not be done without any overlap of the application of the two typing methods.
T198	95941-96037	Epistemic_statement	denotes	During these 6 months, such a case of TB is likely to infect, on the average, 10 close contacts.
T199	96038-96174	Epistemic_statement	denotes	If one of these 10 newly infected contacts then develops TB sometime in his life time, he will infect 10 other persons before diagnosis.
T200	96206-96321	Epistemic_statement	denotes	Thus, if a TB control programme is only focused on the treatment of active cases, TB will never come under control.
T201	96322-96520	Epistemic_statement	denotes	The fundamental question in TB control, therefore, is "can we predict who among the latently infected people will progress to active disease so that such a person can be given preventive treatment?"
T202	96521-96626	Epistemic_statement	denotes	To answer this question, the mechanism of Mtb persistence and reactivation needs to be better understood.
T203	96627-96700	Epistemic_statement	denotes	A variety of models for bacterial persistence has been proposed recently.
T204	96701-96901	Epistemic_statement	denotes	Most genetic studies that provide evidence for the putative role of a gene in persistence are based on demonstrating that an Mtb strain disrupted in such a gene is attenuated in an animal model of TB.
T205	96902-97027	Epistemic_statement	denotes	However, several recent gene disruption studies have shown that Mtb mutants can also become hypervirulent in an animal model.
T206	97028-97206	Epistemic_statement	denotes	This suggests that some Mtb genes may actually help to temper the virulence potential of Mtb so that the organism can establish a stable niche in a host without harming the host.
T207	97380-97610	Epistemic_statement	denotes	The operon appears to respond to a signal induced by the host's granuloma cell turnover, while the host's proinflammatory cells that comprise the granulomas appear to respond to the changing bacterial cell envelope lipid turnover.
T208	98029-98152	Epistemic_statement	denotes	This mutant is also hypervirulent but for an opposite reason-it causes rapidly progressive, hyper-proinflammatory response.
T209	98153-98342	Epistemic_statement	denotes	Thus, the mce1 operon appears to serve as a homeostatic regulator of pro-inflammatory response by the host, helping to establish a balanced relationship favourable to both the host and Mtb.
T210	98343-98614	Epistemic_statement	denotes	Understanding and exploiting this relationship may lead to new ways to predict a subset of latently infected people who progresses to active disease; it may also lead to the development of a therapeutic vaccine to prevent latently infected people from ever developing TB.
T211	99496-99679	Epistemic_statement	denotes	Objectives: Staphylococcus aureus can be a respiratory pathogen in cystic fibrosis (CF) and its pathogenicity is related to a combination of virulence and antibiotic-resistance genes.
T212	99680-99731	Epistemic_statement	denotes	Little is known about the agr-group in CF-isolates.
T213	100889-101257	Epistemic_statement	denotes	agrI was associated with the presence of many virulence-genes such as cytotoxins and proteases (sea-lukE-splB) and in one agrI isolate lukS/F-PVL was found; agrII also possessed an adhesin sdrE; agrIII was associated with adhesins and enterotoxin (fnbA-sea-cna), the exfoliatinA was never detected; agrIV possessed the cytotoxin lukE, adhesin cna and exfoliatinA, eta.
T214	101258-101394	Epistemic_statement	denotes	Protease gene (splB) was always found associated with cytotoxin lukE in agrI-II-III and, mostly, sdrE adhesin was associated with these.
T215	101395-101550	Epistemic_statement	denotes	A frequent inversecorrelation was found between cna and lukE-splB in all agr-groups and a close correlation was observed between cap8 and cna in agrIII-IV.
T216	101551-101945	Epistemic_statement	denotes	Conclusion: Our data demonstrated for the first time an increase of MRSA in our centre; furthermore, CF-persistent infections were not associated with a distinct agr-specificity group or a diffused antibioticresistance of the strains, but rather S. aureus isolates have a complex distribution and combination of virulence determinants which contribute to S. aureus pathogenicity in CF patients.
T217	103034-103184	Epistemic_statement	denotes	The increased proliferation of neural progenitors suggests that endogenous mechanisms may limit consequences of neuronal destruction after meningitis.
T218	103185-103287	Epistemic_statement	denotes	Stimulation of neurogenesis might help to improve therapy of acute inflammatory diseases of the brain.
T219	104393-104495	Epistemic_statement	denotes	Calorimetric detection of microbial growth may be more sensitive and rapid than blood culture systems.
T220	107432-107571	Epistemic_statement	denotes	The comparison of patient samples correlated with this by showing an increase of 59% in the rate of detection of MRSA following enrichment.
T221	107572-107858	Epistemic_statement	denotes	In conclusion enrichment has proven to dramatically increase the sensitivity and rate of detection of MRSA compared to direct culture alone and in order to ensure maximum sensitivity in the detection of MRSA enrichment should be employed as the method of choice in routine laboratories.
T222	107860-108167	Epistemic_statement	denotes	The limited additional help of the inflammatory markers CRP or PCT in bacteraemia prediction compared to a model of clinical assessment and routine laboratory information required for septic evaluation suggest the need for further justification of the use of these measurements in cost-constrained settings.
T223	108548-108717	Epistemic_statement	denotes	In addition, within the last two years an increasing number of community-acquired (CA)-MRSA could also be noted in the Netherlands, which represent an additional danger.
T224	109457-109639	Epistemic_statement	denotes	However, the majority of spa types on the German side were in concordance to the national epidemiological trend with spa t001, t002, t003, t004 and t032 as the most common spa types.
T225	109640-109838	Epistemic_statement	denotes	The spa type t044 -often associated with CA-MRSA in central Europe -was detected on both sides; 1% on the German and~15% on the Dutch side of the border, underlining the emerging problem of CA-MRSA.
T226	110093-110148	Epistemic_statement	denotes	However, cross-border spread of MRSA was also detected.
T227	110274-110379	Epistemic_statement	denotes	Objectives: The success of pandemic hospital-acquired MRSA clones may be due to high adhesive properties.
T228	110545-110689	Epistemic_statement	denotes	agr dysfunction is associated with overexpression of certain adhesins and seems to be responsible of the success of the CMRSA-3 clone in Canada.
T229	111302-111433	Epistemic_statement	denotes	The adhesin gene profile (bbp, can, eno, ebpS, fib, clfA, clfB, fnbA and fnbB) was determined with multiplex PCR for each isolates.
T230	112124-112263	Epistemic_statement	denotes	No correlation between the adhesive property and the absence of deltahaemolysin production was observed, both in MRSA and in MSSA isolates.
T231	112264-112462	Epistemic_statement	denotes	We demonstrated that adhesive properties onto HAECs of MRSA Lyon clone isolates was higher than that MSSA isolates, but was heterogeneous despite similar genetic background and adhesin gene profile.
T232	112463-112554	Epistemic_statement	denotes	This could be the result of overexpression of adhesins independently of an agr dysfunction.
T233	112726-112973	Epistemic_statement	denotes	The ST8-SCCmec IVa (or socalled USA-300) clone has been associated with community outbreaks, nosocomial transmission, and identified as the primary cause of skin and soft tissue infections (SSTI) presenting to Emergency Departments across the USA.
T234	114679-114803	Epistemic_statement	denotes	Whilst numbers remain small, the occurrence of community-based clusters and the death of one patient give cause for concern.
T235	117978-118077	Epistemic_statement	denotes	With cipro, 7 subjects were clinical successes, 2 were failures and for 3, the outcome was unknown.
T236	118078-118238	Epistemic_statement	denotes	The urine pathogen was eradicated in 10 and was unknown for 1 levo subject compared to eradicated in 7, persisted in 3, and unknown in 2 cipro-treated subjects.
T237	118466-118521	Epistemic_statement	denotes	The outcome for the cipro-resitant E. coli was unknown.
T238	119577-119763	Epistemic_statement	denotes	MRSA infections appeared to be more common in patients who were younger, of Black racial origin, and in those with a major abscess compared with patients with infections not due to MRSA.
T239	119879-119959	Epistemic_statement	denotes	Yet, the prevalence of microbial resistance to aminoglycosides has remained low.
T240	120561-120743	Epistemic_statement	denotes	We conclude that each of the three major clones can readily be demarcated from other A. baumannii members, and that molecular diagnostics could be developed to identify them rapidly.
T241	120744-121034	Epistemic_statement	denotes	Analysis of the recombination/mutation rate shows that nucleotides do not change by recombination more frequently than by mutation, showing that recombination is unlikely to disrupt the clonal frame of the clones, which can therefore be expected to be stable over very long periods of time.
T242	121205-121318	Epistemic_statement	denotes	Therefore, there is a critical need to understand the correspondence between types produced by different methods.
T243	121319-121537	Epistemic_statement	denotes	This may be useful not only for the comparison of the genetic backgrounds of the particular set of isolates under study but also to produce a broader view of how the results of the different typing methods are related.
T244	121827-121969	Epistemic_statement	denotes	2006) and is now implemented in a free-access web-based interface, on which users can analyse their data anonymously and retrieve the results.
T245	122702-122844	Epistemic_statement	denotes	Based on these measures the users can quantitatively evaluate the discriminatory power of the typing methodologies used and their concordance.
T246	123008-123189	Epistemic_statement	denotes	This can be used to evaluate the predictive power of a typing methodology when compared to another, which can guide the user in the choice of a 'gold standard' for clone definition.
T247	123190-123354	Epistemic_statement	denotes	Furthermore, as new microbial typing methods are proposed, this methodology allows for their comparison in terms of type assignments with established methodologies.
T248	123355-123551	Epistemic_statement	denotes	Despite several case control studies and enhanced surveillance of both human cases and animal environmental isolates, there is still much unknown about the epidemiology of Campylobacter infection.
T249	124069-124209	Epistemic_statement	denotes	We describe here an analysis of the three year study data and steps taken to adapt the methodology for use in routine surveillance settings.
T250	124210-124418	Epistemic_statement	denotes	The study has demonstrated several interesting correlations between specific sequence types and a number of explanatory variables for disease (eg month of infection, locality of residence, and travel abroad).
T251	124419-124579	Epistemic_statement	denotes	Other studies provide increasing evidence of host-association for specific MLST types of campylobacter and these findings are related to the three year dataset.
T252	124580-124778	Epistemic_statement	denotes	In addition, many new types have been described in surface waters from this project and there is evidence for a distinct water-borne population that has not so far been described in human infection.
T253	125154-125230	Epistemic_statement	denotes	-In some place typical rickettsioses could be caused by different organisms.
T254	125231-125360	Epistemic_statement	denotes	In such cases, the new Rickettsia was misdiagnosed with a previously identified bacterium (such as R. massiliae with R. conorii).
T255	125508-125633	Epistemic_statement	denotes	These findings challenge the old dogma postulating that of one tick borne rickettsiosis was prevalent in one geographic area.
T256	125842-126006	Epistemic_statement	denotes	R. felis, a flea-transmitted spotted fever, and R. parkeri, a tick-transmitted spotted fever, have been shown since to infect human beings in the USA and in Urugay.
T257	126071-126163	Epistemic_statement	denotes	Many Rickettsia have been identified in ticks but have not been currently found in patients.
T258	126164-126223	Epistemic_statement	denotes	These Rickettsiae should be considered potential pathogens.
T259	126224-126312	Epistemic_statement	denotes	These new findings should stimulate investigations to identify new rickettsial diseases.
T260	126313-126390	Epistemic_statement	denotes	Patients with atypical rash or fever after arthropod bite should be targeted.
T261	126504-126612	Epistemic_statement	denotes	Can pharmacokinetic-pharmacodynamic parameters drive dosing regimens that are less vulnerable to resistance?
T262	126727-126730	Epistemic_statement	denotes	Pro
T263	126731-127012	Epistemic_statement	denotes	In recent years, the rules for selection of antimicrobial agents have been undergoing critical revision in terms of optimum dosing for control of infectious diseases, with the goal of potentiating treatment efficacy and reducing the risk of selecting multidrug resistant pathogens.
T264	127013-127295	Epistemic_statement	denotes	The most important criterion for rational choice of an antimicrobial agent is defined by its pharmacodynamic (PD) characteristics, and thus its antimicrobial activity which can be summarised as the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC).
T265	127296-127676	Epistemic_statement	denotes	The second criterion for selecting an antibiotic is due to its pharmacokinetic (PK) characteristics, since it has been demonstrated that antibiotic concentrations at the infection site influence the intensity and duration of the effect, and together with the PD parameters, provide a general inter-relationship and contribute to defining the potential clinical efficacy of a drug.
T266	127866-128028	Epistemic_statement	denotes	Moreover, the principles that link concentrations of antibiotics in humans and their effects have been outlined in order to determine the optimal dosing interval.
T267	128095-128234	Epistemic_statement	denotes	the newer quinolones and aminoglycosides, should be administered as a single daily dose to maximise the peak serum concentration/MIC ratio.
T268	128304-128586	Epistemic_statement	denotes	Existing data on fluoroquinolones suggest that a ratio of 100-125 correlates with high bacterial eradication and optimal clinical outcome in infections due to Gram-negative pathogens, while a ratio of 50 is associated with a high probability of eradication of S. pneumoniae strains.
T269	128587-128870	Epistemic_statement	denotes	For this group of antibiotics the new concept of the so called mutant prevention concentration (MPC) and mutant selection window (MSW) may be helpful in restricting the enrichment of mutant subpopulations and consequently, at least partially, in controlling the spread of resistance.
T270	128871-129107	Epistemic_statement	denotes	Beta-lactams, having time-dependent efficacy, usually do not have great post antibiotic effects (PAEs), and the parameter which seems to better correlate PD with PK is the time duration with concentrations higher than the MIC (T > MIC).
T271	129278-129723	Epistemic_statement	denotes	In summary, we can theoretically optimise the dosage regimen of antibiotics (dose, administration route and interval between doses) in clinical practice by correlating the PK and PD pertaining to each antibiotic class, based on experimental animal studies and these PK/PD parameters may contribute to the containment of resistance for all drug classes and especially the most important ones used in serious infections in intensive care patients.
T272	130491-130774	Epistemic_statement	denotes	In low-resource countries, effective surveillance programmes are difficult to implement for a number of reasons, including scarce financial resources, lack of laboratory facilities and, where laboratories do exist, lack of quality control, reliable reagents and adequate supervision.
T273	130775-130919	Epistemic_statement	denotes	In these settings, the development of reliable and low-cost alternative methods could facilitate the implementation of large-scale surveillance.
T274	131080-131398	Epistemic_statement	denotes	This bacterial population, although not being a specific target, is continuously exposed to the selective pressure generated by antimicrobial chemotherapy and may become a potential reservoir of resistant strains that can cause infections, and of resistance determinants that can be transferred to pathogenic bacteria.
T275	131399-131641	Epistemic_statement	denotes	Therefore, surveillance of antibiotic-resistant bacteria carried by healthy individuals is considered an indicator of the spread of antibiotic resistance that could also be useful to predict the emergence of resistance in pathogenic bacteria.
T276	131642-131821	Epistemic_statement	denotes	In this perspective, resistance patterns of some members of the commensal microbiota, such as the faecal Escherichia coli, have been evaluated in various epidemiological settings.
T277	132513-132669	Epistemic_statement	denotes	Many susceptibility testing methods recommended the use of ESBL screening and confirmation tests on a routine basis, including CLSI, BSAC, CA-SFM, and SRGA.
T278	132670-132743	Epistemic_statement	denotes	However, a number of issues have emerged with routine use over the years:
T279	132744-132746	Epistemic_statement	denotes	1.
T280	132747-132847	Epistemic_statement	denotes	The problem of defining an adequate number of substrates to ensure sufficiently sensitive screening.
T281	132848-133054	Epistemic_statement	denotes	Ideally, one should include a minimum of 4, namely cefpodoxime, ceftazidime, ceftriaxone or cefotaxime, and aztreonam, and at concentrations that often differ from those used for susceptibility breakpoints.
T282	133159-133343	Epistemic_statement	denotes	Some of these species have been shown to be important reservoirs for ESBLs, and resistance to extended-spectrum cephalosporins cannot solely attributed to stable de-repression of AmpC.
T283	133600-133756	Epistemic_statement	denotes	Such strains have been shown to harbour OXA enzymes, inhibitor-resistant TEM enzymes, or particularly plasmid-borne AmpC enzymes with significant frequency.
T284	133757-133967	Epistemic_statement	denotes	Thus there is no current phenotypic or genotypic test that can be practically and effectively applied in the routine laboratory with sufficient sensitivity to detect the emerging range of transmissible enzymes.
T285	133968-134079	Epistemic_statement	denotes	However, we can rely to a great extent on the selection of or change to appropriate susceptibility breakpoints.
T286	134080-134269	Epistemic_statement	denotes	A range of recent studies has suggested that failures of treatment with extendedspectrum cephalosporins are likely when strains of Enterobacteriaceae have MICs elevated above the wild-type.
T287	134270-134579	Epistemic_statement	denotes	Further, application of pharmacokinetic/pharmacodynamic (PK/PD) principles to the most widely recommended dosing schedules of cephalosporins suggest that the susceptibility breakpoints recommended by many methods are too high, and should to lowered to values that fortunately coincide wild-type cutoff values.
T288	134580-134919	Epistemic_statement	denotes	Hence, lowering of susceptibility breakpoints for extendedspectrum cephalosporins to those defined by PK/PD will indicate the presence of an ESBL or plasmid-borne AmpC enzyme with sufficiently high likelihood to allow laboratories to report both resistance to these agents and provide advice about appropriate infection control procedures.
T289	134920-135120	Epistemic_statement	denotes	Objectives: Since antibiotic resistance often is associated with a biological fitness cost for bacteria it is assumed that a reduction of antibiotic use is followed by a reduction in resistance rates.
T290	135323-135541	Epistemic_statement	denotes	So far no prospective intervention in the community has been carried out to investigate whether a substantial decrease of the use of a single antibiotic will result in a corresponding decrease in antibiotic resistance.
T291	136673-136802	Epistemic_statement	denotes	Resistance to NIT and MEC did not increase despite the substantial increase in the use of these drugs, 31% and 69%, respectively.
T292	137207-137304	Epistemic_statement	denotes	Whether the increase in FQ-resistance was related to the increase in use remains to be evaluated.
T293	138195-138266	Epistemic_statement	denotes	The main goal is to preserve the effectiveness of antimicrobial agents.
T294	138983-139128	Epistemic_statement	denotes	Although the epidemic spread in southern Sweden of penicillin-resistant S. pneumoniae was curbed, the national frequency increased from 4% to 6%.
T295	139129-139221	Epistemic_statement	denotes	A hospital outbreak of MRSA could be terminated using aggressive infection-control measures.
T296	139449-139630	Epistemic_statement	denotes	Despite this, antibiotic resistance in several bacterial species is slowly increasing which calls for continued sustained efforts to preserve effectiveness of available antibiotics.
T297	141853-141994	Epistemic_statement	denotes	There is limited variation in the use of different antibiotic groups in most hospitals -a risk factor for emergence of antibiotic resistance.
T298	142588-142847	Epistemic_statement	denotes	The four scales were: attitudes towards appropriateness of self-medication with antibiotics for bronchitis, beliefs about antibiotics for minor ailments, attitudes towards situational use of antibiotics and knowledge about antibiotics and viruses or bacteria.
T299	142923-143211	Epistemic_statement	denotes	Analysis: To deal with the possible confounding effect of both use of selfmedication and education, we performed stratified analyses, i.e., we studied the differences between countries separately for users and non-users of self-medication, and for respondents with high and low education.
T300	143454-143535	Epistemic_statement	denotes	To limit this increase the appropriate use of ciprofloxacin should be encouraged.
T301	145739-145942	Epistemic_statement	denotes	There was a trend towards a greater rise in creatinine in Group 2 versus Group 1: final creatinine increased by 88% vs 52% from baseline (p = 0.08), which was reversible on stopping study drug treatment.
T302	147882-148050	Epistemic_statement	denotes	Clinicians should be aware that C. gattii can be acquired in Canada and that the epidemiological and clinical characteristics of this disease differ from C. neoformans.
T303	148051-148193	Epistemic_statement	denotes	Objectives: The incidence of invasive zygomycosis (IZ) appears to be increasing, especially in patients treated for haematological malignancy.
T304	148194-148363	Epistemic_statement	denotes	Presently, no biological markers exsist that facilitate early diagnosis, and one has to rely on conventional diagnostic methods, such as culture, which lack sensitivity.
T305	149633-149756	Epistemic_statement	denotes	Conclusion: zAg and zygomycete DNA are present in BALF of patients with IZ, and might be a useful tool for early diagnosis.
T306	149757-149933	Epistemic_statement	denotes	The presence of both markers in BALF samples from high-risk patients without a clinically manifest disease might indicate the presence of colonisation or subclinical infection.
T307	150017-150080	Epistemic_statement	denotes	However, differences were detected between the different media.
T308	151004-151139	Epistemic_statement	denotes	Simultaneously with the increased expression of gapB, PIA production could be visualised through CLSM in sessile bacteria in all media.
T309	151375-151600	Epistemic_statement	denotes	The persistent expression of gapA in sessile bacteria could indicate a role in biofilm formation, especially in the early stages, while expression levels of gapB could indicate a role in the later phases of biofilm formation.
T310	151601-151727	Epistemic_statement	denotes	Results of gene expression and CLSM indicate a link between gapB and PIA production that is influenced by both Fe and glucose.
T311	151852-152026	Epistemic_statement	denotes	Purportedly, the uropathogenicity of S. saprophyticus can be attributed to its ability to cope with the high range of variation in salt-and urea-concentration in human urine.
T312	152027-152104	Epistemic_statement	denotes	The aim of this study was to elucidate virulence factors of uropathogenicity.
T313	152882-153041	Epistemic_statement	denotes	The biofilm formation in S. saprophyticus seems independent of agr-, Ssp-, SdrI, since no difference between knockout mutants to wild type strain was observed.
T314	153042-153111	Epistemic_statement	denotes	Conclusion: Bacterial aggregation could be due to increased adhesion.
T315	153112-153178	Epistemic_statement	denotes	The lipase activity may modulate hydrophobicity and Ca 2+ binding.
T316	153179-153300	Epistemic_statement	denotes	Higher local Ca 2+ concentration, as well as strengthened bacterial aggregation, may lead to increased crystal formation.
T317	153301-153395	Epistemic_statement	denotes	Bacteria may adhere to crystals, additionally to the later mechanism due to biofilm formation.
T318	153475-153527	Epistemic_statement	denotes	This may be a new model of infectious stone genesis.
T319	153528-153767	Epistemic_statement	denotes	This study strongly suggest that S. saprophyticus wild-type strain CCM 883 lacks important virulence factors in contrast to wild-type strain 7108 and biofilm formation may play an important role in S. saprophyticus urinary tract infection.
T320	153768-153981	Epistemic_statement	denotes	Objectives: The influence of biofilm formation in catheter-related candidiasis has been established and it has been shown that the development of biofilm by the colonising yeasts confers resistance to antifungals.
T321	154140-154239	Epistemic_statement	denotes	Methods: An in vitro model of C. albicans biofilm associated with 100% silicone catheters was used.
T322	155006-155223	Epistemic_statement	denotes	Conclusions: These preliminary results suggest that this new molecule, naturally produced within yeasts communities, could be a good candidate for the prevention of biofilms associated with indwelling medical devices.
T323	155523-155654	Epistemic_statement	denotes	Its immunogenicity and specificity led to a series of studies to assess its potential as a major component of new diagnostic tests.
T324	156126-156263	Epistemic_statement	denotes	It is clear that these tests are not confounded by prior BCG vaccination and are probably not subject to boosting by injected tuberculin.
T325	156264-156363	Epistemic_statement	denotes	Their quantitative readouts may also provide important information with respect to infectious load.
T326	156364-156600	Epistemic_statement	denotes	However, some findings have caused concern: disparity in test performance between temperate non-TB endemic and tropical TB-endemic settings, evidence of relatively poor sensitivity to the presence of certain M. tuberculosis strains (eg.
T327	156646-156719	Epistemic_statement	denotes	Pulmonary TB, certain TB contacts), and rapid unexplained test reversion.
T328	156720-156944	Epistemic_statement	denotes	It is therefore becoming clear that T cell assays may have a niche in the diagnosis of certain TB cases and in certain individuals suspected of having M. tuberculosis infection, but this niche has not yet been fully defined.
T329	156945-157056	Epistemic_statement	denotes	More longitudinal studies, especially following TB case contacts for the development of disease, are indicated.
T330	157057-157116	Epistemic_statement	denotes	Also more studies should be undertaken in TB endemic areas.
T331	157117-157241	Epistemic_statement	denotes	Finally, if these tests are to have any role in TB control globally they would need to be much cheaper and more easy to use.
T332	157315-157474	Epistemic_statement	denotes	Over the last ten years unprecedented progress has been made in the treatment of HIV infection by the application of combination antiretroviral therapy (cART).
T333	157767-157856	Epistemic_statement	denotes	During the last year a whole bundle of drugs with new targets has been studied in humans.
T334	158052-158170	Epistemic_statement	denotes	It is expected, that integrase inhibitors and CCR5-antagonists will be introduced into clinical practice in 2007/2008.
T335	158578-158675	Epistemic_statement	denotes	Preliminary data also suggest a high virological potency of the drug in treatment naïve patients.
T336	158860-159060	Epistemic_statement	denotes	Vicriviroc together with OBT has shown superiority over OBT alone in treatment experienced patients, but has failed in a phase II study in treatment naïve patients presumably due to matters of dosing.
T337	159061-159152	Epistemic_statement	denotes	Further studies to define the optimal dose (together with ritonavir boosting) are underway.
T338	159529-159660	Epistemic_statement	denotes	Since these drugs seem to be very well tolerated there is also a potential for their use in treatment naïve patients in the future.
T339	159820-159971	Epistemic_statement	denotes	Current antiretroviral regimens however cannot achieve virus eradication and virological rebound virtually always occurs after therapy discontinuation.
T340	159972-160072	Epistemic_statement	denotes	Long-term highly active antiretroviral therapy (HAART) is life saving, but poses several challenges.
T341	160073-160198	Epistemic_statement	denotes	Potential adverse events can be categorised as problems related to adherence, pharmacokinetics, toxicity and drug resistance.
T342	160199-160502	Epistemic_statement	denotes	Various interventions have been explored to improve and maintain good adherence among treated individuals, ranging from treatment simplification strategies to addressing mental health problems, and a major challenge is related to the need for integrated biomedical, social and behavioural interventions.
T343	160503-160610	Epistemic_statement	denotes	Inadequate adherence however accounts for only a subset of subtherapeutic drug levels in clinical practice.
T344	160611-160810	Epistemic_statement	denotes	There is a significant degree of inter-individual variability in absorption, metabolism and cellular transport of antiretroviral drugs, with potential impact on both efficacy and toxicity of therapy.
T345	160897-161017	Epistemic_statement	denotes	Although evidence of the influence of pharmacogenomics is growing, there remain limited data to guide clinical practice.
T346	161018-161232	Epistemic_statement	denotes	Proton pump inhibitors are an example of commonly prescribed medications that can affect antiretroviral drug levels by reducing the absorption of certain protease inhibitors (PIs) and increasing exposure to others.
T347	161233-161366	Epistemic_statement	denotes	Herbal medicines such as St. John's wort, widely used by HIV patients, also have the potential to interact with antiretroviral drugs.
T348	161367-161497	Epistemic_statement	denotes	Thus, patient education and good communication across care providers are paramount to prevent unfavourable drug-drug interactions.
T349	161498-161648	Epistemic_statement	denotes	The risk of toxicity associated with long-term antiretroviral therapy is difficult to predict reliably in an aging population of HIV-infected persons.
T350	161924-162159	Epistemic_statement	denotes	The risk of cardiovascular disease is a particular concern, due to the combined effects on the cardiovascular system of HIV infection, HAART and lifestyle related risk factors such as smoking which are common among HIVinfected persons.
T351	162387-162488	Epistemic_statement	denotes	However, drug resistance continues to emerge as a result of problems with adherence and tolerability.
T352	162794-162923	Epistemic_statement	denotes	New drugs and drug classes are required to optimise treatment among drug-experienced persons and reduce the risk of side effects.
T353	163183-163281	Epistemic_statement	denotes	In spite of these concerns however, the benefits of HAART far outweigh the risk of adverse events.
T354	163282-163418	Epistemic_statement	denotes	The results strongly suggest that keratinocytes are able to produce cytokines in response to L. major stimulation through in part-TLR-2.
T355	163419-163774	Epistemic_statement	denotes	Aspergillus fumigatus, a termotolerant saprophyte, is associated with a wide spectrum of diseases in humans, that includes saprophytic colonisation of preexisting cavities, allergic asthma, allergic bronchopulmonary aspergillosis occurring as a complication of bronchial asthma or cystic fibrosis, and invasive aspergillosis in immunocompromised patients.
T356	163915-164156	Epistemic_statement	denotes	The inherent resistance to diseases caused by A. fumigatus suggests the occurrence of regulatory mechanisms that provide the host with adequate defence without necessarily eliminating the fungus or causing unacceptable levels of host damage.
T357	165491-165651	Epistemic_statement	denotes	These studies will illustrate how studying the structure and function of these molecules is increasing our understanding of virus pathogenesis and cell biology.
T358	165890-166025	Epistemic_statement	denotes	The complex situation of malaria transmission in various endemic areas requires differentiated recommendations for malaria prophylaxis.
T359	166080-166219	Epistemic_statement	denotes	Malaria risk can be reduced by compliant exposure prevention, and with chemoprophylactic drugs for travel to high risk areas are available.
T360	166442-166502	Epistemic_statement	denotes	The importance of exposure prophylaxis should be emphasized.
T361	166503-166607	Epistemic_statement	denotes	It is recommended to use mosquito repellents after dusk, especially if outdoor activities are performed.
T362	166608-166717	Epistemic_statement	denotes	Light-coloured, loose-fitting insecticide-treated clothing with long trousers and long sleeves are suggested.
T363	166718-166862	Epistemic_statement	denotes	Sleeping under insecticide treated bed nets or in airconditioned rooms which are pre-treated with insecticides (knockdown spray) is recommended.
T364	166863-166914	Epistemic_statement	denotes	Chemoprophylaxis is recommended in high risk areas.
T365	167038-167162	Epistemic_statement	denotes	In German speaking countries, emergency treatment is recommended for trips to regions with low or intermediate malaria risk.
T366	167163-167267	Epistemic_statement	denotes	This strategy is recommended when the infection risk is lower than the risk of severe drug side effects.
T367	167540-167729	Epistemic_statement	denotes	The guidelines for the application of the emergency-self-treatment should be discussed thoroughly with the traveller, to make sure that in case of fever the correct action will be taken: 1.
T368	167730-167918	Epistemic_statement	denotes	In case of fever (sudden onset or rapidly progressive) -axillary temperature >37.5ºC (oral, tympanal or rectal >38ºC) -a doctor should be seen and a malaria blood test should be performed.
T369	167973-168100	Epistemic_statement	denotes	If no doctor can be seen within 24h and the traveller is in an endemic region for at least 6 days, the fever should be lowered.
T370	168104-168184	Epistemic_statement	denotes	The malaria emergency medication should be taken with adequate amounts of fluid.
T371	168188-168302	Epistemic_statement	denotes	In every case, also after the intake of the malaria drug a doctor must be consulted at the earliest possible time.
T372	169059-169192	Epistemic_statement	denotes	The initially asymptomatic liver disease is still rare in Central Europe, and diagnosis is often made at a late stage of the disease.
T373	169618-169714	Epistemic_statement	denotes	However, the expertise of the radiologist is often not available due to the low incidence of AE.
T374	169715-169788	Epistemic_statement	denotes	Serology is helpful, but may be misleading due to non-standardised tests.
T375	170074-170179	Epistemic_statement	denotes	Filarial worm infections of humans cause morbidity and even death in developing countries of the tropics.
T376	170303-170487	Epistemic_statement	denotes	Another problem with controlling filarial infections is the lack of any alternative drugs that can be used in the current mass drug administration programmes should resistance develop.
T377	170913-171118	Epistemic_statement	denotes	Targeting of Wolbachia with antirickettsial drugs has lead to the recommendation of doxycycline for use on an individual basis and may be recommended in areas where resistance to current drugs may develop.
T378	171285-171469	Epistemic_statement	denotes	Research is underway to discover new drugs, preferably those already approved for use in humans, that have antiwolbachial activity and work in a shorter time and are widely applicable.
T379	173194-173317	Epistemic_statement	denotes	However, while the vegetation counts of the parent increased at 48, 72 and 120 h, the counts of GISA M1V16 remained stable.
T380	173518-173583	Epistemic_statement	denotes	This might explain its clustering in immuno-compromised patients.
T381	173584-173708	Epistemic_statement	denotes	Whether a very prolonged exposure to glycopeptides might restore pathogenicity and fitness defects remains to be determined.
T382	174079-174396	Epistemic_statement	denotes	In order to investigate whether the declined ability of the PFGEidentical isolates to form biofilm in vitro correlated to pathogenicity in vivo, 5 non-mucoid clones from 1980 and 1988 (early clones), and 1997, 1999 and 2003 (late clones) embedded in alginate were installed in the lungs of five groups of BALB/c mice.
T383	175837-176022	Epistemic_statement	denotes	While the exact mechanism remains to be fully elucidated, this demonstrates the validity of using commensal lactic acid bacteria strains in the prevention of gastrointestinal infection.
T384	176119-176470	Epistemic_statement	denotes	While the probiotics examined in this study are of obvious interest to those involved in the pig production industry, the similarities between the pig and human gastrointestinal tracts suggest that the probiotics offer potential in cases of human salmonellosis, given that the methodology used is also likely to be applicable to human disease control.
T385	176597-176710	Epistemic_statement	denotes	Such resistances have frequently been associated with strains that produce extendedspectrum b-lactamases (ESBLs).
T386	176711-177001	Epistemic_statement	denotes	As Salmonella with resistance to quinolone antimicrobials have become increasingly common in isolates from humans in England and Wales, a study has been initiated to investigate the occurrence of such genes in isolates from humans and food, and to assess their importance for public health.
T387	177652-177956	Epistemic_statement	denotes	Of these the isolates of Stanley and Typhimurium were from patients infected abroad, the isolate of Virginia was from a patient who had not travelled abroad, and the two isolates of Virchow, one from imported frozen chicken and one from a patient were associated with a series of infections in 2003/2004.
T388	178410-178548	Epistemic_statement	denotes	These results indicate that plasmidic quinolone resistance, often linked to other resistances, has now appeared in S. enterica in Britain.
T389	178549-178653	Epistemic_statement	denotes	This is of particular concern for the treatment of infections with invasive serovars such as S. Virchow.
T390	178654-178813	Epistemic_statement	denotes	Objective: The rapid characterisation of (drug-resistant) Mycobacterium tuberculosis (MTB) would be useful for the research and treatment of tuberculosis (TB).
T391	178814-178963	Epistemic_statement	denotes	Many important genetic markers of MTB have been identified, notably for drug resistance, but also genotype, bacterial lineage and adaptive potential.
T392	178964-179046	Epistemic_statement	denotes	A single assay allowing identification of these markers would aid control efforts.
T393	179288-179524	Epistemic_statement	denotes	We explored the utility of MLPA as a screening tool to rapidly characterise MTB-strains Method: MLPA can identify multiple single nucleotide polymorphisms (SNPs) by amplification of sequence-specific MLPA-probes, rather than target DNA.
T394	180200-180310	Epistemic_statement	denotes	To determine the predictive value of MTB-specific MLPA, we screened DNA of MTB-strains with unknown genotypes.
T395	180349-180440	Epistemic_statement	denotes	There was a very high correlation between sequencing results and results obtained via MLPA.
T396	180571-180725	Epistemic_statement	denotes	We have shown that with MTB-specific MLPA it is possible to identify drug resistance associated mutations and MTB lineage specific SNPs in a single assay.
T397	180726-180853	Epistemic_statement	denotes	Depending on the application, probes can be added to or removed from the probe-mix, making it a flexible, multi-purpose method.
T398	180854-180990	Epistemic_statement	denotes	MLPA products can be easily identified on an agarose-gel, making it especially suitable for screening of TB in the less-developed world.
T399	181381-181892	Epistemic_statement	denotes	Yet, there is a known disparity between fluoroquinolone-susceptible and -resistant isolates, which it is assumed has arisen from the susceptible population: Only a small proportion of resistant isolates belong to group B2, while the majority belong to group D. For a possible explanation of the disparate distribution among phylogenetic groups this work analysed ciprofloxacin-susceptible and -resistant ICU isolates in all phylogenetic groups for differences in virulence factors (VF) and mutation frequencies.
T400	182089-182327	Epistemic_statement	denotes	In order to compare isolates from different groups and susceptibilities, a similar and as large a number as possible of susceptible and resistant strains were chosen randomly from groups A (23; 27), B1 (7; 11), B2 (17; 9), and D (15; 25).
T401	182999-183172	Epistemic_statement	denotes	However, there was a small, but significant difference in the median of the mutation rates between the isolates of different groups, increasing in the order B2 < D < B1 < A.
T402	183351-183557	Epistemic_statement	denotes	Conclusion: Slightly, but significantly reduced mutation rates in strains of the deep rooted phylogenetic group B2 might be an explanation for their rare occurrence among fluoroquinolone-resistant isolates.
T403	183655-183820	Epistemic_statement	denotes	The aim of this study was to understand evolution of CAZ resistance among CAZ susceptible ESBL belonging to this cluster by step-wise in vitro selection experiments.
T404	184872-185035	Epistemic_statement	denotes	Interestingly, and with exception of two variants and CXM, a concomitant loss of resistance to all other antibiotics tested (antagonistic pleiotropy) was observed.
T405	185252-185330	Epistemic_statement	denotes	However, D240G change determined a lower decrease to FEP and CXM than P167S/T.
T406	185898-186018	Epistemic_statement	denotes	A77V could be a secondary mutation site affecting CAZ or could be involved in re-equilibrium of CTXR/CAZR co-resistance.
T407	186297-186536	Epistemic_statement	denotes	The new respiratory's FQs, levofloxacin (LEV) and moxifloxacin (MOX), retain their activity against these first-step parC mutants, although there are concerns that their widespread use might select for second-step, high-level FQ-R mutants.
T408	187609-187828	Epistemic_statement	denotes	However, an emm6 throat isolate, recovered from a 36-year old female in 2005, exhibited highlevel resistance to CIP (MIC 32 mg/mL), full resistance to LEV (MIC 8 mg/mL) and decreased susceptibility to MOX (MIC 1 mg/mL).
T409	190690-190865	Epistemic_statement	denotes	This will be an important prerequisite for definition of isolates as identical, related of different, which is essential for successful epidemiological outbreak investigation.
T410	191376-191511	Epistemic_statement	denotes	higher temperature, higher polymorphonuclear counts and complications are more frequent), but NTHi can still cause significant disease.
T411	191512-191677	Epistemic_statement	denotes	The role of NTHi in recurrent and non-responsive AOM in both infants and in older children is recognized, suggesting different biological pathways compared with Pnc.
T412	191904-191990	Epistemic_statement	denotes	The role of NTHi in LRIs in general, and in pneumonia in particular, is not yet clear.
T413	191991-192050	Epistemic_statement	denotes	In cystic fibrosis, however, NTHi is an important pathogen.
T414	192051-192344	Epistemic_statement	denotes	Although H. influenzae type b disease has practically been eliminated in vaccinated populations, the picture with S. pneumoniae in the 7-valent Pneumococcal Conjugate Vaccine (PCV7) era is much more complex owing to its limited serotype coverage and some replacement with nonvaccine serotypes.
T415	192345-192482	Epistemic_statement	denotes	A vaccine with additional pneumococcal serotypes and activity against NTHi would be a very welcome addition to our vaccine armamentarium.
T416	192483-192611	Epistemic_statement	denotes	Otitis media (OM) is a highly prevalent paediatric disease that is associated with significant morbidity and socioeconomic cost.
T417	192816-193043	Epistemic_statement	denotes	Despite their similar roles as opportunistic pathogens of the middle ear, the pathogenic mechanisms utilised by these bacteria (nontypeable Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis) are unique.
T418	193747-194049	Epistemic_statement	denotes	In the past few years it has been demonstrated that each of the three predominant bacteria involved in OM can form a biofilm in in vitro assay systems and in animal models, and that they participate in biofilms formed on middle ear mucosa specimens recovered from children with recurrent or chronic OM.
T419	194274-194586	Epistemic_statement	denotes	It is particularly intriguing that some of the paediatric middle ear mucosa-derived biofilms characterised were of mixed bacterial aetiology, suggesting that progress made on single-microbe directed strategies for the treatment and/or prevention of OM, while highly encouraging, are also likely to be inadequate.
T420	194587-194943	Epistemic_statement	denotes	Therefore, a significantly greater understanding of how microbial physiology relates to the involvement of biofilms in OM is required to identify points in the disease course that are perhaps more amenable to treatment strategies, and also biofilm-relevant antigenic targets that would be helpful in the rational design of vaccine candidates to prevent OM.
T421	195100-195259	Epistemic_statement	denotes	Evidence suggests that PD is involved in the pathogenesis of respiratory tract infections, and has been implicated in NTHi adhesion and invasion of host cells.
T422	195260-195529	Epistemic_statement	denotes	An isogenic PD-deficient NTHi-mutant, compared with the wild type strain, had an approximately 100-fold lower capacity to cause acute otitis media (OM) in rats and induced significantly less impairment of ciliary function in a human nasopharyngeal tissue culture model.
T423	195530-195747	Epistemic_statement	denotes	The likely mechanism of pathogenicity is that PD is an enzyme (glycerophosphodiester phosphodiesterase, GlpQ) that releases phosphorylcholine (ChoP) from host epithelial cells to the lipooligosaccharide (LOS) on NTHi.
T424	195748-195922	Epistemic_statement	denotes	LOS-ChoP interacts with platelet-activating factor receptors, inhibiting ciliary beat frequency of human bronchial epithelial cells and activating G protein-related pathways.
T425	196857-196977	Epistemic_statement	denotes	Large efficacy trials are not feasible any more, and the acceptance of the new PCVs will rely on immunogenicity studies.
T426	197256-197492	Epistemic_statement	denotes	The protective functional mechanism of antibodies to pneumococcal capsular polysaccharides resides in opsonophagocytosis and the demonstration of the opsonophagocytic activity (OPA) has been regarded as an important secondary threshold.
T427	197493-197605	Epistemic_statement	denotes	Thus far there are only few published PCV efficacy trials that connect with OPA data and their good correlation.
T428	197760-198012	Epistemic_statement	denotes	In general, the OPA titers and the antibody concentrations correlate well, but different serotypes can show various OPA/EIA ratios meaning that for certain serotypes (like 19F or 1) more antibodies are needed for killing the bacteria than for the rest.
T429	198013-198207	Epistemic_statement	denotes	Importantly, the elderly and HIV positive patients seem to have antibodies of low functional activity, and measuring OPA in studies in the elderly and HIV patients has been considered important.
T430	198400-198537	Epistemic_statement	denotes	Measuring OPA with the classical killing assay consumes serum and time and thus measuring OPA for large materials is not always feasible.
T431	198538-198680	Epistemic_statement	denotes	However, the development of multiplex and/or high throughput assays will end up in wider use of this technology in the future clinical trials.
T432	198681-198815	Epistemic_statement	denotes	This would be in concordance with the guidelines for evaluation meningococcal conjugate vaccines by serum bactericidal activity assay.
T433	199238-199651	Epistemic_statement	denotes	More than 90 serotypes of pneumococci exist, but only 10 serogroups appear to be responsible for 80-85% of invasive pneumococcal disease and pneumococcal otitis media (OM) worldwide, ranging from the relatively rare but clinically severe meningitis, to the more frequent infections of the bloodstream and the lungs, such as pneumonia and finally to the extremely common middle ear infections among young children.
T434	199652-199801	Epistemic_statement	denotes	Middle ear infections are often associated with diagnostic uncertainty, frequent use and misuse of antibiotics, and recurrent and persistent disease.
T435	199876-199992	Epistemic_statement	denotes	Recurrent and persistence disease can lead to temporary or even permanent hearing loss and surgery (tube placement).
T436	199993-200187	Epistemic_statement	denotes	In order to address these issues, preventive acute OM (AOM) strategies should include a vaccine with broader pneumococcal serotype coverage as well as protection against additional otopathogens.
T437	201234-201571	Epistemic_statement	denotes	Patients infected with 027 strain were likely to have a more severe disease (RR = 1.72, 95% CI: 1.07−2.75, p = 0.048), to have received less antimicrobials in the month preceding diarrhoea (RR = 0.76, 95% CI: 0.53−1.10, p = 0.05) and to have been more specifically treated by metronidazole or vancomycin (RR = 1.32, 1.17−1.49, p = 0.02).
T438	201779-201864	Epistemic_statement	denotes	The incidence and severity of nosocomial C. difficile disease seems to be increasing.
T439	202160-202247	Epistemic_statement	denotes	Described changes correlate with changed populations of C. difficile present in humans.
T440	202248-202471	Epistemic_statement	denotes	New type BI/NAP1/027 with increased virulence is spreading since 2003, but only part of the recent increase in mortality and morbidity caused by C. difficile infections can be accounted for by this new highly virulent type.
T441	202561-202750	Epistemic_statement	denotes	Such binary toxin positive strains used to be more often associated with animal than human host and early typing comparisons did not show many similarities between human and animal strains.
T442	202751-202900	Epistemic_statement	denotes	However, recent studies found a marked overlap between isolates from calves and humans, including two of the predominant outbreak types, 027 and 017.
T443	202901-203056	Epistemic_statement	denotes	C. difficile has also been found in retail meat samples, suggesting that food could be involved in the transmission of C. difficile from animals to humans.
T444	203429-203852	Epistemic_statement	denotes	The infection control measures include recommendations to isolate infected patient on a single room with designated toilet, to apply proper hand hygiene with soap and water, to use appropriate protective clothing (gloves and aprons or gowns), to intensify environmental cleaning with a chlorine containing disinfectant and to take specific precautions for the use of devices (disposable or dedicated to individual patient).
T445	203922-204051	Epistemic_statement	denotes	Each hospital should have an appropriate surveillance system to recognize an increase of the incidence of CDAD in an early stage.
T446	204052-204206	Epistemic_statement	denotes	All infection control measures should be written in a local protocol so that additional measures can be carried out as soon as a problem with CDAD arises.
T447	204207-204620	Epistemic_statement	denotes	When outbreaks occur, additional recommendations include a reinforcement of general and hand washing measures, intensifying of testing patients with diarrhoea for C. difficile, reinforcement of environmental cleaning, information and education of healthcare workers, cleaning department and visitors, cohorting of infected patients, and eventually closure of the unit followed by intensive environmental cleaning.
T448	204621-204736	Epistemic_statement	denotes	Restricted antibiotic prescribing is also highly recommended to reduce polypharmacy and duration of administration.
T449	204737-204876	Epistemic_statement	denotes	Second and third generations cephalosporins, clindamycin and more recently fluoroquinolones have been identified as potential risk factors.
T450	204877-205096	Epistemic_statement	denotes	Although some hospitals report successes for enhanced environmental cleaning with potentially effective agents such as hydrogen peroxide vapour, the evidence is too scarce to consider this as an evidence-based approach.
T451	205430-205516	Epistemic_statement	denotes	However, Acinetobacter infections can also be acquired outside the healthcare setting.
T452	205769-205918	Epistemic_statement	denotes	Most of the latter reports originate from tropical or sub-tropical areas, and may become more common following ongoing changes in the global climate.
T453	206228-206355	Epistemic_statement	denotes	A recent increase in the number of carbapenem-resistant strains, particularly in eastern Europe, is currently of great concern.
T454	206356-206620	Epistemic_statement	denotes	The recent EU-funded ARPAC study revealed that 130 of 169 participating European hospitals in 32 European countries had encountered carbapenem-resistant isolates of Acinetobacter, ranging from very rare sporadic resistant isolates to an endemic/epidemic situation.
T455	207050-207325	Epistemic_statement	denotes	Three 'European Clones' (lineages) have been identified in hospitals throughout Europe, but numerous other, more localised, clones have also been characterised, showing that the problem of A. baumannii is not confined solely to the widespread 'European clones I, II and III'.
T456	207326-207434	Epistemic_statement	denotes	The reasons why certain A. baumannii lineages are more successful than others are not understood at present.
T457	207435-207590	Epistemic_statement	denotes	Overall, the available epidemiological evidence suggests that A. baumannii is becoming one of the most significant microbial challenges of the current era.
T458	207591-207814	Epistemic_statement	denotes	Strains in some hospitals are already effectively untreatable, and more scientific efforts and resources are urgently needed to further elucidate the epidemiological and infection control issues related to these infections.
T459	207948-208124	Epistemic_statement	denotes	Whereas A. baumannii has itself a quite high level of naturallyoccurring antibiotic resistance, it may acquire additional resistance traits as a source of multidrug resistance.
T460	208125-208203	Epistemic_statement	denotes	These resistance mechanisms may involve most of the antibiotic molecules, i.e.
T461	208331-208445	Epistemic_statement	denotes	A similar trend between the number of A. baumannii infections and antibiotic resistance may be observed worldwide.
T462	209121-209310	Epistemic_statement	denotes	The patient's urine was tested positive for Lassa virus, which was taken into account for the risk assessment and contributed to the decision to trace back copassengers potentially exposed.
T463	210044-210224	Epistemic_statement	denotes	Our best estimate for the initial reproduction number (R 0 ) was 3.7, although it could range from 2 to 11 depending on assumptions regarding incubation and lifespan in mosquitoes.
T464	210225-210374	Epistemic_statement	denotes	In the best fitting case, each infected individual may have contaminated 3 mosquitoes at most, and each mosquito contaminated 1.4 persons on average.
T465	210375-210559	Epistemic_statement	denotes	Using data from the first season alone, modelbased extrapolations suggested that epidemic outbreaks were possible as long as more than one third of the population remained susceptible.
T466	210560-210795	Epistemic_statement	denotes	Conclusion: Despite a thousand-fold change in incidence between the two seasons, the transmission characteristics of Chikungunya were similar; therefore there is no epidemiological evidence for an increase in virulence between seasons.
T467	210796-210967	Epistemic_statement	denotes	At a time when information systems make it easier to monitor the course of emerging diseases, methods for timely and efficient analysis of the data must also be developed.
T468	212048-212185	Epistemic_statement	denotes	Further research is needed to determine sequelae, risk factors, outbreak potential, and the utility of chemoprophylaxis for this disease.
T469	212521-212721	Epistemic_statement	denotes	Previous studies with methicillin-resistant Staphylococcus aureus (MRSA) revealed that telavancin increases cell membrane permeability and causes rapid dissipation of the bacterial membrane potential.
T470	212865-212993	Epistemic_statement	denotes	Methods: Cell membrane potential and membrane permeability were studied in telavancin-treated S. aureus ATCC 33591 (MRSA) cells.
T471	212994-213117	Epistemic_statement	denotes	The fluorescent dyes, DiOC2(3) and propidium iodide, were used to assess membrane potential and permeability, respectively.
T472	213203-213334	Epistemic_statement	denotes	Results: Telavancin (MIC, 0.5 mg/mL) caused a concentration-and time-dependent dissipation of the membrane potential in MRSA cells.
T473	213769-214003	Epistemic_statement	denotes	Conclusion: Exposure of MRSA cells to telavancin initiated concentration-and time-dependent membrane depolarisation and increases in permeability, further demonstrating that telavancin interferes with bacterial cell membrane function.
T474	214603-214816	Epistemic_statement	denotes	In vitro studies suggest that TLV exhibits superior antibacterial potency relative to vancomycin (VAN); this may be due to the lipophilic decylaminoethyl side chain that targets TLV to the bacterial cell membrane.
T475	215153-215337	Epistemic_statement	denotes	Susceptibility or inducible resistance to oleandomycin was associated with the presence of an inducible erm(A) or erm(C) gene, respectively and might constitute markers of these genes.
T476	215338-215506	Epistemic_statement	denotes	The risk analysis for the clindamycin use in therapy of infections due to S. aureus inducibly resistant to erythromycin might include the nature of the resistance gene.
T477	219840-220009	Epistemic_statement	denotes	These data could provide further evidence about the possible role of pentapeptidic proteins of different Gram-positive species in their natural resistance to quinolones.
T478	220010-220110	Epistemic_statement	denotes	These Gram positives species could constitute a reservoir of Qnr-like quinolone resistance proteins.
T479	220301-220378	Epistemic_statement	denotes	However, it is unknown whether loss of K + is sufficient to cause cell death.
T480	220379-220526	Epistemic_statement	denotes	In this study we determined the kinetics of both cell death and lysis of S. aureus treated with DAP to establish any relationships between the two.
T481	222026-222188	Epistemic_statement	denotes	Conclusion: Our findings support the Silverman model for the mode of action of DAP and the hypothesis that it can cause rapid cell death without whole cell lysis.
T482	222189-222316	Epistemic_statement	denotes	We have, however, shown that cell lysis does occur over time, through both EM images and the leakage of large amounts of b-gal.
T483	222317-222482	Epistemic_statement	denotes	Our findings, while upholding the Silverman model, suggest that it is too simple to conclude that cell death is due only to loss of K + and membrane de-energisation.
T484	222483-222552	Epistemic_statement	denotes	The rapid loss of ATP would be an equally likely cause of cell death.
T485	222553-222944	Epistemic_statement	denotes	Objective: To study the effects of efflux pump inhibitors (CCCP and PAbN) on carbapenems in P. aeruginosa (Pa); to investigate the correlation between the resistance phenotypes and expression levels of efflux pumps of Pa and discuss the mechanism of different phenotypes in resistant Pa. By contrast, all the qnrA1-positive but blaVEB-1-negative isolates were negative for the A/C2 replicon.
T486	222945-223196	Epistemic_statement	denotes	These results clearly indicated that the genes encoding QnrA1 and VEB-1, when identified concomitantly in a given isolate, were always located on plasmids belonging to the same IncA/C2-incompatibility group that may vary in size and digestion pattern.
T487	223197-223291	Epistemic_statement	denotes	In addition, plasmids carrying the blaVEB-1 gene but lacking qnrA1 were also of the A/C2 type.
T488	223292-223472	Epistemic_statement	denotes	On the opposite, plasmids that were qnrA1-positive but blaVEB-1-negative were of distinct replicon types, suggesting independent acquisition of the qnrA gene on different plasmids.
T489	223473-223723	Epistemic_statement	denotes	Restriction pattern analysis of plasmid DNAs performed using the PstI endonuclease revealed that the blaVEB-1-positive plasmids exhibited different restriction profiles but also sharing common bands, likely corresponding to a common plasmid backbone.
T490	223724-223956	Epistemic_statement	denotes	Hybridisation performed with an A/C2-specific probe showed an identical signal revealing that the bands carrying the replication control region of the plasmids were of identical size, as expected with plasmids from the same lineage.
T491	223957-224100	Epistemic_statement	denotes	Conclusion: It is shown here that the IncA/C2 plasmid may be the main vehicle of the blaVEB-1 gene on which the QnrA1 determinant may be added.
T492	224101-224201	Epistemic_statement	denotes	Understanding these patterns will help to identify potential targets for public health intervention.
T493	224472-224731	Epistemic_statement	denotes	Using data obtained from a large test accuracy study into rapid detection of intrapartum GBS colonisation, the aims were to determine (1) the prevalence of vaginal and rectal GBS in labouring women, comparing standard culture to enrichment culture techniques;
T494	224732-225002	Epistemic_statement	denotes	(2) what proportion of women present with different risk factors; (3) how both culture positivity and risk factors correlate with the frequency of IAP administration; (4) baby colonisation rates with regard to maternal colonisation site and whether or not IAP was given.
T495	227906-228010	Epistemic_statement	denotes	The production of PVL seems to be the main factor that contributes to the course of acute osteomyelitis.
T496	229853-229958	Epistemic_statement	denotes	Conclusion: the present case shows that C-MRSA PVL-, tsst 1 might be associated with family transmission.
T497	229960-230107	Epistemic_statement	denotes	The prevalence of pathogenic Y. enterocolitica in Swiss pigs was high using PCR, however, the isolation rate was clearly lower than in German pigs.
T498	230408-230535	Epistemic_statement	denotes	The genetic diversity of ail-positive Y. enterocolitica in the pig tonsils collected from one Swiss slaughterhouse was limited.
T499	230536-230597	Epistemic_statement	denotes	T. van were significantly associated with the CDAD incidence.
T500	230818-230879	Epistemic_statement	denotes	Possibly, investigation at ward-level might correlate better.

T1

Epistemic_statement

denotes

The aim of the current study was to describe the largest database ever collected in France on SSI and to analyse a 6-year temporal trend.

T2

1079-1197

Epistemic_statement

denotes

In each ward, 200 consecutive surgery procedures should be included and patients followed up to 30 days after surgery.

T3

2437-2582

Epistemic_statement

denotes

Impact of the national policy on SSI incidence remains to be further evaluated, although encouraging results were evidenced for specific surgery.

T4

2769-2825

Epistemic_statement

denotes

Data on HAI surveillance in maternity units are lacking.

T5

5418-5556

Epistemic_statement

denotes

Considering that all French hospitals account for 465,494 beds, 41,276 [95% CI: 40,896-41,656] BBFE could have occurred in France in 2004.

T6

5641-5859

Epistemic_statement

denotes

Post-exposure prophylaxis (PEP) was prescribed to 4.5% of exposed personnel (vs. 5.8% in 2003 and 6.3% in 2002); this decrease may reflect the impact of April 2003 French recommendations, which reduced PEP indications.

T7

6138-6247

Epistemic_statement

denotes

Prevention through education and use of safety devices (such as blunt suture needles) may thus be a priority.

T8

7422-7487

Epistemic_statement

denotes

Skin antiseptics can prevent the contamination of blood cultures.

T9

9254-9351

Epistemic_statement

denotes

Objectives: The inanimate hospital environment can become contaminated with nosocomial pathogens.

T10

9352-9563

Epistemic_statement

denotes

Hydrogen peroxide vapour (HPV) decontamination has proven effective for the eradication of persistent environmental contamination but the rate of recontamination following HPV decontamination is largely unknown.

T11

11317-11537

Epistemic_statement

denotes

The questionnaire was composed of two parts: first part contained parameters for determination of sociodemographic properties and the second contained questions about evaluation of the knowledge about prevention from NI.

T12

11538-11685

Epistemic_statement

denotes

Questions were prepared by using the references about the subject and by the help of the executives of the cleaning staff firm and statistics unit.

T13

12186-12441

Epistemic_statement

denotes

Knowledge level was not associated with gender, educational status and duration of working as cleaning staff (p > 0.05) but mean knowledge level of the staff working in the clinics was found higher than staff working in administrative sections (p < 0.05).

T14

12685-12875

Epistemic_statement

denotes

58.8% thought that they could prevent themselves from NI by hand washing before and after cleaning process, 80.8% stated they obeyed handwashing rules and 90.4% stated that they used gloves.

T15

12939-13085

Epistemic_statement

denotes

Conclusion: Measurement of the level of the knowledge of the hospital cleaning staff may be beneficial for determination of the existing problems.

T16

13086-13188

Epistemic_statement

denotes

Periodical well-established educational programmes should be started to improve the current situation.

T17

13301-13422

Epistemic_statement

denotes

Rapid and sensitive screening methods for direct detection of MRSA are essential to limit further spread in the hospital.

T18

15955-16091

Epistemic_statement

denotes

However, recent studies indicate that the throat may be an additional important site of colonisation (Nilsson P. J Clin Microbiol 2006).

T19

17340-17437

Epistemic_statement

denotes

Additional cost can be avoided by pooling the specimens while maintaining the higher sensitivity.

T20

17438-17537

Epistemic_statement

denotes

Therefore, optimal screening for S. aureus should include swabs from both the nares and the throat.

T21

17538-17611

Epistemic_statement

denotes

This may be even more important if screening is focused on MRSA carriage.

T22

18753-19015

Epistemic_statement

denotes

Stopping the hypochlorite disinfection was associated with a sudden increase in clinical cases of MRSA from 10 to 25% over a 6 month period (p = 0.03), with levels approaching those seen prior to the start of the infection control programme in 2001 (see figure).

T23

19016-19142

Epistemic_statement

denotes

Conclusions: Stopping hypochlorite environmental disinfection was strongly associated with an increase in clinical MRSA cases.

T24

20787-20864

Epistemic_statement

denotes

vanC1 was linked to E. gallinarum, and vanC2 to E. casseliflavus as expected.

T25

21056-21190

Epistemic_statement

denotes

Whether persistence of these antibiotic resistant strains is due to selection by antibiotics or other agents deserves further studies.

T26

21723-21888

Epistemic_statement

denotes

Data from NORM-VET could form a basis for risk assessments and be a tool for targeting interventions and further to evaluate the effectiveness of such interventions.

T27

22283-22368

Epistemic_statement

denotes

Specific clinical isolates from the routine diagnostic have been included biannually.

T28

22369-22449

Epistemic_statement

denotes

The isolates have mainly been tested using a microdilution technique (VetMICTM).

T29

22839-23095

Epistemic_statement

denotes

Conclusion: Evaluation of the first six years of the programme has recognized that the relatively low number of isolates of each species and source included complicates the conclusions possible to draw from the data, especially evaluating trends over time.

T30

23096-23361

Epistemic_statement

denotes

Even though the run costs of the programme has been limited to a minimum, it is still useful for the purpose of monitoring antimicrobial resistance within a country as Norway, where the resistance problem in the animal and food sectors still is at a very low level.

T31

23475-23652

Epistemic_statement

denotes

However, the use of this source to perform risk assessments is limited as there still is a lack of even more specific data as for instance data on usage at animal or farm level.

T32

23653-23782

Epistemic_statement

denotes

O26 Comparison of antibiotic susceptibilities of Staphylococcus aureus and S. intermedius isolates from dog owners and their dogs

T33

23783-24008

Epistemic_statement

denotes

Objectives: Antibiotic resistance in veterinary isolates has been reported to be higher than in human isolates due to frequent empirical use, and there are concerns about transfer of resistance between staphylococcal species.

T34

24009-24122

Epistemic_statement

denotes

S. intermedius is the more common colonising species in dogs, but S. aureus, including MRSA, may also be present.

T35

24123-24207

Epistemic_statement

denotes

Case reports suggest there can be cross-infection between companion animals and man.

T36

24208-24359

Epistemic_statement

denotes

Increasing concern about MRSA in the community has led to recommendations for surveillance of antibiotic resistance in isolates from companion animals.

T37

26202-26306

Epistemic_statement

denotes

Veterinary use of antibiotics may increase resistance and the risk of transmission of resistant strains.

T38

31150-31245

Epistemic_statement

denotes

Conclusions: Resistance to several first-line antibacterials is a continuing problem worldwide.

T39

33055-33150

Epistemic_statement

denotes

The best example of functions associated to a plasmid is given by the antimicrobial resistance.

T40

33732-33919

Epistemic_statement

denotes

Plasmid-mediated antimicrobial resistance arises from a complex multifactorial process supported by a panoply of mobile genetic elements that contain and transfer resistance determinants.

T41

34543-34723

Epistemic_statement

denotes

Among the most important issues of clinical microbiology, increasing prevalence of bacterial pathogens expressing resistance to multiple antimicrobial agents is of special concern.

T42

34724-34896

Epistemic_statement

denotes

The observed high frequency of multiresistance suggests mechanisms by which bacterial species can concentrate and efficiently exchange a variety of resistance determinants.

T43

34897-35048

Epistemic_statement

denotes

Lateral gene transfer, which has been proposed as a fundamental process underlying bacterial diversity, is mainly mediated through plasmids and phages.

T44

35931-36065

Epistemic_statement

denotes

By inserting within a coding sequence they may inactivate the gene, or by inserting upstream of a gene they may modify its expression.

T45

36066-36140

Epistemic_statement

denotes

ISs may also help integration of plasmids into the chromosome of bacteria.

T46

36141-36369

Epistemic_statement

denotes

Some ISs, such as ISEcp1, are capable of mobilising nearby DNA, by a mechanism similar to one-ended-transposition, while others may form a composite transposon, being capable of carrying the sequence located between the two ISs.

T47

36559-36756

Epistemic_statement

denotes

The association of integrons with transferable elements may promote rapid dissemination among clinical strains, and create further opportunities for inclusion of additional resistance determinants.

T48

36757-36967

Epistemic_statement

denotes

Recently novel genetic structures, Repeated Elements (Re), have been described being capable of mobilising resistance genes through a transposition/recombination process that still needs to be fully understood.

T49

36968-37119

Epistemic_statement

denotes

The study of novel resistance mechanisms and their underlying genetic background revealed novel mobile DNA elements responsible for their mobilisation.

T50

37120-37376

Epistemic_statement

denotes

These elements are of interest for clinical microbiology, since they are associated to the emergence of novel antibiotic resistance genes, and for fundamental research, since novel genetic mechanisms for gene mobilisation and dissemination were identified.

T51

38906-39047

Epistemic_statement

denotes

This suggests that IS91 might enhance excision and integration of cassettes that are situated within replication range of IS91-like elements.

T52

39048-39175

Epistemic_statement

denotes

If the two gene capture systems are indeed engaged in a functional crosstalk this could explain their frequent co-localisation.

T53

39389-39459

Epistemic_statement

denotes

The recombinational spread of sul genes is cryptic and may be diverse.

T54

39460-39568

Epistemic_statement

denotes

However, one of the genes, sul1, is strongly linked with both integrons and common regions of the IS91 type.

T55

39569-39805

Epistemic_statement

denotes

Sulfonamides were introduced prior to other modern antibacterial drugs suggesting that it was the key selecting factor for making the dual recombinational platform of integrons and IS91-like elements fixed in most bacterial populations.

T56

39966-40008

Epistemic_statement

denotes

17th ECCMID / 25th ICC, Oral presentations

T57

40009-40226

Epistemic_statement

denotes

Bacteria are noteworthy for their remarkable genetic plasticity responding and adapting to environmental changes that often as not involves the exchanging of DNA molecules in the same cell and between bacterial cells.

T58

40554-40678

Epistemic_statement

denotes

ISCRs were also interesting in that they are intimately associated with different resistance genes carried on each integron.

T59

40679-40952

Epistemic_statement

denotes

ISCR elements have been found in many Gram-negative bacteria and have been associated with an array of different antibiotic resistant functions including qnr, ESBLs, AmpC b-lactamases, metallo-b-lactamases, aminoglycoside and chloramphenicol resistance, dhfr and sul genes.

T60

41286-41362

Epistemic_statement

denotes

These motifs have been shown to be involved in DNA recognition and mobility.

T61

41363-41496

Epistemic_statement

denotes

ISCR elements are very unusual in that, like IS91, they can mobilise large sections of adjacent DNA via a rolling circle replication.

T62

41705-41837

Epistemic_statement

denotes

Many elements are found next to class 1 integrons which we believe to be expressed and active -possibly driven by a hybrid promoter.

T63

42580-42797

Epistemic_statement

denotes

We have previously shown that Extracellular Slime Glycoliprotein (GLP) produced by all mucoid and non mucoid strains is a potent activator of NFkb transcriptional activity and TNF-a induction in fresh human monocytes.

T64

43947-44115

Epistemic_statement

denotes

Challenging of HEK-293 cells expressing only mannose receptor with Slime GLP or viable bacteria resulted in NFkb activation by 6−10 fold and 20−30 fold correspondingly.

T65

44305-44541

Epistemic_statement

denotes

Conclusion: Our results suggest that mannose receptor acts not only as phagocytosis receptor for P. aeruginosa, but also as signaling receptor and cooperates with TLR2 for maximum NFkb activation and proinflammatoty cytokine production.

T66

44626-44714

Epistemic_statement

denotes

Challenges in pharmacokinetics and pharmacodynamics S11 PK/PD in critically ill patients

T67

44715-44857

Epistemic_statement

denotes

Antimicrobial treatment of infections in critically ill patients remains a significant challenge with persisting high mortality and morbidity.

T68

44858-44954

Epistemic_statement

denotes

Early and appropriate antibacterial therapy remains an important intervention for such patients.

T69

44955-45245

Epistemic_statement

denotes

To optimise antibacterial therapy, the clinician should possess not only knowledge of the pharmacokinetic and pharmacodynamic properties of commonly used antimicrobials, but also how these parameters may be affected by the pathophysiological changes occurring during sepsis or septic shock.

T70

45246-45292

Epistemic_statement

denotes

Pathophysiological changes can be contrasting.

T71

45293-45405

Epistemic_statement

denotes

Sepsis, and the nonantibiotic treatment, increasing renal preload may result in higher antibacterial clearances.

T72

45406-45557

Epistemic_statement

denotes

Alternatively, sepsis can induce multiple organ dysfunction, including renal and/or hepatic dysfunction, causing a decrease in antibacterial clearance.

T73

45558-45727

Epistemic_statement

denotes

Aminoglycosides, b-lactams and carbapenems are distributed in plasma and interstitial space, therefore their concentrations could be dramatically affected during sepsis.

T74

45728-45801

Epistemic_statement

denotes

These drugs can have a higher Vd during sepsis leading to a reduced Cmax.

T75

45802-45950

Epistemic_statement

denotes

Some patients with serum creatinine within the normal range can have higher than normal drug clearances, thereby producing low serum concentrations.

T76

45951-46021

Epistemic_statement

denotes

If a drug needs to have a minimum serum concentration maintained (e.g.

T77

46022-46108

Epistemic_statement

denotes

b-lactams), a high drug clearance will lead to underdosage for renally excreted drugs.

T78

46109-46279

Epistemic_statement

denotes

All b-lactams should, in such patients, be administered more frequently than suggested in non-sepsis patients; administration by continuous infusion should be considered.

T79

46280-46496

Epistemic_statement

denotes

In relation to the aminoglycosides, this means that not only are large doses required to be administered, but because of a high CLCR these antibacterials may also need dosing even more frequently than every 24 hours.

T80

46643-46766

Epistemic_statement

denotes

If this were true these antibacterials would also need to have higher daily doses than proposed in the standard literature.

T81

46909-47026

Epistemic_statement

denotes

Data suggest that effective antibacterial therapy remains the most important intervention available to the clinician.

T82

47027-47189

Epistemic_statement

denotes

In treating sepsis, a clinician must be aware of the impact of the various pathophysiological and subsequent pharmacokinetic changes that can occur during sepsis.

T83

47457-47592

Epistemic_statement

denotes

In clinical practice, however, consecutive applications are common but the effect on the bacterial density on hands is largely unknown.

T84

48973-49058

Epistemic_statement

denotes

The difference between the four treatments, however, was not significant (p = 0.089).

T85

49589-49912

Epistemic_statement

denotes

Overall, a simple 1.5 min application of a well-formulated propanolbased hand rub for surgical hand disinfection keeps the bacterial density as low as possible even in two consecutive surgical procedures of 3 h. Conclusions: HPV is more effective than standard terminal cleaning for the eradication of nosocomial pathogens.

T86

50824-50894

Epistemic_statement

denotes

A/C-R was rare (0.4%) and noted in 3 nations; highest (5.5%) in Spain.

T87

53203-53347

Epistemic_statement

denotes

Persistent resistance to NA was associated with an increase in MIC, number of mutations in the gyrA and parC genes and presence of efflux pumps.

T88

53458-53611

Epistemic_statement

denotes

The carriage of E. coli NAR was not associated with the child's age or gender, use of antibiotics, or carriage of E. coli NAR among mothers and siblings.

T89

53612-53881

Epistemic_statement

denotes

Conclusions: The lack of evidence for intra-familiar spread of E. coli NAR and the significant acquisition of E. coli NAR in 2 specific DCCs suggest that other means of transmission such as the food or waterborne routs may explain the high carriage rate of E. coli NAR.

T90

53882-54042

Epistemic_statement

denotes

Persistent carriage of E. coli NAR is of concern in view of the association with an increase in both phenotypic and genetic markers of resistance to quinolones.

T91

54043-54109

Epistemic_statement

denotes

rarely cultured enterococci had a MIC90 of 2 mg/L (range, 2 mg/L).

T92

55912-56050

Epistemic_statement

denotes

This has been accomplished by enforcing preventive contact isolation of all hospitalised patients suspected or confirmed as MRSA positive.

T93

56051-56261

Epistemic_statement

denotes

This has been facilitated by the fact that in these countries the predominant risk factor for patients for MRSA acquisition was hospitalisation abroad, making these at-risk patients relatively easy to identify.

T94

57218-57319

Epistemic_statement

denotes

This could indicate that there is a continued influx of MRSA from high prevalence areas into Denmark.

T95

57320-57546

Epistemic_statement

denotes

Strains belonging to the ST80-IV complex have been the most frequent cause of CA-MRSA in Denmark, however, an increasing diversification has recently been observed including almost all strains known as associated with CA-MRSA.

T96

57633-57727

Epistemic_statement

denotes

This has happened despite continued use of contact isolation of MRSA positive patients during.

T97

57728-57917

Epistemic_statement

denotes

Hospitalisation of MRSA carriers not identified on admission due to lack of risk factors is probably one important factor responsible for the increased number of nosocomial MRSA in Denmark.

T98

57918-58177

Epistemic_statement

denotes

An increase in the prevalence of MRSA outside hospitals including in otherwise healthy persons, is thus of great concern as this not only gives rise to CA-MRSA infections but also inevitably will increase the risk of nosocomial MRSA infec-tions and outbreaks.

T99

58178-58362

Epistemic_statement

denotes

In order to keep Denmark as a low prevalence country we believe that MRSA should be contained and eradicated not only in hospitalised patients but also when diagnosed in the community.

T100

58521-58638

Epistemic_statement

denotes

The first question to ask when considering any screening programme for the identification of CA-MRSA carriage is why?

T101

58639-58703

Epistemic_statement

denotes

The importance of epidemiological data cannot be underestimated.

T102

58704-58814

Epistemic_statement

denotes

Data on prevalence can inform empirical therapy requirements or help in the design of intervention strategies.

T103

58815-58993

Epistemic_statement

denotes

Prevalence can be established for the population in general, or, specific subgroups such as children, military personnel, indigenous or disadvantaged populations can be targeted.

T104

58994-59127

Epistemic_statement

denotes

Community intervention measures similar to the 'search and destroy' techniques used in hospitals would require large-scale screening.

T105

59128-59303

Epistemic_statement

denotes

A narrower approach concentrating on high-risk groups to enable programmes such as education on hygiene to reduce transmission would allow a more targeted screening programme.

T106

59972-60064

Epistemic_statement

denotes

The value of screening healthcare workers for carriage of CA-MRSA has yet to be established.

T107

60065-60100

Epistemic_statement

denotes

How to screen is the next question.

T108

60136-60175

Epistemic_statement

denotes

Which laboratory method should be used?

T109

60176-60348

Epistemic_statement

denotes

The ideal test would have high negative and positive predictive values, be rapid, inexpensive, applicable to the routine laboratory, and have high through put capabilities.

T110

60950-60997

Epistemic_statement

denotes

The last questions are when and whom to screen.

T111

61065-61214

Epistemic_statement

denotes

The range can be from large-scale periodic population screening for epidemiological purposes to continual hospital unit, high-risk patient screening.

T112

61215-61296

Epistemic_statement

denotes

There are no established guidelines or recommendations for screening for CA-MRSA.

T113

61297-61411

Epistemic_statement

denotes

Many questions have yet to be answered particularly, whether control of transmission in the community is possible.

T114

61412-61534

Epistemic_statement

denotes

By looking at what evidence is available we can move a step closer to control of this very significant community pathogen.

T115

61914-62181

Epistemic_statement

denotes

Given that CA-MRSA has been now been implicated in healthcare-associated infections, efforts to reduce the spread of this organism within the healthcare environment are also important and include appropriate hand-hygiene, isolation, and environmental decontamination.

T116

62182-62269

Epistemic_statement

denotes

Incision and debridement remains critical in the management of most CA-MRSA infections.

T117

62270-62494

Epistemic_statement

denotes

The use of antibiotics is indicated in many CA-MRSA infections and therapeutic options include older agents, such as clindamycin, trimethoprimsulfamethoxazole, tetracyclines, and rifampin, and newer agents such as linezolid.

T118

63624-63846

Epistemic_statement

denotes

The range of receptors involved in the innate response to pneumococci in the respiratory tract is starting to be appreciated and includes Tolllike receptors and receptors primarily involved in the phagocytosis of bacteria.

T119

63847-64043

Epistemic_statement

denotes

The interaction between soluble factors and the resident phagocytes of the lung is being clarified and the complexity of cytokine networks involved in the innate host response is being elucidated.

T120

64173-64436

Epistemic_statement

denotes

Furthermore our understanding of the regulation of the inflammatory response and of the significant role of apoptosis in the regulation of the inflammatory response has lead to important insights into how cell survival and outcome of infection are closely linked.

T121

64437-64644

Epistemic_statement

denotes

These observations are enabling a more scientific interpretation of many of the central clinical features of pneumococcal pneumonia and may encourage novel approaches to therapy to improve disease responses.

T122

65029-65166

Epistemic_statement

denotes

The carrier state is more frequent in young children and may reach over 70% in some populations such as those attending day-care centres.

T123

65475-65641

Epistemic_statement

denotes

In recent years, there has been some debate on the relative contribution of serotype and genetic background to the invasive disease potential of pneumococcal strains.

T124

65642-65695

Epistemic_statement

denotes

We will present a study that addresses this question.

T125

66080-66153

Epistemic_statement

denotes

The invasive disease potential of serotypes and clones will be discussed.

T126

66154-66342

Epistemic_statement

denotes

Pneumococci cause a spectrum of diseases in humans, from reasonably mild diseases like sinusitis and conjunctivitis to potentially lifethreatening diseases like meningitis and bacteraemia.

T127

66515-66690

Epistemic_statement

denotes

Understanding invasive disease epidemiology, both preceding vaccine implementation and after vaccine introduction, is crucial to the design and development of future vaccines.

T128

66691-66902

Epistemic_statement

denotes

Several recent studies have shown that pneumococcal serotypes differ in their invasive disease potential, and this has particular relevance for the selection of serotypes to include in future conjugate vaccines.

T129

66903-67125

Epistemic_statement

denotes

It is also essential to understand the serotype-specific changes that have occurred subsequent to conjugate vaccine implementation in the USA, as a model for what might occur post-vaccine implementation in other countries.

T130

67966-68009

Epistemic_statement

denotes

Each of these presents specific challenges.

T131

68010-68220

Epistemic_statement

denotes

The vaccine has been shown to prevent between 25% and 37% of all cause X-ray confirmed pneumonias and this implies a level of protection against pneumococcal pneumonia due to vaccine serotypes in excess of 70%.

T132

68346-68496

Epistemic_statement

denotes

The major preventable burden of disease in Africa may be among HIV infected children where the vaccine has also been shown to reduce pneumonia burden.

T133

68497-68770

Epistemic_statement

denotes

An innovative aspect of the vaccine is the fact that it may reduce the pneumococcal super infections that follow viral respiratory infections, such as influenza, and conjugate vaccination of children may thus be a useful adjunct to pandemic influenza planning preparedness.

T134

68771-68999

Epistemic_statement

denotes

The interruption of carriage of vaccine serotypes has been shown to reduce IPD in adults in the USA due to herd immunity so the population benefit in an influenza pandemic may extend beyond protection just of immunised children.

T135

69000-69090

Epistemic_statement

denotes

Herd immunity has also recently been shown to protect young un-immunised infants from IPD.

T136

69091-69549

Epistemic_statement

denotes

Conjugate vaccine has had little impact on all cause otitis media in randomised trials, but post-marketing studies in the USA suggest that healthcare utilisation for otitis episodes has reduced significantly post vaccine introduction suggesting a major role for herd immunity and allowing physicians to feel more comfortable in a "wait and see" attitude to otitis once the prospects of significant complications due to the pneumococcus are likely to be rare.

T137

70143-70369

Epistemic_statement

denotes

The implementation of immunisation programmes including conjugate pneumococcal vaccine to infants in European countries affords the opportunity to monitor the impact on all of these health outcomes in both children and adults.

T138

71686-71803

Epistemic_statement

denotes

As the epidemiology of staphylococcal infections changes new therapeutic agents are becoming available to clinicians.

T139

73272-73366

Epistemic_statement

denotes

The recommended dosing regimen is an initial dose of 100 mg, followed by 50 mg every 12 hours.

T140

74239-74374

Epistemic_statement

denotes

They usually occur within the first two days of therapy, are more common in women (48%) than in men (24%), and may also be age related.

T141

74446-74622

Epistemic_statement

denotes

It has a broad spectrum of activity and its ability to evade numerous mechanisms of resistance makes it a promising solution to the treatment of multi-drug resistant organisms.

T142

74677-74841

Epistemic_statement

denotes

The increasing resistance of Gram-negative bacteria and particularly amongst Pseudomonas aeruginosa and Acinetobacter baumannii, raises a major therapeutic problem.

T143

75320-75514

Epistemic_statement

denotes

Because this drug was developed during the 1950s, only little pharmacokinetic and pharmacodynamic information are available and the optimal daily dose for severely ill patients is still unknown.

T144

75813-76034

Epistemic_statement

denotes

Clinical reports on the efficacy of intravenous colistin in these patients are not randomised studies and in most of them, colistin was frequently associated with other antimicrobial agents with a lack of a control group.

T145

76364-76486

Epistemic_statement

denotes

However recent studies demonstrated a reduced toxicity as compared with previous studies, even if a higher dosage is used.

T146

76618-76746

Epistemic_statement

denotes

There are also recent clinical reports on the use of colistin in continuous intravenous infusion to minimise potential toxicity.

T147

76747-76907

Epistemic_statement

denotes

This reduction of toxicity without impairment of efficacy (concentration-dependent killing in in-vitro timekill studies) should be confirmed by further studies.

T148

77077-77237

Epistemic_statement

denotes

This highlights the urgent need to preserve this molecule by the best appropriate dose regimen and by an optimal synergistic combination with other antibiotics.

T149

77560-77773

Epistemic_statement

denotes

The emergence of infections caused by bacteria resistant to almost all antimicrobial agents may have renewed the interest for addressing the contributions, limitations and future clinical indications of this drug.

T150

78454-78684

Epistemic_statement

denotes

The disodium salt of fosfomycin can be administered intravenously in high doses due to its very low toxicity, achieving plasmatic peak levels that are several times above the MIC of susceptible microorganisms (breakpoint 64 g/mL).

T151

79035-79186

Epistemic_statement

denotes

As a counterbalance, fosfomycin can act synergistically with other antibiotics, especially with those that inhibit later points in cell-wall synthesis.

T152

79187-79336

Epistemic_statement

denotes

Such synergism has been shown repeatedly against different strains of Staphylcoccus aureus, CNS, Streptococcus pneumoniae and Pseudomonas aeruginosa.

T153

79614-79775

Epistemic_statement

denotes

However, the reported clinical experience with these combinations is very scarce and, therefore, there are not evidence-based recommendations supporting its use.

T154

79776-80062

Epistemic_statement

denotes

On the other hand, various clinical trials have indicated that fosfomycin trometamol, as a sole antibiotic, is effective and safe for the treatment of uncomplicated UTI, providing high and long lasting urinary fosfomycin levels, which help to prevent the emergence of resistant strains.

T155

80205-80318

Epistemic_statement

denotes

of fosfomycin trometamol may be considered nowadays as a first line therapy for uncomplicated UTI in young women.

T156

80319-80452

Epistemic_statement

denotes

However, the possible emergence of fosfomycin-resistant mutants among ESBL-producing enterobacteriaceae should be taken into account.

T157

80612-80838

Epistemic_statement

denotes

Combinations of iv fosfomycin with other antibiotics may be considered in selected cases, but whether these combinations yield improved outcomes in specific infections due to multirresistant pathogens remains to be determined.

T158

80839-80993

Epistemic_statement

denotes

Logistic reasons and financial limitations will make difficult the realisation of appropriate prospective studies to answer this issue in the near future.

T159

81360-81780

Epistemic_statement

denotes

Chloramphenicol's loss of favour began in the 1960s, when it was shown to have two distinct toxic effects on hematopoiesis: a frequently observed, dose-dependent anaemia, reversible on cessation of therapy, and an irreversible, 'idiosyncratic' aplastic anaemia, which had an incidence of approximately 1 case per 30,000 courses of therapy, a high case fatality rate, and no correlation with the or duration of treatment.

T160

81945-82081

Epistemic_statement

denotes

Analogues of chloramphenicol have been developed that lack the aromatic NO 2 group that is thought to cause irreversible marrow aplasia.

T161

82082-82255

Epistemic_statement

denotes

Although the clinical efficacy of such compounds has not been evaluated, they are effective in vitro against most bacteria, even those that are resistant to chloramphenicol.

T162

82256-82414

Epistemic_statement

denotes

The data provided in support of a hypothesis that these molecules needed a nitro group in order to cause the blood dyscrasias were insufficient in themselves.

T163

82480-82669

Epistemic_statement

denotes

The potential for florfenicol to cause blood dyscrasias, such as aplastic anaemia, in humans was discussed in relation to the chemically related chemicals chloramphenicol and thiamphenicol.

T164

82670-82809

Epistemic_statement

denotes

Human epidemiological data could not be used to demonstrate the safety of florfenicol as florfenicol has never been used in human medicine.

T165

82810-83085

Epistemic_statement

denotes

Nevertheless, because there is as yet no way to monitor the potential for irreversible bone marrow toxicity, it is unlikely that such compounds will become available for the treatment of chloramphenicolresistant infections in general -and meningococcal disease in particular.

T166

83317-83501

Epistemic_statement

denotes

It would, however, be a very good thing if we could find a new drug or group of drugs that produced similar results in fighting infection but did not have as many serious side effects.

T167

83502-83632

Epistemic_statement

denotes

It would take a long time before any drug could ever replace chloramphenicol, because of both its broad use and its very low cost.

T168

83633-83768

Epistemic_statement

denotes

Tropical medicine: from basic science to field work O57 Evaluation of malaria status and immune response to Plasmodium falciparum MSP-2

T169

83769-83947

Epistemic_statement

denotes

Objectives of study: MSP-2 is a highly polymorphic 45−53 kDa merozoite surface antigen and very immunogenic malaria antigen, which is considered as a promising vaccine candidate.

T170

84054-84162

Epistemic_statement

denotes

Many studies have suggested a protective role for specific IgG antibodies against variable regions of MSP-2.

T171

84341-84512

Epistemic_statement

denotes

The association of haemoglobin and parasitaemia as two indicators of clinical malaria with acquired immunity were analysed to elucidate the pattern of protective immunity.

T172

85217-85490

Epistemic_statement

denotes

Increasing the age was negatively correlated with parasitaemia and positively with IgG antibody responses and haemoglobin levels indicating that total IgG responses to domains 2, 3 and crude schizont extract coincidental to a decrease in parasitaemia density and frequency.

T173

85761-86064

Epistemic_statement

denotes

Conclusion: IgG3 was the main antibody, mainly against domain 3 of MSP-2, that was associated with increase in haemoglobin levels and decrease in parasitaemia suggesting that domain 3 is preferred over other domains and crude schizont extract in presenting a clearer picture of immunity against malaria.

T174

86065-86246

Epistemic_statement

denotes

These results could be an evidence of protective role of these antibodies against malaria disease and, therefore, domains 3 can be considered as reliable vaccine candidate antigens.

T175

86315-86416

Epistemic_statement

denotes

Serosurveillance indicates that almost all native adults have been infected, mostly asymptomatically.

T176

86523-86711

Epistemic_statement

denotes

Even though some of its peer flaviviruses are known to reside persistently within the host and contribute to host illnesses, dengue virus has not been shown to behave in a similar fashion.

T177

87542-87684

Epistemic_statement

denotes

Demographic data of all patients were analysed, especially for the history of recent febrile illnesses which could be due to dengue infection.

T178

87685-87813

Epistemic_statement

denotes

Background: Intermittent preventive antimalarial treatment of infants (IPTi) is considered a promising malaria control strategy.

T179

87986-88055

Epistemic_statement

denotes

Studies modeling the effect of malaria incidences on IPTi are scarce.

T180

88056-88180

Epistemic_statement

denotes

The aim of this study was to describe how far protective efficacy of IPTi depends on the incidence rate of clinical malaria.

T181

89111-89323

Epistemic_statement

denotes

Interpretation : Correlations between IPTi efficacy and malaria incidences may have implications on IPTi implementation strategies I will discuss the role mathematical modelling in pandemic planning and response.

T182

89324-89498

Epistemic_statement

denotes

Recent research examining whether antiviral prophylaxis and social distance measures could be used to contain a nascent pandemic at its point of origin will then be reviewed.

T183

89499-89659

Epistemic_statement

denotes

Containment is potentially feasible, but requires rapid detection of the initial transmissible case cluster and a rapid and organised response to each new case.

T184

89660-89712

Epistemic_statement

denotes

These may be demanding criteria for much of SE Asia.

T185

89713-89872

Epistemic_statement

denotes

If containment fails, slowing spread becomes a policy priority and in that context I will discuss the potential impact of restrictions on international travel.

T186

90655-90880

Epistemic_statement

denotes

Apart from neutropaenic enterocolitis, a broad spectrum of infections associated with impairment of mucosal barriers may be clinically important, e.g., streptococcal bacteraemia, septic enterococcal infection, or candidaemia.

T187

91092-91212

Epistemic_statement

denotes

Primary removal of foreign material may be important for the successful management of these catheter-related infections.

T188

91213-91542

Epistemic_statement

denotes

Allogeneic hematopoietic stem cell transplantation with reducedintensity conditioning has become more common also for treatment of aggressive haematologic malignancies in elderly patients as well as in patients with severe co-morbidity, who formerly have not been taken into consideration for myeloablative transplant procedures.

T189

91543-91821

Epistemic_statement

denotes

Despite a marked reduction of complications related to pancytopenia combined with acute graft-versus-host reaction, the rate of severe and life-threatening fungal infections and cytomegalovirus diseases has turned out to be comparable to conventional allogeneic transplantation.

T190

91995-92353

Epistemic_statement

denotes

Tuberculosis: fast forward to new approaches S17 The broad introduction of monoclonal antibodies to CD20 and CD52 and of nucleoside analogs into the treatment of patients with B-or T-cell lymphomas has lead to long-term depletion of B cells, eventually associated with decreasing levels of serum immunoglobulins, and T-cell deficiency lasting for many years.

T191

92577-92759

Epistemic_statement

denotes

Targeted prophylaxis is warranted for selected patient groups, whereas high alertness and early pre-emptive antimicrobial intervention is mandatory in the majority of these patients.

T192

93146-93271

Epistemic_statement

denotes

However, this method is technically demanding and labour intensive, and requires weeks of culturing to obtain sufficient DNA.

T193

93272-93338

Epistemic_statement

denotes

The complex RFLP patterns are difficult to interpret and exchange.

T194

94386-94515

Epistemic_statement

denotes

The use of 15 selected loci is recommended as the new international gold standard for typing of M. tuberculosis complex isolates.

T195

94516-94628

Epistemic_statement

denotes

A recent study pointed out that VNTR typing on basis of 24 loci is useful to study the phylogeny of the complex.

T196

94629-94756

Epistemic_statement

denotes

As experienced after the standardisation of IS6110 RFLP typing in 1993, it is expected that the recent (December 2006; J. Clin.

T197

95259-95500

Epistemic_statement

denotes

Because in the epidemiology of tuberculosis transmission and manifestation of the disease can be separated in time by multiple years, the switch to VNTR typing can not be done without any overlap of the application of the two typing methods.

T198

95941-96037

Epistemic_statement

denotes

During these 6 months, such a case of TB is likely to infect, on the average, 10 close contacts.

T199

96038-96174

Epistemic_statement

denotes

If one of these 10 newly infected contacts then develops TB sometime in his life time, he will infect 10 other persons before diagnosis.

T200

96206-96321

Epistemic_statement

denotes

Thus, if a TB control programme is only focused on the treatment of active cases, TB will never come under control.

T201

96322-96520

Epistemic_statement

denotes

The fundamental question in TB control, therefore, is "can we predict who among the latently infected people will progress to active disease so that such a person can be given preventive treatment?"

T202

96521-96626

Epistemic_statement

denotes

To answer this question, the mechanism of Mtb persistence and reactivation needs to be better understood.

T203

96627-96700

Epistemic_statement

denotes

A variety of models for bacterial persistence has been proposed recently.

T204

96701-96901

Epistemic_statement

denotes

Most genetic studies that provide evidence for the putative role of a gene in persistence are based on demonstrating that an Mtb strain disrupted in such a gene is attenuated in an animal model of TB.

T205

96902-97027

Epistemic_statement

denotes

However, several recent gene disruption studies have shown that Mtb mutants can also become hypervirulent in an animal model.

T206

97028-97206

Epistemic_statement

denotes

This suggests that some Mtb genes may actually help to temper the virulence potential of Mtb so that the organism can establish a stable niche in a host without harming the host.

T207

97380-97610

Epistemic_statement

denotes

The operon appears to respond to a signal induced by the host's granuloma cell turnover, while the host's proinflammatory cells that comprise the granulomas appear to respond to the changing bacterial cell envelope lipid turnover.

T208

98029-98152

Epistemic_statement

denotes

This mutant is also hypervirulent but for an opposite reason-it causes rapidly progressive, hyper-proinflammatory response.

T209

98153-98342

Epistemic_statement

denotes

Thus, the mce1 operon appears to serve as a homeostatic regulator of pro-inflammatory response by the host, helping to establish a balanced relationship favourable to both the host and Mtb.

T210

98343-98614

Epistemic_statement

denotes

Understanding and exploiting this relationship may lead to new ways to predict a subset of latently infected people who progresses to active disease; it may also lead to the development of a therapeutic vaccine to prevent latently infected people from ever developing TB.

T211

99496-99679

Epistemic_statement

denotes

Objectives: Staphylococcus aureus can be a respiratory pathogen in cystic fibrosis (CF) and its pathogenicity is related to a combination of virulence and antibiotic-resistance genes.

T212

99680-99731

Epistemic_statement

denotes

Little is known about the agr-group in CF-isolates.

T213

100889-101257

Epistemic_statement

denotes

agrI was associated with the presence of many virulence-genes such as cytotoxins and proteases (sea-lukE-splB) and in one agrI isolate lukS/F-PVL was found; agrII also possessed an adhesin sdrE; agrIII was associated with adhesins and enterotoxin (fnbA-sea-cna), the exfoliatinA was never detected; agrIV possessed the cytotoxin lukE, adhesin cna and exfoliatinA, eta.

T214

101258-101394

Epistemic_statement

denotes

Protease gene (splB) was always found associated with cytotoxin lukE in agrI-II-III and, mostly, sdrE adhesin was associated with these.

T215

101395-101550

Epistemic_statement

denotes

A frequent inversecorrelation was found between cna and lukE-splB in all agr-groups and a close correlation was observed between cap8 and cna in agrIII-IV.

T216

101551-101945

Epistemic_statement

denotes

Conclusion: Our data demonstrated for the first time an increase of MRSA in our centre; furthermore, CF-persistent infections were not associated with a distinct agr-specificity group or a diffused antibioticresistance of the strains, but rather S. aureus isolates have a complex distribution and combination of virulence determinants which contribute to S. aureus pathogenicity in CF patients.

T217

103034-103184

Epistemic_statement

denotes

The increased proliferation of neural progenitors suggests that endogenous mechanisms may limit consequences of neuronal destruction after meningitis.

T218

103185-103287

Epistemic_statement

denotes

Stimulation of neurogenesis might help to improve therapy of acute inflammatory diseases of the brain.

T219

104393-104495

Epistemic_statement

denotes

Calorimetric detection of microbial growth may be more sensitive and rapid than blood culture systems.

T220

107432-107571

Epistemic_statement

denotes

The comparison of patient samples correlated with this by showing an increase of 59% in the rate of detection of MRSA following enrichment.

T221

107572-107858

Epistemic_statement

denotes

In conclusion enrichment has proven to dramatically increase the sensitivity and rate of detection of MRSA compared to direct culture alone and in order to ensure maximum sensitivity in the detection of MRSA enrichment should be employed as the method of choice in routine laboratories.

T222

107860-108167

Epistemic_statement

denotes

The limited additional help of the inflammatory markers CRP or PCT in bacteraemia prediction compared to a model of clinical assessment and routine laboratory information required for septic evaluation suggest the need for further justification of the use of these measurements in cost-constrained settings.

T223

108548-108717

Epistemic_statement

denotes

In addition, within the last two years an increasing number of community-acquired (CA)-MRSA could also be noted in the Netherlands, which represent an additional danger.

T224

109457-109639

Epistemic_statement

denotes

However, the majority of spa types on the German side were in concordance to the national epidemiological trend with spa t001, t002, t003, t004 and t032 as the most common spa types.

T225

109640-109838

Epistemic_statement

denotes

The spa type t044 -often associated with CA-MRSA in central Europe -was detected on both sides; 1% on the German and~15% on the Dutch side of the border, underlining the emerging problem of CA-MRSA.

T226

110093-110148

Epistemic_statement

denotes

However, cross-border spread of MRSA was also detected.

T227

110274-110379

Epistemic_statement

denotes

Objectives: The success of pandemic hospital-acquired MRSA clones may be due to high adhesive properties.

T228

110545-110689

Epistemic_statement

denotes

agr dysfunction is associated with overexpression of certain adhesins and seems to be responsible of the success of the CMRSA-3 clone in Canada.

T229

111302-111433

Epistemic_statement

denotes

The adhesin gene profile (bbp, can, eno, ebpS, fib, clfA, clfB, fnbA and fnbB) was determined with multiplex PCR for each isolates.

T230

112124-112263

Epistemic_statement

denotes

No correlation between the adhesive property and the absence of deltahaemolysin production was observed, both in MRSA and in MSSA isolates.

T231

112264-112462

Epistemic_statement

denotes

We demonstrated that adhesive properties onto HAECs of MRSA Lyon clone isolates was higher than that MSSA isolates, but was heterogeneous despite similar genetic background and adhesin gene profile.

T232

112463-112554

Epistemic_statement

denotes

This could be the result of overexpression of adhesins independently of an agr dysfunction.

T233

112726-112973

Epistemic_statement

denotes

The ST8-SCCmec IVa (or socalled USA-300) clone has been associated with community outbreaks, nosocomial transmission, and identified as the primary cause of skin and soft tissue infections (SSTI) presenting to Emergency Departments across the USA.

T234

114679-114803

Epistemic_statement

denotes

Whilst numbers remain small, the occurrence of community-based clusters and the death of one patient give cause for concern.

T235

117978-118077

Epistemic_statement

denotes

With cipro, 7 subjects were clinical successes, 2 were failures and for 3, the outcome was unknown.

T236

118078-118238

Epistemic_statement

denotes

The urine pathogen was eradicated in 10 and was unknown for 1 levo subject compared to eradicated in 7, persisted in 3, and unknown in 2 cipro-treated subjects.

T237

118466-118521

Epistemic_statement

denotes

The outcome for the cipro-resitant E. coli was unknown.

T238

119577-119763

Epistemic_statement

denotes

MRSA infections appeared to be more common in patients who were younger, of Black racial origin, and in those with a major abscess compared with patients with infections not due to MRSA.

T239

119879-119959

Epistemic_statement

denotes

Yet, the prevalence of microbial resistance to aminoglycosides has remained low.

T240

120561-120743

Epistemic_statement

denotes

We conclude that each of the three major clones can readily be demarcated from other A. baumannii members, and that molecular diagnostics could be developed to identify them rapidly.

T241

120744-121034

Epistemic_statement

denotes

Analysis of the recombination/mutation rate shows that nucleotides do not change by recombination more frequently than by mutation, showing that recombination is unlikely to disrupt the clonal frame of the clones, which can therefore be expected to be stable over very long periods of time.

T242

121205-121318

Epistemic_statement

denotes

Therefore, there is a critical need to understand the correspondence between types produced by different methods.

T243

121319-121537

Epistemic_statement

denotes

This may be useful not only for the comparison of the genetic backgrounds of the particular set of isolates under study but also to produce a broader view of how the results of the different typing methods are related.

T244

121827-121969

Epistemic_statement

denotes

2006) and is now implemented in a free-access web-based interface, on which users can analyse their data anonymously and retrieve the results.

T245

122702-122844

Epistemic_statement

denotes

Based on these measures the users can quantitatively evaluate the discriminatory power of the typing methodologies used and their concordance.

T246

123008-123189

Epistemic_statement

denotes

This can be used to evaluate the predictive power of a typing methodology when compared to another, which can guide the user in the choice of a 'gold standard' for clone definition.

T247

123190-123354

Epistemic_statement

denotes

Furthermore, as new microbial typing methods are proposed, this methodology allows for their comparison in terms of type assignments with established methodologies.

T248

123355-123551

Epistemic_statement

denotes

Despite several case control studies and enhanced surveillance of both human cases and animal environmental isolates, there is still much unknown about the epidemiology of Campylobacter infection.

T249

124069-124209

Epistemic_statement

denotes

We describe here an analysis of the three year study data and steps taken to adapt the methodology for use in routine surveillance settings.

T250

124210-124418

Epistemic_statement

denotes

The study has demonstrated several interesting correlations between specific sequence types and a number of explanatory variables for disease (eg month of infection, locality of residence, and travel abroad).

T251

124419-124579

Epistemic_statement

denotes

Other studies provide increasing evidence of host-association for specific MLST types of campylobacter and these findings are related to the three year dataset.

T252

124580-124778

Epistemic_statement

denotes

In addition, many new types have been described in surface waters from this project and there is evidence for a distinct water-borne population that has not so far been described in human infection.

T253

125154-125230

Epistemic_statement

denotes

-In some place typical rickettsioses could be caused by different organisms.

T254

125231-125360

Epistemic_statement

denotes

In such cases, the new Rickettsia was misdiagnosed with a previously identified bacterium (such as R. massiliae with R. conorii).

T255

125508-125633

Epistemic_statement

denotes

These findings challenge the old dogma postulating that of one tick borne rickettsiosis was prevalent in one geographic area.

T256

125842-126006

Epistemic_statement

denotes

R. felis, a flea-transmitted spotted fever, and R. parkeri, a tick-transmitted spotted fever, have been shown since to infect human beings in the USA and in Urugay.

T257

126071-126163

Epistemic_statement

denotes

Many Rickettsia have been identified in ticks but have not been currently found in patients.

T258

126164-126223

Epistemic_statement

denotes

These Rickettsiae should be considered potential pathogens.

T259

126224-126312

Epistemic_statement

denotes

These new findings should stimulate investigations to identify new rickettsial diseases.

T260

126313-126390

Epistemic_statement

denotes

Patients with atypical rash or fever after arthropod bite should be targeted.

T261

126504-126612

Epistemic_statement

denotes

Can pharmacokinetic-pharmacodynamic parameters drive dosing regimens that are less vulnerable to resistance?

T262

126727-126730

Epistemic_statement

denotes

Pro

T263

126731-127012

Epistemic_statement

denotes

In recent years, the rules for selection of antimicrobial agents have been undergoing critical revision in terms of optimum dosing for control of infectious diseases, with the goal of potentiating treatment efficacy and reducing the risk of selecting multidrug resistant pathogens.

T264

127013-127295

Epistemic_statement

denotes

The most important criterion for rational choice of an antimicrobial agent is defined by its pharmacodynamic (PD) characteristics, and thus its antimicrobial activity which can be summarised as the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC).

T265

127296-127676

Epistemic_statement

denotes

The second criterion for selecting an antibiotic is due to its pharmacokinetic (PK) characteristics, since it has been demonstrated that antibiotic concentrations at the infection site influence the intensity and duration of the effect, and together with the PD parameters, provide a general inter-relationship and contribute to defining the potential clinical efficacy of a drug.

T266

127866-128028

Epistemic_statement

denotes

Moreover, the principles that link concentrations of antibiotics in humans and their effects have been outlined in order to determine the optimal dosing interval.

T267

128095-128234

Epistemic_statement

denotes

the newer quinolones and aminoglycosides, should be administered as a single daily dose to maximise the peak serum concentration/MIC ratio.

T268

128304-128586

Epistemic_statement

denotes

Existing data on fluoroquinolones suggest that a ratio of 100-125 correlates with high bacterial eradication and optimal clinical outcome in infections due to Gram-negative pathogens, while a ratio of 50 is associated with a high probability of eradication of S. pneumoniae strains.

T269

128587-128870

Epistemic_statement

denotes

For this group of antibiotics the new concept of the so called mutant prevention concentration (MPC) and mutant selection window (MSW) may be helpful in restricting the enrichment of mutant subpopulations and consequently, at least partially, in controlling the spread of resistance.

T270

128871-129107

Epistemic_statement

denotes

Beta-lactams, having time-dependent efficacy, usually do not have great post antibiotic effects (PAEs), and the parameter which seems to better correlate PD with PK is the time duration with concentrations higher than the MIC (T > MIC).

T271

129278-129723

Epistemic_statement

denotes

In summary, we can theoretically optimise the dosage regimen of antibiotics (dose, administration route and interval between doses) in clinical practice by correlating the PK and PD pertaining to each antibiotic class, based on experimental animal studies and these PK/PD parameters may contribute to the containment of resistance for all drug classes and especially the most important ones used in serious infections in intensive care patients.

T272

130491-130774

Epistemic_statement

denotes

In low-resource countries, effective surveillance programmes are difficult to implement for a number of reasons, including scarce financial resources, lack of laboratory facilities and, where laboratories do exist, lack of quality control, reliable reagents and adequate supervision.

T273

130775-130919

Epistemic_statement

denotes

In these settings, the development of reliable and low-cost alternative methods could facilitate the implementation of large-scale surveillance.

T274

131080-131398

Epistemic_statement

denotes

This bacterial population, although not being a specific target, is continuously exposed to the selective pressure generated by antimicrobial chemotherapy and may become a potential reservoir of resistant strains that can cause infections, and of resistance determinants that can be transferred to pathogenic bacteria.

T275

131399-131641

Epistemic_statement

denotes

Therefore, surveillance of antibiotic-resistant bacteria carried by healthy individuals is considered an indicator of the spread of antibiotic resistance that could also be useful to predict the emergence of resistance in pathogenic bacteria.

T276

131642-131821

Epistemic_statement

denotes

In this perspective, resistance patterns of some members of the commensal microbiota, such as the faecal Escherichia coli, have been evaluated in various epidemiological settings.

T277

132513-132669

Epistemic_statement

denotes

Many susceptibility testing methods recommended the use of ESBL screening and confirmation tests on a routine basis, including CLSI, BSAC, CA-SFM, and SRGA.

T278

132670-132743

Epistemic_statement

denotes

However, a number of issues have emerged with routine use over the years:

T279

132744-132746

Epistemic_statement

denotes

1.

T280

132747-132847

Epistemic_statement

denotes

The problem of defining an adequate number of substrates to ensure sufficiently sensitive screening.

T281

132848-133054

Epistemic_statement

denotes

Ideally, one should include a minimum of 4, namely cefpodoxime, ceftazidime, ceftriaxone or cefotaxime, and aztreonam, and at concentrations that often differ from those used for susceptibility breakpoints.

T282

133159-133343

Epistemic_statement

denotes

Some of these species have been shown to be important reservoirs for ESBLs, and resistance to extended-spectrum cephalosporins cannot solely attributed to stable de-repression of AmpC.

T283

133600-133756

Epistemic_statement

denotes

Such strains have been shown to harbour OXA enzymes, inhibitor-resistant TEM enzymes, or particularly plasmid-borne AmpC enzymes with significant frequency.

T284

133757-133967

Epistemic_statement

denotes

Thus there is no current phenotypic or genotypic test that can be practically and effectively applied in the routine laboratory with sufficient sensitivity to detect the emerging range of transmissible enzymes.

T285

133968-134079

Epistemic_statement

denotes

However, we can rely to a great extent on the selection of or change to appropriate susceptibility breakpoints.

T286

134080-134269

Epistemic_statement

denotes

A range of recent studies has suggested that failures of treatment with extendedspectrum cephalosporins are likely when strains of Enterobacteriaceae have MICs elevated above the wild-type.

T287

134270-134579

Epistemic_statement

denotes

Further, application of pharmacokinetic/pharmacodynamic (PK/PD) principles to the most widely recommended dosing schedules of cephalosporins suggest that the susceptibility breakpoints recommended by many methods are too high, and should to lowered to values that fortunately coincide wild-type cutoff values.

T288

134580-134919

Epistemic_statement

denotes

Hence, lowering of susceptibility breakpoints for extendedspectrum cephalosporins to those defined by PK/PD will indicate the presence of an ESBL or plasmid-borne AmpC enzyme with sufficiently high likelihood to allow laboratories to report both resistance to these agents and provide advice about appropriate infection control procedures.

T289

134920-135120

Epistemic_statement

denotes

Objectives: Since antibiotic resistance often is associated with a biological fitness cost for bacteria it is assumed that a reduction of antibiotic use is followed by a reduction in resistance rates.

T290

135323-135541

Epistemic_statement

denotes

So far no prospective intervention in the community has been carried out to investigate whether a substantial decrease of the use of a single antibiotic will result in a corresponding decrease in antibiotic resistance.

T291

136673-136802

Epistemic_statement

denotes

Resistance to NIT and MEC did not increase despite the substantial increase in the use of these drugs, 31% and 69%, respectively.

T292

137207-137304

Epistemic_statement

denotes

Whether the increase in FQ-resistance was related to the increase in use remains to be evaluated.

T293

138195-138266

Epistemic_statement

denotes

The main goal is to preserve the effectiveness of antimicrobial agents.

T294

138983-139128

Epistemic_statement

denotes

Although the epidemic spread in southern Sweden of penicillin-resistant S. pneumoniae was curbed, the national frequency increased from 4% to 6%.

T295

139129-139221

Epistemic_statement

denotes

A hospital outbreak of MRSA could be terminated using aggressive infection-control measures.

T296

139449-139630

Epistemic_statement

denotes

Despite this, antibiotic resistance in several bacterial species is slowly increasing which calls for continued sustained efforts to preserve effectiveness of available antibiotics.

T297

141853-141994

Epistemic_statement

denotes

There is limited variation in the use of different antibiotic groups in most hospitals -a risk factor for emergence of antibiotic resistance.

T298

142588-142847

Epistemic_statement

denotes

The four scales were: attitudes towards appropriateness of self-medication with antibiotics for bronchitis, beliefs about antibiotics for minor ailments, attitudes towards situational use of antibiotics and knowledge about antibiotics and viruses or bacteria.

T299

142923-143211

Epistemic_statement

denotes

Analysis: To deal with the possible confounding effect of both use of selfmedication and education, we performed stratified analyses, i.e., we studied the differences between countries separately for users and non-users of self-medication, and for respondents with high and low education.

T300

143454-143535

Epistemic_statement

denotes

To limit this increase the appropriate use of ciprofloxacin should be encouraged.

T301

145739-145942

Epistemic_statement

denotes

There was a trend towards a greater rise in creatinine in Group 2 versus Group 1: final creatinine increased by 88% vs 52% from baseline (p = 0.08), which was reversible on stopping study drug treatment.

T302

147882-148050

Epistemic_statement

denotes

Clinicians should be aware that C. gattii can be acquired in Canada and that the epidemiological and clinical characteristics of this disease differ from C. neoformans.

T303

148051-148193

Epistemic_statement

denotes

Objectives: The incidence of invasive zygomycosis (IZ) appears to be increasing, especially in patients treated for haematological malignancy.

T304

148194-148363

Epistemic_statement

denotes

Presently, no biological markers exsist that facilitate early diagnosis, and one has to rely on conventional diagnostic methods, such as culture, which lack sensitivity.

T305

149633-149756

Epistemic_statement

denotes

Conclusion: zAg and zygomycete DNA are present in BALF of patients with IZ, and might be a useful tool for early diagnosis.

T306

149757-149933

Epistemic_statement

denotes

The presence of both markers in BALF samples from high-risk patients without a clinically manifest disease might indicate the presence of colonisation or subclinical infection.

T307

150017-150080

Epistemic_statement

denotes

However, differences were detected between the different media.

T308

151004-151139

Epistemic_statement

denotes

Simultaneously with the increased expression of gapB, PIA production could be visualised through CLSM in sessile bacteria in all media.

T309

151375-151600

Epistemic_statement

denotes

The persistent expression of gapA in sessile bacteria could indicate a role in biofilm formation, especially in the early stages, while expression levels of gapB could indicate a role in the later phases of biofilm formation.

T310

151601-151727

Epistemic_statement

denotes

Results of gene expression and CLSM indicate a link between gapB and PIA production that is influenced by both Fe and glucose.

T311

151852-152026

Epistemic_statement

denotes

Purportedly, the uropathogenicity of S. saprophyticus can be attributed to its ability to cope with the high range of variation in salt-and urea-concentration in human urine.

T312

152027-152104

Epistemic_statement

denotes

The aim of this study was to elucidate virulence factors of uropathogenicity.

T313

152882-153041

Epistemic_statement

denotes

The biofilm formation in S. saprophyticus seems independent of agr-, Ssp-, SdrI, since no difference between knockout mutants to wild type strain was observed.

T314

153042-153111

Epistemic_statement

denotes

Conclusion: Bacterial aggregation could be due to increased adhesion.

T315

153112-153178

Epistemic_statement

denotes

The lipase activity may modulate hydrophobicity and Ca 2+ binding.

T316

153179-153300

Epistemic_statement

denotes

Higher local Ca 2+ concentration, as well as strengthened bacterial aggregation, may lead to increased crystal formation.

T317

153301-153395

Epistemic_statement

denotes

Bacteria may adhere to crystals, additionally to the later mechanism due to biofilm formation.

T318

153475-153527

Epistemic_statement

denotes

This may be a new model of infectious stone genesis.

T319

153528-153767

Epistemic_statement

denotes

This study strongly suggest that S. saprophyticus wild-type strain CCM 883 lacks important virulence factors in contrast to wild-type strain 7108 and biofilm formation may play an important role in S. saprophyticus urinary tract infection.

T320

153768-153981

Epistemic_statement

denotes

Objectives: The influence of biofilm formation in catheter-related candidiasis has been established and it has been shown that the development of biofilm by the colonising yeasts confers resistance to antifungals.

T321

154140-154239

Epistemic_statement

denotes

Methods: An in vitro model of C. albicans biofilm associated with 100% silicone catheters was used.

T322

155006-155223

Epistemic_statement

denotes

Conclusions: These preliminary results suggest that this new molecule, naturally produced within yeasts communities, could be a good candidate for the prevention of biofilms associated with indwelling medical devices.

T323

155523-155654

Epistemic_statement

denotes

Its immunogenicity and specificity led to a series of studies to assess its potential as a major component of new diagnostic tests.

T324

156126-156263

Epistemic_statement

denotes

It is clear that these tests are not confounded by prior BCG vaccination and are probably not subject to boosting by injected tuberculin.

T325

156264-156363

Epistemic_statement

denotes

Their quantitative readouts may also provide important information with respect to infectious load.

T326

156364-156600

Epistemic_statement

denotes

However, some findings have caused concern: disparity in test performance between temperate non-TB endemic and tropical TB-endemic settings, evidence of relatively poor sensitivity to the presence of certain M. tuberculosis strains (eg.

T327

156646-156719

Epistemic_statement

denotes

Pulmonary TB, certain TB contacts), and rapid unexplained test reversion.

T328

156720-156944

Epistemic_statement

denotes

It is therefore becoming clear that T cell assays may have a niche in the diagnosis of certain TB cases and in certain individuals suspected of having M. tuberculosis infection, but this niche has not yet been fully defined.

T329

156945-157056

Epistemic_statement

denotes

More longitudinal studies, especially following TB case contacts for the development of disease, are indicated.

T330

157057-157116

Epistemic_statement

denotes

Also more studies should be undertaken in TB endemic areas.

T331

157117-157241

Epistemic_statement

denotes

Finally, if these tests are to have any role in TB control globally they would need to be much cheaper and more easy to use.

T332

157315-157474

Epistemic_statement

denotes

Over the last ten years unprecedented progress has been made in the treatment of HIV infection by the application of combination antiretroviral therapy (cART).

T333

157767-157856

Epistemic_statement

denotes

During the last year a whole bundle of drugs with new targets has been studied in humans.

T334

158052-158170

Epistemic_statement

denotes

It is expected, that integrase inhibitors and CCR5-antagonists will be introduced into clinical practice in 2007/2008.

T335

158578-158675

Epistemic_statement

denotes

Preliminary data also suggest a high virological potency of the drug in treatment naïve patients.

T336

158860-159060

Epistemic_statement

denotes

Vicriviroc together with OBT has shown superiority over OBT alone in treatment experienced patients, but has failed in a phase II study in treatment naïve patients presumably due to matters of dosing.

T337

159061-159152

Epistemic_statement

denotes

Further studies to define the optimal dose (together with ritonavir boosting) are underway.

T338

159529-159660

Epistemic_statement

denotes

Since these drugs seem to be very well tolerated there is also a potential for their use in treatment naïve patients in the future.

T339

159820-159971

Epistemic_statement

denotes

Current antiretroviral regimens however cannot achieve virus eradication and virological rebound virtually always occurs after therapy discontinuation.

T340

159972-160072

Epistemic_statement

denotes

Long-term highly active antiretroviral therapy (HAART) is life saving, but poses several challenges.

T341

160073-160198

Epistemic_statement

denotes

Potential adverse events can be categorised as problems related to adherence, pharmacokinetics, toxicity and drug resistance.

T342

160199-160502

Epistemic_statement

denotes

Various interventions have been explored to improve and maintain good adherence among treated individuals, ranging from treatment simplification strategies to addressing mental health problems, and a major challenge is related to the need for integrated biomedical, social and behavioural interventions.

T343

160503-160610

Epistemic_statement

denotes

Inadequate adherence however accounts for only a subset of subtherapeutic drug levels in clinical practice.

T344

160611-160810

Epistemic_statement

denotes

There is a significant degree of inter-individual variability in absorption, metabolism and cellular transport of antiretroviral drugs, with potential impact on both efficacy and toxicity of therapy.

T345

160897-161017

Epistemic_statement

denotes

Although evidence of the influence of pharmacogenomics is growing, there remain limited data to guide clinical practice.

T346

161018-161232

Epistemic_statement

denotes

Proton pump inhibitors are an example of commonly prescribed medications that can affect antiretroviral drug levels by reducing the absorption of certain protease inhibitors (PIs) and increasing exposure to others.

T347

161233-161366

Epistemic_statement

denotes

Herbal medicines such as St. John's wort, widely used by HIV patients, also have the potential to interact with antiretroviral drugs.

T348

161367-161497

Epistemic_statement

denotes

Thus, patient education and good communication across care providers are paramount to prevent unfavourable drug-drug interactions.

T349

161498-161648

Epistemic_statement

denotes

The risk of toxicity associated with long-term antiretroviral therapy is difficult to predict reliably in an aging population of HIV-infected persons.

T350

161924-162159

Epistemic_statement

denotes

The risk of cardiovascular disease is a particular concern, due to the combined effects on the cardiovascular system of HIV infection, HAART and lifestyle related risk factors such as smoking which are common among HIVinfected persons.

T351

162387-162488

Epistemic_statement

denotes

However, drug resistance continues to emerge as a result of problems with adherence and tolerability.

T352

162794-162923

Epistemic_statement

denotes

New drugs and drug classes are required to optimise treatment among drug-experienced persons and reduce the risk of side effects.

T353

163183-163281

Epistemic_statement

denotes

In spite of these concerns however, the benefits of HAART far outweigh the risk of adverse events.

T354

163282-163418

Epistemic_statement

denotes

The results strongly suggest that keratinocytes are able to produce cytokines in response to L. major stimulation through in part-TLR-2.

T355

163419-163774

Epistemic_statement

denotes

Aspergillus fumigatus, a termotolerant saprophyte, is associated with a wide spectrum of diseases in humans, that includes saprophytic colonisation of preexisting cavities, allergic asthma, allergic bronchopulmonary aspergillosis occurring as a complication of bronchial asthma or cystic fibrosis, and invasive aspergillosis in immunocompromised patients.

T356

163915-164156

Epistemic_statement

denotes

The inherent resistance to diseases caused by A. fumigatus suggests the occurrence of regulatory mechanisms that provide the host with adequate defence without necessarily eliminating the fungus or causing unacceptable levels of host damage.

T357

165491-165651

Epistemic_statement

denotes

These studies will illustrate how studying the structure and function of these molecules is increasing our understanding of virus pathogenesis and cell biology.

T358

165890-166025

Epistemic_statement

denotes

The complex situation of malaria transmission in various endemic areas requires differentiated recommendations for malaria prophylaxis.

T359

166080-166219

Epistemic_statement

denotes

Malaria risk can be reduced by compliant exposure prevention, and with chemoprophylactic drugs for travel to high risk areas are available.

T360

166442-166502

Epistemic_statement

denotes

The importance of exposure prophylaxis should be emphasized.

T361

166503-166607

Epistemic_statement

denotes

It is recommended to use mosquito repellents after dusk, especially if outdoor activities are performed.

T362

166608-166717

Epistemic_statement

denotes

Light-coloured, loose-fitting insecticide-treated clothing with long trousers and long sleeves are suggested.

T363

166718-166862

Epistemic_statement

denotes

Sleeping under insecticide treated bed nets or in airconditioned rooms which are pre-treated with insecticides (knockdown spray) is recommended.

T364

166863-166914

Epistemic_statement

denotes

Chemoprophylaxis is recommended in high risk areas.

T365

167038-167162

Epistemic_statement

denotes

In German speaking countries, emergency treatment is recommended for trips to regions with low or intermediate malaria risk.

T366

167163-167267

Epistemic_statement

denotes

This strategy is recommended when the infection risk is lower than the risk of severe drug side effects.

T367

167540-167729

Epistemic_statement

denotes

The guidelines for the application of the emergency-self-treatment should be discussed thoroughly with the traveller, to make sure that in case of fever the correct action will be taken: 1.

T368

167730-167918

Epistemic_statement

denotes

In case of fever (sudden onset or rapidly progressive) -axillary temperature >37.5ºC (oral, tympanal or rectal >38ºC) -a doctor should be seen and a malaria blood test should be performed.

T369

167973-168100

Epistemic_statement

denotes

If no doctor can be seen within 24h and the traveller is in an endemic region for at least 6 days, the fever should be lowered.

T370

168104-168184

Epistemic_statement

denotes

The malaria emergency medication should be taken with adequate amounts of fluid.

T371

168188-168302

Epistemic_statement

denotes

In every case, also after the intake of the malaria drug a doctor must be consulted at the earliest possible time.

T372

169059-169192

Epistemic_statement

denotes

The initially asymptomatic liver disease is still rare in Central Europe, and diagnosis is often made at a late stage of the disease.

T373

169618-169714

Epistemic_statement

denotes

However, the expertise of the radiologist is often not available due to the low incidence of AE.

T374

169715-169788

Epistemic_statement

denotes

Serology is helpful, but may be misleading due to non-standardised tests.

T375

170074-170179

Epistemic_statement

denotes

Filarial worm infections of humans cause morbidity and even death in developing countries of the tropics.

T376

170303-170487

Epistemic_statement

denotes

Another problem with controlling filarial infections is the lack of any alternative drugs that can be used in the current mass drug administration programmes should resistance develop.

T377

170913-171118

Epistemic_statement

denotes

Targeting of Wolbachia with antirickettsial drugs has lead to the recommendation of doxycycline for use on an individual basis and may be recommended in areas where resistance to current drugs may develop.

T378

171285-171469

Epistemic_statement

denotes

Research is underway to discover new drugs, preferably those already approved for use in humans, that have antiwolbachial activity and work in a shorter time and are widely applicable.

T379

173194-173317

Epistemic_statement

denotes

However, while the vegetation counts of the parent increased at 48, 72 and 120 h, the counts of GISA M1V16 remained stable.

T380

173518-173583

Epistemic_statement

denotes

This might explain its clustering in immuno-compromised patients.

T381

173584-173708

Epistemic_statement

denotes

Whether a very prolonged exposure to glycopeptides might restore pathogenicity and fitness defects remains to be determined.

T382

174079-174396

Epistemic_statement

denotes

In order to investigate whether the declined ability of the PFGEidentical isolates to form biofilm in vitro correlated to pathogenicity in vivo, 5 non-mucoid clones from 1980 and 1988 (early clones), and 1997, 1999 and 2003 (late clones) embedded in alginate were installed in the lungs of five groups of BALB/c mice.

T383

175837-176022

Epistemic_statement

denotes

While the exact mechanism remains to be fully elucidated, this demonstrates the validity of using commensal lactic acid bacteria strains in the prevention of gastrointestinal infection.

T384

176119-176470

Epistemic_statement

denotes

While the probiotics examined in this study are of obvious interest to those involved in the pig production industry, the similarities between the pig and human gastrointestinal tracts suggest that the probiotics offer potential in cases of human salmonellosis, given that the methodology used is also likely to be applicable to human disease control.

T385

176597-176710

Epistemic_statement

denotes

Such resistances have frequently been associated with strains that produce extendedspectrum b-lactamases (ESBLs).

T386

176711-177001

Epistemic_statement

denotes

As Salmonella with resistance to quinolone antimicrobials have become increasingly common in isolates from humans in England and Wales, a study has been initiated to investigate the occurrence of such genes in isolates from humans and food, and to assess their importance for public health.

T387

177652-177956

Epistemic_statement

denotes

Of these the isolates of Stanley and Typhimurium were from patients infected abroad, the isolate of Virginia was from a patient who had not travelled abroad, and the two isolates of Virchow, one from imported frozen chicken and one from a patient were associated with a series of infections in 2003/2004.

T388

178410-178548

Epistemic_statement

denotes

These results indicate that plasmidic quinolone resistance, often linked to other resistances, has now appeared in S. enterica in Britain.

T389

178549-178653

Epistemic_statement

denotes

This is of particular concern for the treatment of infections with invasive serovars such as S. Virchow.

T390

178654-178813

Epistemic_statement

denotes

Objective: The rapid characterisation of (drug-resistant) Mycobacterium tuberculosis (MTB) would be useful for the research and treatment of tuberculosis (TB).

T391

178814-178963

Epistemic_statement

denotes

Many important genetic markers of MTB have been identified, notably for drug resistance, but also genotype, bacterial lineage and adaptive potential.

T392

178964-179046

Epistemic_statement

denotes

A single assay allowing identification of these markers would aid control efforts.

T393

179288-179524

Epistemic_statement

denotes

We explored the utility of MLPA as a screening tool to rapidly characterise MTB-strains Method: MLPA can identify multiple single nucleotide polymorphisms (SNPs) by amplification of sequence-specific MLPA-probes, rather than target DNA.

T394

180200-180310

Epistemic_statement

denotes

To determine the predictive value of MTB-specific MLPA, we screened DNA of MTB-strains with unknown genotypes.

T395

180349-180440

Epistemic_statement

denotes

There was a very high correlation between sequencing results and results obtained via MLPA.

T396

180571-180725

Epistemic_statement

denotes

We have shown that with MTB-specific MLPA it is possible to identify drug resistance associated mutations and MTB lineage specific SNPs in a single assay.

T397

180726-180853

Epistemic_statement

denotes

Depending on the application, probes can be added to or removed from the probe-mix, making it a flexible, multi-purpose method.

T398

180854-180990

Epistemic_statement

denotes

MLPA products can be easily identified on an agarose-gel, making it especially suitable for screening of TB in the less-developed world.

T399

181381-181892

Epistemic_statement

denotes

Yet, there is a known disparity between fluoroquinolone-susceptible and -resistant isolates, which it is assumed has arisen from the susceptible population: Only a small proportion of resistant isolates belong to group B2, while the majority belong to group D. For a possible explanation of the disparate distribution among phylogenetic groups this work analysed ciprofloxacin-susceptible and -resistant ICU isolates in all phylogenetic groups for differences in virulence factors (VF) and mutation frequencies.

T400

182089-182327

Epistemic_statement

denotes

In order to compare isolates from different groups and susceptibilities, a similar and as large a number as possible of susceptible and resistant strains were chosen randomly from groups A (23; 27), B1 (7; 11), B2 (17; 9), and D (15; 25).

T401

182999-183172

Epistemic_statement

denotes

However, there was a small, but significant difference in the median of the mutation rates between the isolates of different groups, increasing in the order B2 < D < B1 < A.

T402

183351-183557

Epistemic_statement

denotes

Conclusion: Slightly, but significantly reduced mutation rates in strains of the deep rooted phylogenetic group B2 might be an explanation for their rare occurrence among fluoroquinolone-resistant isolates.

T403

183655-183820

Epistemic_statement

denotes

The aim of this study was to understand evolution of CAZ resistance among CAZ susceptible ESBL belonging to this cluster by step-wise in vitro selection experiments.

T404

184872-185035

Epistemic_statement

denotes

Interestingly, and with exception of two variants and CXM, a concomitant loss of resistance to all other antibiotics tested (antagonistic pleiotropy) was observed.

T405

185252-185330

Epistemic_statement

denotes

However, D240G change determined a lower decrease to FEP and CXM than P167S/T.

T406

185898-186018

Epistemic_statement

denotes

A77V could be a secondary mutation site affecting CAZ or could be involved in re-equilibrium of CTXR/CAZR co-resistance.

T407

186297-186536

Epistemic_statement

denotes

The new respiratory's FQs, levofloxacin (LEV) and moxifloxacin (MOX), retain their activity against these first-step parC mutants, although there are concerns that their widespread use might select for second-step, high-level FQ-R mutants.

T408

187609-187828

Epistemic_statement

denotes

However, an emm6 throat isolate, recovered from a 36-year old female in 2005, exhibited highlevel resistance to CIP (MIC 32 mg/mL), full resistance to LEV (MIC 8 mg/mL) and decreased susceptibility to MOX (MIC 1 mg/mL).

T409

190690-190865

Epistemic_statement

denotes

This will be an important prerequisite for definition of isolates as identical, related of different, which is essential for successful epidemiological outbreak investigation.

T410

191376-191511

Epistemic_statement

denotes

higher temperature, higher polymorphonuclear counts and complications are more frequent), but NTHi can still cause significant disease.

T411

191512-191677

Epistemic_statement

denotes

The role of NTHi in recurrent and non-responsive AOM in both infants and in older children is recognized, suggesting different biological pathways compared with Pnc.

T412

191904-191990

Epistemic_statement

denotes

The role of NTHi in LRIs in general, and in pneumonia in particular, is not yet clear.

T413

191991-192050

Epistemic_statement

denotes

In cystic fibrosis, however, NTHi is an important pathogen.

T414

192051-192344

Epistemic_statement

denotes

Although H. influenzae type b disease has practically been eliminated in vaccinated populations, the picture with S. pneumoniae in the 7-valent Pneumococcal Conjugate Vaccine (PCV7) era is much more complex owing to its limited serotype coverage and some replacement with nonvaccine serotypes.

T415

192345-192482

Epistemic_statement

denotes

A vaccine with additional pneumococcal serotypes and activity against NTHi would be a very welcome addition to our vaccine armamentarium.

T416

192483-192611

Epistemic_statement

denotes

Otitis media (OM) is a highly prevalent paediatric disease that is associated with significant morbidity and socioeconomic cost.

T417

192816-193043

Epistemic_statement

denotes

Despite their similar roles as opportunistic pathogens of the middle ear, the pathogenic mechanisms utilised by these bacteria (nontypeable Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis) are unique.

T418

193747-194049

Epistemic_statement

denotes

In the past few years it has been demonstrated that each of the three predominant bacteria involved in OM can form a biofilm in in vitro assay systems and in animal models, and that they participate in biofilms formed on middle ear mucosa specimens recovered from children with recurrent or chronic OM.

T419

194274-194586

Epistemic_statement

denotes

It is particularly intriguing that some of the paediatric middle ear mucosa-derived biofilms characterised were of mixed bacterial aetiology, suggesting that progress made on single-microbe directed strategies for the treatment and/or prevention of OM, while highly encouraging, are also likely to be inadequate.

T420

194587-194943

Epistemic_statement

denotes

Therefore, a significantly greater understanding of how microbial physiology relates to the involvement of biofilms in OM is required to identify points in the disease course that are perhaps more amenable to treatment strategies, and also biofilm-relevant antigenic targets that would be helpful in the rational design of vaccine candidates to prevent OM.

T421

195100-195259

Epistemic_statement

denotes

Evidence suggests that PD is involved in the pathogenesis of respiratory tract infections, and has been implicated in NTHi adhesion and invasion of host cells.

T422

195260-195529

Epistemic_statement

denotes

An isogenic PD-deficient NTHi-mutant, compared with the wild type strain, had an approximately 100-fold lower capacity to cause acute otitis media (OM) in rats and induced significantly less impairment of ciliary function in a human nasopharyngeal tissue culture model.

T423

195530-195747

Epistemic_statement

denotes

The likely mechanism of pathogenicity is that PD is an enzyme (glycerophosphodiester phosphodiesterase, GlpQ) that releases phosphorylcholine (ChoP) from host epithelial cells to the lipooligosaccharide (LOS) on NTHi.

T424

195748-195922

Epistemic_statement

denotes

LOS-ChoP interacts with platelet-activating factor receptors, inhibiting ciliary beat frequency of human bronchial epithelial cells and activating G protein-related pathways.

T425

196857-196977

Epistemic_statement

denotes

Large efficacy trials are not feasible any more, and the acceptance of the new PCVs will rely on immunogenicity studies.

T426

197256-197492

Epistemic_statement

denotes

The protective functional mechanism of antibodies to pneumococcal capsular polysaccharides resides in opsonophagocytosis and the demonstration of the opsonophagocytic activity (OPA) has been regarded as an important secondary threshold.

T427

197493-197605

Epistemic_statement

denotes

Thus far there are only few published PCV efficacy trials that connect with OPA data and their good correlation.

T428

197760-198012

Epistemic_statement

denotes

In general, the OPA titers and the antibody concentrations correlate well, but different serotypes can show various OPA/EIA ratios meaning that for certain serotypes (like 19F or 1) more antibodies are needed for killing the bacteria than for the rest.

T429

198013-198207

Epistemic_statement

denotes

Importantly, the elderly and HIV positive patients seem to have antibodies of low functional activity, and measuring OPA in studies in the elderly and HIV patients has been considered important.

T430

198400-198537

Epistemic_statement

denotes

Measuring OPA with the classical killing assay consumes serum and time and thus measuring OPA for large materials is not always feasible.

T431

198538-198680

Epistemic_statement

denotes

However, the development of multiplex and/or high throughput assays will end up in wider use of this technology in the future clinical trials.

T432

198681-198815

Epistemic_statement

denotes

This would be in concordance with the guidelines for evaluation meningococcal conjugate vaccines by serum bactericidal activity assay.

T433

199238-199651

Epistemic_statement

denotes

More than 90 serotypes of pneumococci exist, but only 10 serogroups appear to be responsible for 80-85% of invasive pneumococcal disease and pneumococcal otitis media (OM) worldwide, ranging from the relatively rare but clinically severe meningitis, to the more frequent infections of the bloodstream and the lungs, such as pneumonia and finally to the extremely common middle ear infections among young children.

T434

199652-199801

Epistemic_statement

denotes

Middle ear infections are often associated with diagnostic uncertainty, frequent use and misuse of antibiotics, and recurrent and persistent disease.

T435

199876-199992

Epistemic_statement

denotes

Recurrent and persistence disease can lead to temporary or even permanent hearing loss and surgery (tube placement).

T436

199993-200187

Epistemic_statement

denotes

In order to address these issues, preventive acute OM (AOM) strategies should include a vaccine with broader pneumococcal serotype coverage as well as protection against additional otopathogens.

T437

201234-201571

Epistemic_statement

denotes

Patients infected with 027 strain were likely to have a more severe disease (RR = 1.72, 95% CI: 1.07−2.75, p = 0.048), to have received less antimicrobials in the month preceding diarrhoea (RR = 0.76, 95% CI: 0.53−1.10, p = 0.05) and to have been more specifically treated by metronidazole or vancomycin (RR = 1.32, 1.17−1.49, p = 0.02).

T438

201779-201864

Epistemic_statement

denotes

The incidence and severity of nosocomial C. difficile disease seems to be increasing.

T439

202160-202247

Epistemic_statement

denotes

Described changes correlate with changed populations of C. difficile present in humans.

T440

202248-202471

Epistemic_statement

denotes

New type BI/NAP1/027 with increased virulence is spreading since 2003, but only part of the recent increase in mortality and morbidity caused by C. difficile infections can be accounted for by this new highly virulent type.

T441

202561-202750

Epistemic_statement

denotes

Such binary toxin positive strains used to be more often associated with animal than human host and early typing comparisons did not show many similarities between human and animal strains.

T442

202751-202900

Epistemic_statement

denotes

However, recent studies found a marked overlap between isolates from calves and humans, including two of the predominant outbreak types, 027 and 017.

T443

202901-203056

Epistemic_statement

denotes

C. difficile has also been found in retail meat samples, suggesting that food could be involved in the transmission of C. difficile from animals to humans.

T444

203429-203852

Epistemic_statement

denotes

The infection control measures include recommendations to isolate infected patient on a single room with designated toilet, to apply proper hand hygiene with soap and water, to use appropriate protective clothing (gloves and aprons or gowns), to intensify environmental cleaning with a chlorine containing disinfectant and to take specific precautions for the use of devices (disposable or dedicated to individual patient).

T445

203922-204051

Epistemic_statement

denotes

Each hospital should have an appropriate surveillance system to recognize an increase of the incidence of CDAD in an early stage.

T446

204052-204206

Epistemic_statement

denotes

All infection control measures should be written in a local protocol so that additional measures can be carried out as soon as a problem with CDAD arises.

T447

204207-204620

Epistemic_statement

denotes

When outbreaks occur, additional recommendations include a reinforcement of general and hand washing measures, intensifying of testing patients with diarrhoea for C. difficile, reinforcement of environmental cleaning, information and education of healthcare workers, cleaning department and visitors, cohorting of infected patients, and eventually closure of the unit followed by intensive environmental cleaning.

T448

204621-204736

Epistemic_statement

denotes

Restricted antibiotic prescribing is also highly recommended to reduce polypharmacy and duration of administration.

T449

204737-204876

Epistemic_statement

denotes

Second and third generations cephalosporins, clindamycin and more recently fluoroquinolones have been identified as potential risk factors.

T450

204877-205096

Epistemic_statement

denotes

Although some hospitals report successes for enhanced environmental cleaning with potentially effective agents such as hydrogen peroxide vapour, the evidence is too scarce to consider this as an evidence-based approach.

T451

205430-205516

Epistemic_statement

denotes

However, Acinetobacter infections can also be acquired outside the healthcare setting.

T452

205769-205918

Epistemic_statement

denotes

Most of the latter reports originate from tropical or sub-tropical areas, and may become more common following ongoing changes in the global climate.

T453

206228-206355

Epistemic_statement

denotes

A recent increase in the number of carbapenem-resistant strains, particularly in eastern Europe, is currently of great concern.

T454

206356-206620

Epistemic_statement

denotes

The recent EU-funded ARPAC study revealed that 130 of 169 participating European hospitals in 32 European countries had encountered carbapenem-resistant isolates of Acinetobacter, ranging from very rare sporadic resistant isolates to an endemic/epidemic situation.

T455

207050-207325

Epistemic_statement

denotes

Three 'European Clones' (lineages) have been identified in hospitals throughout Europe, but numerous other, more localised, clones have also been characterised, showing that the problem of A. baumannii is not confined solely to the widespread 'European clones I, II and III'.

T456

207326-207434

Epistemic_statement

denotes

The reasons why certain A. baumannii lineages are more successful than others are not understood at present.

T457

207435-207590

Epistemic_statement

denotes

Overall, the available epidemiological evidence suggests that A. baumannii is becoming one of the most significant microbial challenges of the current era.

T458

207591-207814

Epistemic_statement

denotes

Strains in some hospitals are already effectively untreatable, and more scientific efforts and resources are urgently needed to further elucidate the epidemiological and infection control issues related to these infections.

T459

207948-208124

Epistemic_statement

denotes

Whereas A. baumannii has itself a quite high level of naturallyoccurring antibiotic resistance, it may acquire additional resistance traits as a source of multidrug resistance.

T460

208125-208203

Epistemic_statement

denotes

These resistance mechanisms may involve most of the antibiotic molecules, i.e.

T461

208331-208445

Epistemic_statement

denotes

A similar trend between the number of A. baumannii infections and antibiotic resistance may be observed worldwide.

T462

209121-209310

Epistemic_statement

denotes

The patient's urine was tested positive for Lassa virus, which was taken into account for the risk assessment and contributed to the decision to trace back copassengers potentially exposed.

T463

210044-210224

Epistemic_statement

denotes

Our best estimate for the initial reproduction number (R 0 ) was 3.7, although it could range from 2 to 11 depending on assumptions regarding incubation and lifespan in mosquitoes.

T464

210225-210374

Epistemic_statement

denotes

In the best fitting case, each infected individual may have contaminated 3 mosquitoes at most, and each mosquito contaminated 1.4 persons on average.

T465

210375-210559

Epistemic_statement

denotes

Using data from the first season alone, modelbased extrapolations suggested that epidemic outbreaks were possible as long as more than one third of the population remained susceptible.

T466

210560-210795

Epistemic_statement

denotes

Conclusion: Despite a thousand-fold change in incidence between the two seasons, the transmission characteristics of Chikungunya were similar; therefore there is no epidemiological evidence for an increase in virulence between seasons.

T467

210796-210967

Epistemic_statement

denotes

At a time when information systems make it easier to monitor the course of emerging diseases, methods for timely and efficient analysis of the data must also be developed.

T468

212048-212185

Epistemic_statement

denotes

Further research is needed to determine sequelae, risk factors, outbreak potential, and the utility of chemoprophylaxis for this disease.

T469

212521-212721

Epistemic_statement

denotes

Previous studies with methicillin-resistant Staphylococcus aureus (MRSA) revealed that telavancin increases cell membrane permeability and causes rapid dissipation of the bacterial membrane potential.

T470

212865-212993

Epistemic_statement

denotes

Methods: Cell membrane potential and membrane permeability were studied in telavancin-treated S. aureus ATCC 33591 (MRSA) cells.

T471

212994-213117

Epistemic_statement

denotes

The fluorescent dyes, DiOC2(3) and propidium iodide, were used to assess membrane potential and permeability, respectively.

T472

213203-213334

Epistemic_statement

denotes

Results: Telavancin (MIC, 0.5 mg/mL) caused a concentration-and time-dependent dissipation of the membrane potential in MRSA cells.

T473

213769-214003

Epistemic_statement

denotes

Conclusion: Exposure of MRSA cells to telavancin initiated concentration-and time-dependent membrane depolarisation and increases in permeability, further demonstrating that telavancin interferes with bacterial cell membrane function.

T474

214603-214816

Epistemic_statement

denotes

In vitro studies suggest that TLV exhibits superior antibacterial potency relative to vancomycin (VAN); this may be due to the lipophilic decylaminoethyl side chain that targets TLV to the bacterial cell membrane.

T475

215153-215337

Epistemic_statement

denotes

Susceptibility or inducible resistance to oleandomycin was associated with the presence of an inducible erm(A) or erm(C) gene, respectively and might constitute markers of these genes.

T476

215338-215506

Epistemic_statement

denotes

The risk analysis for the clindamycin use in therapy of infections due to S. aureus inducibly resistant to erythromycin might include the nature of the resistance gene.

T477

219840-220009

Epistemic_statement

denotes

These data could provide further evidence about the possible role of pentapeptidic proteins of different Gram-positive species in their natural resistance to quinolones.

T478

220010-220110

Epistemic_statement

denotes

These Gram positives species could constitute a reservoir of Qnr-like quinolone resistance proteins.

T479

220301-220378

Epistemic_statement

denotes

However, it is unknown whether loss of K + is sufficient to cause cell death.

T480

220379-220526

Epistemic_statement

denotes

In this study we determined the kinetics of both cell death and lysis of S. aureus treated with DAP to establish any relationships between the two.

T481

222026-222188

Epistemic_statement

denotes

Conclusion: Our findings support the Silverman model for the mode of action of DAP and the hypothesis that it can cause rapid cell death without whole cell lysis.

T482

222189-222316

Epistemic_statement

denotes

We have, however, shown that cell lysis does occur over time, through both EM images and the leakage of large amounts of b-gal.

T483

222317-222482

Epistemic_statement

denotes

Our findings, while upholding the Silverman model, suggest that it is too simple to conclude that cell death is due only to loss of K + and membrane de-energisation.

T484

222483-222552

Epistemic_statement

denotes

The rapid loss of ATP would be an equally likely cause of cell death.

T485

222553-222944

Epistemic_statement

denotes

Objective: To study the effects of efflux pump inhibitors (CCCP and PAbN) on carbapenems in P. aeruginosa (Pa); to investigate the correlation between the resistance phenotypes and expression levels of efflux pumps of Pa and discuss the mechanism of different phenotypes in resistant Pa. By contrast, all the qnrA1-positive but blaVEB-1-negative isolates were negative for the A/C2 replicon.

T486

222945-223196

Epistemic_statement

denotes

These results clearly indicated that the genes encoding QnrA1 and VEB-1, when identified concomitantly in a given isolate, were always located on plasmids belonging to the same IncA/C2-incompatibility group that may vary in size and digestion pattern.

T487

223197-223291

Epistemic_statement

denotes

In addition, plasmids carrying the blaVEB-1 gene but lacking qnrA1 were also of the A/C2 type.

T488

223292-223472

Epistemic_statement

denotes

On the opposite, plasmids that were qnrA1-positive but blaVEB-1-negative were of distinct replicon types, suggesting independent acquisition of the qnrA gene on different plasmids.

T489

223473-223723

Epistemic_statement

denotes

Restriction pattern analysis of plasmid DNAs performed using the PstI endonuclease revealed that the blaVEB-1-positive plasmids exhibited different restriction profiles but also sharing common bands, likely corresponding to a common plasmid backbone.

T490

223724-223956

Epistemic_statement

denotes

Hybridisation performed with an A/C2-specific probe showed an identical signal revealing that the bands carrying the replication control region of the plasmids were of identical size, as expected with plasmids from the same lineage.

T491

223957-224100

Epistemic_statement

denotes

Conclusion: It is shown here that the IncA/C2 plasmid may be the main vehicle of the blaVEB-1 gene on which the QnrA1 determinant may be added.

T492

224101-224201

Epistemic_statement

denotes

Understanding these patterns will help to identify potential targets for public health intervention.

T493

224472-224731

Epistemic_statement

denotes

Using data obtained from a large test accuracy study into rapid detection of intrapartum GBS colonisation, the aims were to determine (1) the prevalence of vaginal and rectal GBS in labouring women, comparing standard culture to enrichment culture techniques;

T494

224732-225002

Epistemic_statement

denotes

(2) what proportion of women present with different risk factors; (3) how both culture positivity and risk factors correlate with the frequency of IAP administration; (4) baby colonisation rates with regard to maternal colonisation site and whether or not IAP was given.

T495

227906-228010

Epistemic_statement

denotes

The production of PVL seems to be the main factor that contributes to the course of acute osteomyelitis.

T496

229853-229958

Epistemic_statement

denotes

Conclusion: the present case shows that C-MRSA PVL-, tsst 1 might be associated with family transmission.

T497

229960-230107

Epistemic_statement

denotes

The prevalence of pathogenic Y. enterocolitica in Swiss pigs was high using PCR, however, the isolation rate was clearly lower than in German pigs.

T498

230408-230535

Epistemic_statement

denotes

The genetic diversity of ail-positive Y. enterocolitica in the pig tonsils collected from one Swiss slaughterhouse was limited.

T499

230536-230597

Epistemic_statement

denotes

T. van were significantly associated with the CDAD incidence.

T500

230818-230879

Epistemic_statement

denotes

Possibly, investigation at ward-level might correlate better.

T501

231349-231492

Epistemic_statement

denotes

The aim of this study is to examine the ability of A. castellanii to protect V. cholerae and to enhance its growth to be able to infect humans.

T502

232237-232430

Epistemic_statement

denotes

The antibiotic assay differentiated between extracellular bacteria that killed by gentamicin and intracellular bacteria that killed only by ciprofloxacin, which could diffuse into amoeba cells.

T503

233065-233288

Epistemic_statement

denotes

Free-living amoeba is a possible biological factor, which protects and enhances growth of V. cholerae to exceed its infections dose and to supports the idea of amoeba as a second host to the bacterium in nature besides man.

T504

233452-233569

Epistemic_statement

denotes

A primary trigger for these conditions is the complex microbiota found as dental plaque, a complex microbial biofilm.

T505

233796-234099

Epistemic_statement

denotes

One outcome of these advances is the realisation that periodontal diseases are associated with systemic conditions such as coronary heart disease and stroke; higher risk for preterm, low birth weight babies and pose threats to those with chronic disease: diabetes, respiratory diseases and osteoporosis.

T506

234205-234315

Epistemic_statement

denotes

The relationship between oral infections and systemic disease represents a paradigm shift in current research.

T507

234316-234459

Epistemic_statement

denotes

A portion of this lecture will be devoted to examining the role of chronic infections and their association with cardiovascular diseases (CVD).

T508

234637-234782

Epistemic_statement

denotes

Although a number of potential mechanisms have been postulated, the mechanism by which these infections are associated with CVD is still unclear.

T509

234783-235086

Epistemic_statement

denotes

The various hypotheses concerning this relationship include common susceptibility, inflammation via increased circulating cytokines and inflammatory mediators, direct infection of the blood vessels and finally the possibility of cross-reactivity or molecular mimicry between bacterial and self antigens.

T510

235391-235537

Epistemic_statement

denotes

While both medicine and dentistry are healthcare professions devoted to patient care, the interaction between the two disciplines remains limited.

T511

235538-235646

Epistemic_statement

denotes

It is rare for dental professionals to be integral members of medical teams or hospital/healthcare settings.

T512

236329-236500

Epistemic_statement

denotes

This session will highlight the unique oral care needs for our changing patient population, and how oral health can be improved when dentists and physicians work together.

T513

236799-236989

Epistemic_statement

denotes

The need for increased collaboration between dentists and physicians to prevent or reduce complications by maintaining better oral and medical health will form a core theme for this session.

T514

236990-237124

Epistemic_statement

denotes

It cannot be any longer ignored that oral health and medical health professionals must unite for optimal management of patient health.

T515

237486-237621

Epistemic_statement

denotes

An overview of clinically effective oral hygiene formulations and their role as therapeutic strategies will commence this presentation.

T516

237622-237881

Epistemic_statement

denotes

With triclosan serving as a case-study, the talk will bring together recent advances in the assessment of oral biofilms, analyses of clinical strains including susceptibility to demonstrate the microbiological safety and efficacy of oral hygiene formulations.

T517

238031-238273

Epistemic_statement

denotes

Whilst triclosan is not noted for its activity against enteric bacteria and pseudomonads, laboratory studies demonstrated that chronic sub-lethal exposure of Escherichia coli can select mutant clones with significantly reduced susceptibility.

T518

238407-238630

Epistemic_statement

denotes

Initial concern that mutations in FabI might be capable of horizontal transfer between environmental bacteria and noscomial pathogens or that parallel processes might occur directly in Gram-positive pathogens have subsided.

T519

238631-238789

Epistemic_statement

denotes

Similarly, concern about possible selection of resistance towards third-party agents (antibiotics) that might share the FabI gene target has proven unfounded.

T520

239001-239097

Epistemic_statement

denotes

Evidence suggests that efflux-on mutants are unable to compete in natural microbial communities.

T521

239098-239442

Epistemic_statement

denotes

Whilst there is insufficient evidence to suggest that the uncontrolled use of triclosan in domestic products is totally free of risk, its deployment for oral hygiene, especially where such use might limit the number of refractory infections and their possible complications contributes ultimately to a reduction in antibiotic use is encouraged.

T522

239443-239615

Epistemic_statement

denotes

Collectively, there is no evidence that the long-term application of triclosan formulations to the oral cavity or skin selects for triclosanresistant bacterial populations.

T523

239616-239810

Epistemic_statement

denotes

As the increasing elderly population retain more of their natural teeth into later life periodontal disease will pose an increasing problem both for the dentition and potentially general health.

T524

239811-240109

Epistemic_statement

denotes

The maintenance of an effective level of oral hygiene is the cornerstone of all attempts to prevent and control periodontal diseases and yet the widespread prevalence of these diseases indicates the inability of most people to achieve a level of plaque control commensurate with periodontal health.

T525

240528-240679

Epistemic_statement

denotes

These benefits were initially attributed to the antibacterial action of triclosan but evidence now suggests that it is also an anti-inflammatory agent.

T526

241644-241768

Epistemic_statement

denotes

Carbapenems have been shown to provide superior outcomes compared with other agents for infections caused by ESBL producers.

T527

241890-241968

Epistemic_statement

denotes

The major non-fermentative Gram-negative pathogen of concern is P. aeruginosa.

T528

242084-242288

Epistemic_statement

denotes

Initial therapy should include an antipseudomonal b-lactam, such as piperacillintazobactam, an antipseudomonal carbapenem, or an antipseudomonal cephalosporin, plus an aminoglycoside or a fluoroquinolone.

T529

242666-242807

Epistemic_statement

denotes

As antibiotic resistance increases, empiric therapy for severe infections should be based on local pathogen etiology and resistance patterns.

T530

242952-243068

Epistemic_statement

denotes

Carbapenems are likely to remain an important option for serious Gramnegative infections for the foreseeable future.

T531

243069-243303

Epistemic_statement

denotes

Since the number of new intravenous agents with activity against Gram-negative organisms is extremely limited, the development of a new carbapenem may help to reduce the mortality, morbidity, and cost of serious nosocomial infections.

T532

243850-243902

Epistemic_statement

denotes

Three carbapenem groups nevertheless can be defined.

T533

243903-244038

Epistemic_statement

denotes

Group 1 agents lack activity versus non-fermenters; they are represented by ertapenem and perhaps in the future also by oral analogues.

T534

244039-244285

Epistemic_statement

denotes

Ertapenem's utility lies in the treatment of community-acquired infections, where ESBL producers are likely or proven; it has convenient, oncedaily, dosing but is the most vulnerable carbapenem to combinations of ESBL or AmpC plus impermeability.

T535

244286-244503

Epistemic_statement

denotes

Group 2 comprises imipenem, meropenem, and doripenem, plus analogues available only in East Asia; they are active versus most non-fermenters and are appropriate in nosocomial settings where these pathogens are likely.

T536

244886-245030

Epistemic_statement

denotes

Imipenem resistance arises by loss of OprD alone and can be selected in therapy; nevertheless, imipenem is unique in evading pseudomonal efflux.

T537

245031-245389

Epistemic_statement

denotes

Meropenem and doripenem are relatively stable to renal dehydropeptidase, but imipenem needs protection with cilastatin; doripenem and meropenem are chemically stable, allowing prolonged infusion, whereas imipenem is not; doripenem and meropenem have little seizure potential (meropenem is licensed for meningitis), but CNS side-effects limit imipenem dosage.

T538

245660-245792

Epistemic_statement

denotes

As carbapenem usage expands, it is critical to understand these differences, so that the most appropriate analogues can be selected.

T539

245939-246231

Epistemic_statement

denotes

The goal of antimicrobial chemotherapy is to optimise the combined pharmacokinetic (PK) and pharmacodynamic (PD) profile of a drug so that the greatest percentage of patients achieves the PD target associated with a favourable outcome, while minimising the development of resistant organisms.

T540

246232-246489

Epistemic_statement

denotes

Integration of population PK, a PD target, and microbiologic surveillance data by Monte Carlo simulations can generate an empirical dosing strategy that maximises the likelihood that an antibiotic regimen achieves the desired PD end point (exposure target).

T541

246707-246878

Epistemic_statement

denotes

By extending the infusion period to achieve the necessary T > MIC, a lower dose can achieve the same efficacy as a higher dose, while lowering cost and potential toxicity.

T542

246879-247152

Epistemic_statement

denotes

For example, a recent publication showed that a 1-g 0.5-h infusion of meropenem has a 77.1% rate of target attainment against Pseudomonas aeruginosa isolated from hospitals in Hungary, whereas a 3-h infusion of 0.5 g meropenem would have an 83.8% rate of target attainment.

T543

247490-247639

Epistemic_statement

denotes

Doripenem is more stable upon reconstitution than other carbapenems, potentially making it more convenient and easier to use as an extended infusion.

T544

247939-248114

Epistemic_statement

denotes

Extended infusion of a lower dose of antibiotic may produce efficacy equivalent to shorter, higher-dose infusions while reducing both toxicity and the emergence of resistance.

T545

248115-248294

Epistemic_statement

denotes

Extended infusion of a carbapenem, such as doripenem, that has neither seizure potential nor high resistance selection is a particularly promising strategy for serious infections.

T546

248562-248813

Epistemic_statement

denotes

Doripenem's advantages over other carbapenems include: enhanced activity against Pseudomonas aeruginosa (with a low propensity for resistance), the lowest potential for seizures in the carbapenem class, and the greatest stability after reconstitution.

T547

250361-250463

Epistemic_statement

denotes

Serum and urine drug concentration data collected in Phase 1, 2, and 3 studies will also be discussed.

T548

250641-250803

Epistemic_statement

denotes

Doripenem's superior stability allowed the VAP trial to utilise an extended infusion (4-h) regimen for doripenem that may maximise for these difficult infections.

T549

251162-251283

Epistemic_statement

denotes

Hence: (i) M. tuberculosis can be controlled (though not eradicated) by the immune response induced by natural infection;

T550

251284-251404

Epistemic_statement

denotes

(ii) BCG fails to induce a protective immune response at least in those individuals who are susceptible to tuberculosis.

T551

251405-251498

Epistemic_statement

denotes

Current vaccination strategies have to consider both pre-exposure and post-exposure vaccines.

T552

251718-251804

Epistemic_statement

denotes

Antigens of M. tuberculosis also stimulate CD8 T cells, probably through crosspriming.

T553

251805-251899

Epistemic_statement

denotes

In addition, unconventional T cells also seem to participate in immunity against tuberculosis.

T554

251900-251946

Epistemic_statement

denotes

What can we learn for rational vaccine design?

T555

252660-252779

Epistemic_statement

denotes

Improved r-BCG should first be endowed with a higher immunogenicity and second may need a broader antigenic repertoire.

T556

252968-253153

Epistemic_statement

denotes

It is tempting to speculate that a prime/boost scheme comprising prime with improved r-BCG and boost with the most efficacious subunit vaccine candidate will provide optimal protection.

T557

253154-253341

Epistemic_statement

denotes

Identification of a biosignature that allows distinction between infection/protection and infection/disease in tuberculosis could speed up efficacy testing of vaccines in clinical trials.

T558

253342-253442

Epistemic_statement

denotes

The Grand Challenge 6 of the Bill & Melinda Gates Foundation aims at identifying such biosignatures.

T559

254057-254234

Epistemic_statement

denotes

The activity of the antimicrobial can therefore be studied both in vitro and in model systems, such as animal models, and a relationship between exposure and effect established.

T560

254235-254440

Epistemic_statement

denotes

The exposure is primarily determined by the pharmacokinetic characteristics of the drug, while the effect is determined by the concentration-effect relationship of the antimicrobial and the micro-organism.

T561

254441-254606

Epistemic_statement

denotes

However, in most clinical settings, it is the potency of the antimicrobial that is measured in terms of the MIC and not the concentration-effect relationship itself.

T562

254607-254706

Epistemic_statement

denotes

Therefore, a relationship needs to be ascertained between the MIC, exposure of the drug and effect.

T563

254707-254855

Epistemic_statement

denotes

Over the last decade, these pharmacokinetic/pharmacodynamic (PK/PD) relationships of antimicrobials have been established for most classes of drugs.

T564

254856-255126

Epistemic_statement

denotes

The two major indices describing these relationships are the time the concentration of the antimicrobial remains above the MIC (T >MIC) as a fraction of the dosing interval and the Area under the Time Concentration curve over 24 hours divided by the MIC (AUC/MIC ratio).

T565

255127-255294

Epistemic_statement

denotes

The Peak/MIC ratio correlates with effect for a number of drugs, but it in many, if not all, cases the effect can not be clearly distinguished from the AUC/MIC effect.

T566

255645-255858

Epistemic_statement

denotes

Importantly, it has been shown in a number of clinical trials -now exceeding 10 -including several classes of drugs, that the PK/PD relationships that do exist in animals are, as expected, similar to those in men.

T567

255859-255946

Epistemic_statement

denotes

Moreover, it has been shown that the quantitative relationships are remarkably similar.

T568

256253-256377

Epistemic_statement

denotes

In a relatively simple approach, these relationships are used in daily clinical practice in the use of clinical breakpoints.

T569

256749-256949

Epistemic_statement

denotes

More sophisticated, these relationships are used to adjust dosing regimens once the MICs of the infectious micro-organisms are known, and thus provide an integrated approach to the individual patient.

T570

257084-257243

Epistemic_statement

denotes

Alternatively, once dosing regimens are established, they can be used to form an opinion on the possible indications for various clinical treatment modalities.

T571

257244-257450

Epistemic_statement

denotes

Dissemination of microbial drug resistance observed in the antibiotic era is clearly related to the selective pressure generated by the use of antibiotics in clinical, veterinary and agricultural practices.

T572

257451-257736

Epistemic_statement

denotes

This notion is universally acknowledged and supported by the several studies that have correlated the emergence and dissemination of resistance with the use of new antibiotics, and by documentation of the absence of acquired resistance in clinical isolates from the pre-antibiotic era.

T573

257737-257937

Epistemic_statement

denotes

However, the presence of antibiotic-resistant bacteria has recently been reported also in humans and in wild animals living in remote areas where antibiotic exposure has been absent or minimal [1−3] .

T574

257938-258240

Epistemic_statement

denotes

This unexpected finding raises a question on the mechanisms responsible for spreading and maintenance of antibiotic resistance in similar settings, and could have important implications for the design of strategies addressed at controlling bacterial resistance based on antibiotic restriction policies.

T575

258241-258878

Epistemic_statement

denotes

Results of studies on antibiotic resistance in settings of minimal antibiotic exposure (including investigations recently carried out in very remote human communities living in the Bolivian Chaco and in the Alto Amazonas jungle of South America, and among wild reptiles (land iguanas) from a remote and protected island of the Galápagos archipelago with no documented sources of antibiotic exposure and minimum human contacts) will be critically reviewed in this presentation, and the mechanisms potentially involved in the dissemination of resistant strains and resistance genes unrelated to antimicrobial consumption will be discussed.

T576

258879-259119

Epistemic_statement

denotes

Results from the characterisation of resistance determinants carried by bacterial isolates from these settings pointed to their likely origin from antibiotic-exposed areas rather than to a local and independent resistance selection process.

T577

259120-259281

Epistemic_statement

denotes

However, the mechanisms responsible for this flow of resistance genes and for their maintenance and spread in absence of sustained antibiotic use remain elusive.

T578

260189-260458

Epistemic_statement

denotes

To determine whether the ChoP epitope was involved in the interaction of the P. aeruginosa isolates with the respiratory epithelial cells, standard invasion assays were performed using 16HBE14-bronchoepithelial cells, either treated or untreated with a PAFr antagonist.

T579

260914-261000

Epistemic_statement

denotes

We have demonstrated that in P. aeruginosa, the ChoP epitope is associated with EF-Tu.

T580

261249-261472

Epistemic_statement

denotes

Objectives: We aim to develop novel therapies for the treatment of Gram-negative bacterial infections, by isolating monoclonal antibodies that are capable of binding to signal molecules involved in bacterial quorum sensing.

T581

262568-262743

Epistemic_statement

denotes

By targeting the signal molecules, rather than the bacteria themselves, we believe that resistance is considerably less likely to develop to these antibody-based therapeutics.

T582

263437-263546

Epistemic_statement

denotes

The aim of this study is to examine the interaction between P. aeruginosa PA103 and Acanthamoeba castellanii.

T583

264859-264995

Epistemic_statement

denotes

Furthermore, some limits were observed in the detection of linezolid resistance that prospectively could reduce the therapeutic options.

T584

265078-265363

Epistemic_statement

denotes

In that species, most of the mechanisms involved in the b-lactam resistance are linked to the production of b-lactamases, including clavulanic-acid inhibited expanded-spectrum b-lactamases (ESBLs) and carbapenemases which are the most powerful enzymes able to degradate most b-lactams.

T585

265984-266095

Epistemic_statement

denotes

KPC-2 has been shown to be prevalent in E. coli in Israel and KPC-3 has been reportyed sporadically in the USA.

T586

266717-266867

Epistemic_statement

denotes

Indeed, this determinant has been identified in clinical isolates also harbouring ESBL encoding genes, thus leading to panresistance in those strains.

T587

267347-267534

Epistemic_statement

denotes

Severe sepsis is a serious syndrome with organ failure that may affect a large proportion of the patients admitted to the intensive care unit and whose prediction is often difficult [1] .

T588

267778-267902

Epistemic_statement

denotes

These recommendations were reviewed during the annual meeting of the Society of Critical Care Medicine held in January 2006.

T589

268077-268194

Epistemic_statement

denotes

But, can we monitor therapy for severe sepsis if concepts, tools, ideas and attitudes differ largely between centres?

T590

268195-268395

Epistemic_statement

denotes

With the aim of answering this crucial question, we conducted a survey on the perception of Severe Sepsis, its diagnosis and monitoring through the national network for the Italian Chapter of the SSC.

T591

268797-269086

Epistemic_statement

denotes

On the question whether an educational tool was used to sensitise people to the campaign, 13% of the respondents declared that no specific tool was used and the other 87% (20 centres) stated that they used different educative means (mostly chart documentations and department conferences).

T592

269305-269493

Epistemic_statement

denotes

On the question how data were collected 9 institutions out of 23 (39%) answered that the SSC paper tool or database were used, 11 (47%) a combination of the two, and 3 (23%) other systems.

T593

270073-270205

Epistemic_statement

denotes

One main concept that illustrates the spirit of the SSC is the idea of an early intervention to apply the different recommendations.

T594

270206-270377

Epistemic_statement

denotes

Again, in checking how the time of presentation of sepsis is conceived in the emergency department, in the ward and in the ICU we obtained answers that were quite diverse.

T595

270582-270684

Epistemic_statement

denotes

The remaining 50% had a sort of "a posteriori" diagnosis, losing the possibility of an early approach.

T596

270952-271063

Epistemic_statement

denotes

Surprisingly, in the ICU still 30% of the cases is usually diagnosed through the review of the medical reports.

T597

271577-271710

Epistemic_statement

denotes

In order, to prove that breakpoints for antifungals can be obtained, EUCAST-AFST decided to make a proof of concept with fluconazole.

T598

272162-272341

Epistemic_statement

denotes

Objectives: In recent years K. pneumoniae has been shown to have increasing resistance, due to production of extended-spectrum b-lactamases (ESBLs) or metallo-b-lactamases (MBLs).

T599

272342-272533

Epistemic_statement

denotes

The aim of this study was to record the bacteraemias due to K. pneumoniae in our ICU, to analyse the patterns of resistance, as well as the clinical characteristics of the ensuing infections.

T600

272658-272912

Epistemic_statement

denotes

The demographic characteristics of all patients admitted were recorded, as well as the underlying diseases, disease severity as estimated by the APACHE II score and possible factors predisposing to infections, such as previous consumption of antibiotics.

T601

274229-274488

Epistemic_statement

denotes

Of those who had a carbapenem-sensitive isolate, 35% had been receiving a carbapenem (p = 0.4) Conclusions: Infections due to K. pneumoniae resistant to carbapenems represent a serious clinical problem in our ICU and are associated with a high mortality rate.

T602

274489-274561

Epistemic_statement

denotes

It seems that previous use of carbapenems leads to increased resistance.

T603

274562-274641

Epistemic_statement

denotes

Larger studies are needed in order to obtain statistically significant results.

T604

277110-277258

Epistemic_statement

denotes

Objectives: The role of the multi-gene PE family of proteins unique to mycobacteria, in the pathogenesis of tuberculosis is still poorly understood.

T605

277351-277560

Epistemic_statement

denotes

Our objective was to understand how PE_PGRS33, a surface-exposed protein known to undergo variation among strains, influences TNF-a release from macrophages, and how this is linked to apoptosis of macrophages.

T606

279143-279282

Epistemic_statement

denotes

These results provide the first evidence that variations in the polymorphic repeats of the PGRS domain modulate the innate immune response.

T607

280125-280174

Epistemic_statement

denotes

M. tuberculosis ppk1 could complement the mutant.

T608

280336-280449

Epistemic_statement

denotes

Conclusion: ppk1 likely plays a role in mycobacterial persistence and is a potential target for drug development.

T609

282204-282355

Epistemic_statement

denotes

We studied the cytokine/chemokine profiles associated with LTBI and TB in order to gain insight into ongoing immune activation events in Mtb-infection.

T610

282528-282785

Epistemic_statement

denotes

Interferon-gamma (IFN-g) that was released from sensitised lymphocytes upon ex vivo stimulation with Mtb-specific antigens was determined using the QuantiFERON-TB ® Gold In Tube assay as recommended by the manufacturer (Cellestis Ltd., Carnegie, Australia).

T611

283730-283854

Epistemic_statement

denotes

Assessment of IP-10 might substantially increase the sensitivity of IFN-g release assays (IGRA) for detecting Mtb infection.

T612

284083-284170

Epistemic_statement

denotes

results suggested that all isolates from patients of hospitals I and II were identical.

T613

284432-284528

Epistemic_statement

denotes

Conclusion: One C. difficile strain seems to be predominating in Northern Bavaria CDAD patients.

T614

284669-284863

Epistemic_statement

denotes

Therefore, infection control programmes to restrict spread of C. difficile should not be restricted to hospitals but also should imply other healthcare facilities (nursing homes, house doctors).

T615

285740-285875

Epistemic_statement

denotes

Preliminary results of typing of 14 strains revealed 8 different types with type 001 (21%) and type 015 (14%) as the predominant types.

T616

286168-286321

Epistemic_statement

denotes

Few studies have evaluated risk factors for the development of C. difficile-associated diarrhoea (CDAD) in patients with antibiotic-associated diarrhoea.

T617

286705-286837

Epistemic_statement

denotes

CDAD patients were defined as patients who had diarrhoea and was associated with a positive stool toxin A/B enzyme immunoassay test.

T618

287554-287773

Epistemic_statement

denotes

Conclusions: Our results may help clinicians predict the risk of CDAD in hospitalised patients with antibiotic-associated diarrhoea, guide careful antibiotic prescription and early attention to infection control issues.

T619

288611-288821

Epistemic_statement

denotes

During hospitalisation, 15% VANC cases subsequently received MET, and 12% MET received VANC; 9% MET and 11% VANC received IV MET (unknown if specifically for CDAD), and 1.5% MET and 3.1% VANC received rifampin.

T620

289047-289234

Epistemic_statement

denotes

Despite lower costs of MET vs VANC therapy, total pharmacy costs were similar ($2,439 vs $2,492, p = 0.52), while total hospitalisation costs were higher ($16,953 vs $14,718, p < 0.0001).

T621

289371-289556

Epistemic_statement

denotes

Compared to initial VANC therapy, those treated with MET had higher rates of poor discharge outcomes and greater resource use, however comparisons do not adjust for acute comorbidities.

T622

292011-292284

Epistemic_statement

denotes

Whole-genome multi-strain bacterial microarrays can be used to take a rapid snapshot of gene presence or absence in unsequenced bacterial genomes, and allow large bacterial populations to be interogated for genetic markers of phenotypic, clinical or evolutionary behaviour.

T623

292668-292818

Epistemic_statement

denotes

Surprisingly, about 12% of genes are CV, their presence, absence or variabity can be used to classify an isolate into one of about ten human lineages.

T624

293085-293316

Epistemic_statement

denotes

Since each lineage carries a unique combination of CV genes scattered throughout the chromosome, there was likely to be a common S. aureus ancestor but early evolutionary divergence of lineages, with possible selection in the nose.

T625

293470-293698

Epistemic_statement

denotes

Interestingly, we have been unable to identify any markers that differ between carriage and typical invasive community isolates (not CA-MRSA), suggesting community-acquired invasive disease is strongly dependent on host factors.

T626

293699-293794

Epistemic_statement

denotes

We have also discovered the likely mechanism controlling the independent evolution of lineages.

T627

293795-293982

Epistemic_statement

denotes

A restriction modification pathway found in all S. aureus called Sau1 can block horizontal transfer of DNA between isolates, and the specificity of the system varies according to lineage.

T628

294111-294338

Epistemic_statement

denotes

Not only does this explain independent lineage evolution, but has important implications for how S. aureus continues to evolve, and in particular to acquire MGE leading to increasingly antibiotic resistant and virulent strains.

T629

294339-294422

Epistemic_statement

denotes

S337 Baseline laboratory facilities on remote sites in Africa: too much/too little?

T630

294691-295054

Epistemic_statement

denotes

This requires a pragmatic approach based on a knowledge of the clinically most significant diseases in the area, either due to a high and clinically significant incidence or a high risk of significant morbidity and or mortality due to disease, the outcome of which may require or may benefit from reliable, affordable and readily available laboratory diagnostics.

T631

295257-295801

Epistemic_statement

denotes

In a setting in which a relatively small number of expatriate and national employees are taken care of with limited funding, the healthcare provider needs to be aware of the health risk profile of the region in which the service is rendered, the likely exposure of the population served to the prevalent diseases and the availability of laboratory tests that could or would make a significant difference to clinical disease management if available The main limiting factor in the provision of laboratory support to a medical service is funding.

T632

296107-296281

Epistemic_statement

denotes

The absence of trained laboratory personnel is most often a significant determinant in the decision making process regarding the level of sophistication that can be achieved.

T633

296456-296824

Epistemic_statement

denotes

Long standing main stays of side-room diagnostics such as blood and urine test kits capable of detecting a number of metabolic and other diseases prove to be cost effective, regularly useful, affordable and sustainable whilst sophisticated dry chemistry analysis machines find a very limited application on a remote site with limited medical and other infra-structure.

T634

296825-297054

Epistemic_statement

denotes

Dry chemistry tests that may be useful in this setting are superfluous in a setting in which a patient who requires, e.g., regular kidney function monitoring needs to be evacuated due to the overall limitations beset by the area.

T635

297354-297444

Epistemic_statement

denotes

The effects of those disparities can be observed at both individual and population levels.

T636

297758-297892

Epistemic_statement

denotes

Present and future health challenges related to migration may be more effectively addressed through collaborative global undertakings.

T637

298188-298322

Epistemic_statement

denotes

In the last decade, Southeast Asia has become the epicentre of a number of new disease outbreaks with the potential for global spread.

T638

298483-298609

Epistemic_statement

denotes

In Bangladesh, Nipah virus or one closely related to it has caused several outbreaks in Bangladesh with a high mortality rate.

T639

298770-298871

Epistemic_statement

denotes

Many factors accounting for the emergence of new infections must be in place prior to such outbreaks.

T640

299334-299425

Epistemic_statement

denotes

Surveillance is complicated in the case of a zoonotic disease such as avian influenza H5N1.

T641

299548-299700

Epistemic_statement

denotes

Preventing disease spread in an era of globalisation poses tremendous challenges in developing countries that depend on international trade and tourism.

T642

299836-300012

Epistemic_statement

denotes

Although there are guidelines available for pandemic preparedness as in the case of avian influenza, national plans are totally inadequate and do not measure up to expectation.

T643

300013-300152

Epistemic_statement

denotes

Despite these inadequacies, developing countries in Southeast Asia are making contingency plans in the event of unexpected viral emergence.

T644

300153-300311

Epistemic_statement

denotes

There is no doubt that this will be an uphill battle but certain measures initiated in the region will hopefully reduce the spread of emerging viral diseases.

T645

302116-302264

Epistemic_statement

denotes

FR264205 is an unusual preclinical cephalosporin with promising in vitro activity against Helicobacter pylori and AmpC-hyperproducing P. aeruginosa.

T646

302993-303112

Epistemic_statement

denotes

However, none of these early metabolism inhibitors have proceeded to proof-of-concept therapeutic studies at this time.

T647

304101-304374

Epistemic_statement

denotes

By complementing the screening of diverse, drug-like, infection-friendly compound collections against drugable targets, and early application of structure-based approaches, we should see breakthroughs in the discovery of antibacterial drugs with novel mechanisms of action.

T648

304375-304478

Epistemic_statement

denotes

The natural product approach: advances over the last 10 years that make it an attractive approach again

T649

304479-304712

Epistemic_statement

denotes

There is an urgent medical need to discover and develop new antibiotics, since resistance to antibiotics is becoming an increasingly frequent problem and current development pipelines are lacking innovative, novel antibiotic classes.

T650

305173-305398

Epistemic_statement

denotes

Another reason for their superiority can be explained by the fact that their synthesis evolved naturally in response to needs and challenges of the natural environment generating compounds which are pre-selected for activity.

T651

305399-305499

Epistemic_statement

denotes

Despite these facts, natural product research has recently gone through a phase of reduced interest.

T652

305598-305853

Epistemic_statement

denotes

The reasons for this development may be that natural products are often produced in low quantities and as mixtures of similar compounds, the rediscovery of known compounds and the challenge of natural product derivatisation using classical chemical means.

T653

306304-306458

Epistemic_statement

denotes

The use of modern Genome-based technologies, established in the past few years, offers the opportunity to increase the attractiveness of natural products.

T654

306459-306660

Epistemic_statement

denotes

Genome-based screening technologies provide fast access to the enormous genetic potential of Actinomycetes, soil bacteria known to represent one of the most important sources for bioactive metabolites.

T655

306661-306892

Epistemic_statement

denotes

Additionally, genetic engineering technologies will help to overcome two of the main hurdles connected to natural products, the difficulty in derivatising complex structures and the quantitative improvement of the production yield.

T656

306893-307149

Epistemic_statement

denotes

By focussing on examples in the field of genome based screening and genetic engineering this presentation will give an overview of major improvements that may lead to a rediscovery of natural product based drugs to meet the urgent need for new antibiotics.

T657

307603-307665

Epistemic_statement

denotes

Genotypes and possible sites of recombination were determined.

T658

307880-308003

Epistemic_statement

denotes

However, different phylogenetic relationships among the three clusters were observed in different regions of their genomes.

T659

308330-308843

Epistemic_statement

denotes

Bootscan analysis showed possible recombination between genotypes B and C from nucleotide positions 11500 to 13000, corresponding to the nsp6/nsp7 junction, giving rise to genotype A; and between genotypes A and B from nucleotide positions 21500 to 22500, corresponding to the nsp16/HE junction, giving rise to genotype C. Multiple alignments further narrowed the sites of cross-over to a 143-bp region between nucleotide positions 11750 and 11892, and a 29-bp region between nucleotide positions 21502 and 21530.

T660

309315-309490

Epistemic_statement

denotes

Analysis of a single gene is not sufficient for genotyping of CoV-HKU1, but would require amplification and sequencing of at least two gene loci, one from nsp10 to nsp16 (e.g.

T661

309552-309726

Epistemic_statement

denotes

Influenza activity in temperate regions of Australia typically occurs between May and September, whereas in tropical regions influenza can occur any time throughout the year.

T662

311697-311954

Epistemic_statement

denotes

The results suggest that testing laboratories around Australia and Asia generally utilise accurate and sensitive methods for detection of H5N1, although some laboratories are only testing for Influenza A and are currently not performing specific H5N1 tests.

T663

312073-312206

Epistemic_statement

denotes

Planning public health responses rely on predictive models by which the impact of different intervention strategies can be evaluated.

T664

312207-312366

Epistemic_statement

denotes

Previous research has rather focused on producing predictions for certain localities or under specific conditions and on the administration of antiviral drugs.

T665

312367-312512

Epistemic_statement

denotes

The effectiveness of these interventions depends on various factors which must be explored by sensitivity analyses, based on mathematical models.

T666

312513-312836

Epistemic_statement

denotes

We investigate how pharmaceutical and non-pharmaceutical interventions can mitigate an influenza pandemic and examine how intervention schedules, restricted stockpiles and contact reduction (social distancing measures and partial isolation of cases) determine the course of a pandemic wave and the success of interventions.

T667

313132-313380

Epistemic_statement

denotes

It allows for producing time courses and cumulative numbers of influenza cases, outpatient visits, applied antiviral treatment doses, hospitalisations, deaths and work days lost due to sickness, all of which may be associated with economic aspects.

T668

313381-313612

Epistemic_statement

denotes

Results: The model shows that a timely application of antiviral drugs combined with a quick implementation of contact reduction measures is required to substantially protract the peak of an influenza epidemic and reduce its height.

T669

314220-314335

Epistemic_statement

denotes

When controlling pandemic influenza, pharmaceutical and non-pharmaceutical measures should not be used exclusively.

T670

314336-314449

Epistemic_statement

denotes

Contact reduction measures must be part of mitigation strategies and have the advantage to be not limited per se.

T671

314450-314600

Epistemic_statement

denotes

Objectives: Although influenza (Flu) is an old infectious disease, it will cause pandemics and requires global cooperation for control and prevention.

T672

314755-314847

Epistemic_statement

denotes

However, due to the genetic variability of the influenza it requires vaccination every year.

T673

315504-315684

Epistemic_statement

denotes

Results: Our results indicated that the CF response rates (defined as 4-fold titer increase of the paired sera) for both influenza A and B were low (33.7% and 15.7%, respectively).

T674

315685-315864

Epistemic_statement

denotes

However, the pre-immunised ELISA titers for both influenza A and B were much higher than normal (average 98.3±45.6 RU/mL for Flu A and 176±57.5 RU/mL for Flu B; normal <22 RU/mL).

T675

316032-316123

Epistemic_statement

denotes

However, the rate of pre-immunised sera with protective HI titer (HI 40) was 80.7% (67/83).

T676

316280-316381

Epistemic_statement

denotes

The phenomenon might reflect the quality of the vaccine and the consequences of previous vaccination.

T677

316637-316738

Epistemic_statement

denotes

The appraisal of these AE rates appears to be very important in the decision of HP to get vaccinated.

T678

316739-316866

Epistemic_statement

denotes

A better mediation of the actual very low rates of severe adverse effects may improve the influenza-vaccination rates among HP.

T679

316867-316977

Epistemic_statement

denotes

Objectives: Avian H5N1 influenza viruses could be transmitted to humans, resulting in severe or fatal disease.

T680

317787-317902

Epistemic_statement

denotes

Our data indicate that vaccination may boost cross-subtype cellular and/or humoral immunity against H5N1 influenza.

T681

318112-318264

Epistemic_statement

denotes

No correlation between influenza-specific CD4 T-cells and humoral response was observed, suggesting that this response was mainly CD4 T-cellindependent.

T682

318265-318338

Epistemic_statement

denotes

Differently, CD4 T-cells may help for anti-influenza CD8 T-cell response.

T683

318741-318913

Epistemic_statement

denotes

No correlation between influenza specific CD4 T-cells and humoral responses were observed, suggesting that this type of antibody response was mainly CD4 T-cell independent.

T684

318914-319081

Epistemic_statement

denotes

In this study, we demonstrated that vaccination against seasonal influenza might induce both cellular and humoral cross-reactive immunity against H5N1 avian influenza.

T685

319082-319204

Epistemic_statement

denotes

This cross-type immunity may represent an important component of the immune response against novel influenza A infections.

T686

320653-320792

Epistemic_statement

denotes

Antibody titers and opsonisation titers to 7 serotypes have good correlation in pre-immune sera as well as post-immuue sera in both groups.

T687

321500-321731

Epistemic_statement

denotes

Results: After adjusting for age, invasive status and region, a multivariate logistic regression model showed that non-vaccine (NV) isolates are 1.9 times (1.3−2.7, p = 0.03) more likely to be MR in the post-vaccine release period.

T688

321859-322036

Epistemic_statement

denotes

become more prevalent after introduction of the vaccine), we found that the serotype 19 not F was 4.4 times more likely to expand (2.1−9.1) than other NV serotypes (p < 0.0001).

T689

322037-322180

Epistemic_statement

denotes

A group formed by serotypes [11, 15, 33, 35] is also more likely to increase in prevalence, OR 2.4, 1.3−4.5, p = 0.01) than other NV serotypes.

T690

322276-322620

Epistemic_statement

denotes

Conclusion: Groups of both vaccine and non-vaccine serotypes can be categorised according to their propensity to expand and to acquire MR. Serotype 19F slightly decreases in prevalence but increases in MR rate, while serotype 19 not F both increases in prevalence and acquires resistance at a rate that is proportional to the expansion process.

T691

324420-324658

Epistemic_statement

denotes

The results of this study confirmed the magnitude of the problem of antimicrobial resistance in these low-resource countries and evidenced an alarming increase in the resistance rates to quinolones and to expanded-spectrum cephalosporins.

T692

325511-325708

Epistemic_statement

denotes

(ii) The group of isolates resistant to one group of antibiotics was more likely to be resistant to other antimicrobial groups (under EARSS surveillance) compared to their susceptible counterparts.

T693

325709-326026

Epistemic_statement

denotes

The observation that most resistance is associated with other types of resistance and that the level of associated resistance seems comparable between countries would suggest that the overall reduction of the antibiotic use is probably more important in the society as a whole than targeted reduction of single drugs.

T694

326027-326114

Epistemic_statement

denotes

Our analysis suggest that efforts should be focused on these 'multi' resistant strains.

T695

327176-327342

Epistemic_statement

denotes

In contrast, we were unable to isolate any plasmids from the 3 imipenem-sensitive strains; however, they were positive for the KPC ORF using PCR on total genomic DNA.

T696

327435-327559

Epistemic_statement

denotes

The first cluster of 7 isolates was 86.0% identical suggesting a clonal expansion while the other 5 isolates were unrelated.

T697

327853-327952

Epistemic_statement

denotes

Both a clonal expansion and horizontal plasmid transfer appear to be involved in KPC dissemination.

T698

327953-328207

Epistemic_statement

denotes

In addition, these data suggest that the KPC ORF may reside in the chromosome and is not expressed until the proper inducing agent is present or that the KPC ORF may reside on a transposable element that is not expressed until transferred into a plasmid.

T699

328208-328550

Epistemic_statement

denotes

O362 Pseudomonas aeruginosa resistance rates in association with level of hospital care: data from the EARSS Factors independently associated with increased risk of non-susceptibility to 1 of these agents in P. aeruginosa were intensive care, young age, >48 hours prior hospitalisation, and infections arising from skin/soft tissue and lines.

T700

329023-329153

Epistemic_statement

denotes

DOR MICs were closely related to IPM, on average 2.8 dilutions lower for P. aeruginosa and 0.5 dilutions higher for Acinetobacter.

T701

329435-329616

Epistemic_statement

denotes

S. Corvallis is an uncommon serovar in our experience (0.2% of all isolates) and is remarkable that this serovar represents a high proportion of all qnrS positive isolates detected.

T702

329700-329832

Epistemic_statement

denotes

Orthopaedic and Trauma surgery is an implant specialty where surgical success is related to the insertion of prosthetic joints (e.g.

T703

331103-331275

Epistemic_statement

denotes

The environmental impact of emerging infections is of special concern for endangered wild animal populations, which can be pushed to the brink of extinction by such events.

T704

331276-331439

Epistemic_statement

denotes

Animals, and particularly wild animals, are thought to be the source of more than 70% of all emerging infections ( August to December and also rises in the spring.

T705

331440-331543

Epistemic_statement

denotes

These findings are of importance for the understanding of how influenza virus is perpetuated in nature.

T706

331544-331661

Epistemic_statement

denotes

Of concern is the presence of H5 and H7 subtypes that are prone to change into highly pathogenic variants in poultry.

T707

331798-331941

Epistemic_statement

denotes

This indicates that wild bird surveillance for influenza A virus can be of value as a sentinel system to prevent outbreaks in domestic poultry.

T708

332058-332209

Epistemic_statement

denotes

This fact, in combination with a growing number of humans, creates an arena where domestic animals, humans and finally zoonotic pathogens can interact.

T709

332210-332323

Epistemic_statement

denotes

Influenza A virus is the ultimate actor in this play where some subtypes may change into highly pathogenic forms.

T710

332324-332365

Epistemic_statement

denotes

These may be transmitted directly to man.

T711

332475-332622

Epistemic_statement

denotes

A genetic trait might then readily go from the human to the bird virus so that avian influenza acquires the capacity to pass from person to person.

T712

332623-332733

Epistemic_statement

denotes

With this risk in mind, it would advisable to consider any method to reduce the probability of this happening.

T713

332734-332910

Epistemic_statement

denotes

Contingency planning should take into account the known evolutionary potential of animal viruses and other pathogens to adapt to the environment of humans and domestic animals.

T714

332920-333066

Epistemic_statement

denotes

The use of fluconazole susceptibility profile as a surrogate marker for prediction of voriconazole susceptibility has also been proposed recently.

T715

333372-333506

Epistemic_statement

denotes

Further investigations address the applicability of other methods, which are more practical and/or require shorter incubation periods.

T716

333597-333702

Epistemic_statement

denotes

Utility of flow cytometry for AFST of yeasts and moulds is being currently studied and appears promising.

T717

333965-334096

Epistemic_statement

denotes

Despite these progressions, utility of AFST in direction of antifungal therapy and prediction of clinical outcome is still limited.

T718

334097-334414

Epistemic_statement

denotes

While in vitro triazole (particularly fluconazole) susceptibility results for Candida appear to be optimally correlated with clinical outcome, data are either limited and investigational or fail to demonstrate any significant in vitro-in vivo correlation for most of the remaining fungus-antifungal drug combinations.

T719

334545-334747

Epistemic_statement

denotes

Optimisation of test methodologies and parameters for routine use and expanded in vitro-in vivo correlation studies may further enhance the role of AFST as an adjunct in direction of antifungal therapy.

T720

335298-335554

Epistemic_statement

denotes

The goal of combined molecular and therapeutic interpretation of susceptibility tests is to provide an improved logical basis for decision-making in antibiotic therapy by taking into account the recent progress in the understanding of bacterial resistance.

T721

336025-336144

Epistemic_statement

denotes

In vitro antibiotic susceptibility tests, like other tests in biology, should provide objective quantitative data, e.g.

T722

336151-336267

Epistemic_statement

denotes

For various historical reasons, they also provide subjective interpretation of the data such as clinical categories.

T723

336510-336639

Epistemic_statement

denotes

The best that one can ask of antibiotic susceptibility testing is detection of resistance, in particular of low-level resistance.

T724

336640-336782

Epistemic_statement

denotes

This can be achieved by improved interpretation of the results of in vitro sensitivity tests or by the design of certain genotypic approaches.

T725

336783-337075

Epistemic_statement

denotes

The goal of the proposed approach is to provide the clinician with the necessary results for judicious decision-making in antibiotic therapy utilising available information and to draw his or her attention to the combinations of bacterium and antibiotic for which there is a therapeutic risk.

T726

337649-337737

Epistemic_statement

denotes

However, there are some exceptions, both in Gram-negative and in Gram-positive bacteria.

T727

338029-338122

Epistemic_statement

denotes

However, bactericidal synergism of amikacin with b-lactams or vancomycin is always abolished.

T728

338230-338415

Epistemic_statement

denotes

In this case and several others, interpretive reading of susceptibility tests based on identification of resistance phenotypes may help to identify impaired activity of aminoglycosides.

T729

338416-338550

Epistemic_statement

denotes

Interpretive reading may also allow to identify some pitfalls in the detection of resistance to macrolide and lincosamide antibiotics.

T730

338551-338748

Epistemic_statement

denotes

Staphylococci may be resistant to macrolides by production of a ribosomal methylase encoded by erm genes conferring the MLSB phenotype or by production of an efflux pump encoded by the msr(A) gene.

T731

338749-338837

Epistemic_statement

denotes

In case of inducible MLSB resistance, clindamycin that is not an inducer remains active.

T732

338838-339002

Epistemic_statement

denotes

However, constitutively resistant mutants can be selected by clindamycin and clinical failure during treatment by clindamycin have been reported in a few occasions.

T733

339003-339115

Epistemic_statement

denotes

The use of clindamycin is probably best avoided in severe infections or infections with heavy bacterial inocula.

T734

339303-339447

Epistemic_statement

denotes

By a disk diffusion test, the inducible MLSB phenotype can be identified by the flattening of the clindamycin zone facing the erythromycin disk.

T735

339448-339763

Epistemic_statement

denotes

The relative importance of the contaminated inanimate environment is discussed controversially: Whereas outbreaks due to environmental sources have been described repeatedly, its role as a source for endemic colonisation (and, as a consequence, infection) in intensive care patients has not been firmly established.

T736

339764-340020

Epistemic_statement

denotes

More recent data show that in an ICU, a high figure of 35% of all cases of P. aeruginosa acquisition may originate from contaminated tap water (clonal relationship between isolates) and that retrograde contamination of faucets by patients may occur in 15%.

T737

340021-340156

Epistemic_statement

denotes

However, surveillance of intestinal colonisation (which plays a relevant role in the epidemiology of P. aeruginosa) was not undertaken.

T738

340350-340503

Epistemic_statement

denotes

With regard to infection control, adequate hand hygiene is essential, whereas 'sterilisation' of sinks or routine use of water filters seems impractical.

T739

340504-340657

Epistemic_statement

denotes

Alcohol-based handrubs, via dispensers near the bedside or in coat pockets, should be preferred in most situations over hand washing with soap and water.

T740

340658-340851

Epistemic_statement

denotes

All open water sources including sinks may be a potential habitat of pathogens like P. aeruginosa, and the use of tap water for critically ill or immuno-compromised patients must be restricted.

T741

341337-341504

Epistemic_statement

denotes

Conclusions: Urology sections should be encouraged to monitor the susceptibility of pathogens causing NAUTI in order to tailor a better empirical antibiotic treatment.

T742

341505-341664

Epistemic_statement

denotes

Urologists need to work out guidelines on when to take blood cultures after urological surgery to obtain a more uniform reporting of urosepsis between regions.

T743

341665-341745

Epistemic_statement

denotes

The high prevalence of urosepsis after urological surgery is a cause of concern.

T744

343742-343851

Epistemic_statement

denotes

The emergence of qnr also alerts us to the potential rapid dissemination of quinolone-resistant determinants.

T745

344567-344714

Epistemic_statement

denotes

Urosepsis accounts for approximately 25% of all sepsis cases and may develop from a community or nosocomial acquired urinary tract infection (UTI).

T746

344715-344836

Epistemic_statement

denotes

The underlying UTI is almost exclusively a complicated one with involvement of the parenchymatous urogenital organs (e.g.

T747

344837-344916

Epistemic_statement

denotes

kidneys, prostate) and mostly associated with any kind of obstructive uropathy.

T748

344917-345083

Epistemic_statement

denotes

If urosepsis originates from a nosocomial infection, a broad spectrum of Gram-negative and Gram-positive pathogens have to be expected which are often multiresistant.

T749

345483-345580

Epistemic_statement

denotes

In most cases of urosepsis an early control of the infectious focus is possible and as important.

T750

345658-345990

Epistemic_statement

denotes

Although most antibiotics achieve high urinary concentrations there are several unique properties in complicated UTI, and thus in urosepsis, that influence the activity of the antibiotic substances: (i) The renal pharmacokinetics in unilateral and bilateral renal impairment and in unilateral and bilateral renal obstruction differ.

T751

345991-346062

Epistemic_statement

denotes

(ii) Varations in pH may influence the activity of certain antibiotics.

T752

346063-346262

Epistemic_statement

denotes

(iii) Biofilm infection is frequently found under these conditions, which may increase the minimal inhibitory concentrations (MIC) of the antimicrobials at the site of infection by several 100-folds.

T753

346263-346624

Epistemic_statement

denotes

In order to assess the antibiotic pharmacodynamic properties in such situations not only the MIC as determined in vitro and the plasma concentrations of the free (unbound) drug, which are the guiding principle for many infections, but also the actual renal excretion and the urinary bactericidal activity of an antibiotic substance should be taken into account.

T754

346828-347052

Epistemic_statement

denotes

Since urosepsis originates quite often from catheter associated UTI and after urological interventions, optimal catheter care and optimal strategies to prevent nosocomial UTI may be able to reduce the frequency of urosepsis.

T755

348099-348236

Epistemic_statement

denotes

The risk factors delineated in this study should be considered when selecting initial empirical antibiotic therapy for patients with CAP.

T756

348492-348584

Epistemic_statement

denotes

Persistence or deterioration of CXR abnormalities were not correlated with a poor prognosis.

T757

348585-348798

Epistemic_statement

denotes

Therefore, routine follow-up CXR seems not to be appropriate for patients that respond to therapy and CXR follow-up to exclude a non-infectious cause should not be performed within 4 weeks after initial diagnosis.

T758

348895-348946

Epistemic_statement

denotes

G. Barlow, D. Nathwani, P. Davey (Hull, Dundee, UK)

T759

348947-349116

Epistemic_statement

denotes

Objectives: UK guidelines recommend co-amoxiclav/macrolide or a second/third-generation cephalosporin/macrolide for severe (CURB65 3) community-acquired pneumonia (CAP).

T760

349117-349231

Epistemic_statement

denotes

Observational studies suggest that adherence to guidelines and atypical pathogen cover results in better outcomes.

T761

349232-349312

Epistemic_statement

denotes

There is concern about the ecological impact, however, of broad-spectrum agents.

T762

349798-349889

Epistemic_statement

denotes

The aim of this study was to assess the performance of CURB65 in patients with bacteraemia.

T763

350706-350919

Epistemic_statement

denotes

The most common bacteria were: MSSA (41% of patients), MRSA (23%); various Gram-negatives (16%); thought to be significant coagulasenegative staphylococci (15%); Group A−G streptococci (10%); and enterococci (8%).

T764

351576-351650

Epistemic_statement

denotes

The cut-off for severe illness may need to be lower, however, than in CAP.

T765

351651-351733

Epistemic_statement

denotes

There is the potential, therefore, to identify a low-risk cohort of patients (i.e.

T766

351734-351833

Epistemic_statement

denotes

CURB65 = 0) who may be appropriate for an early switch to oral therapy and discharge from hospital.

T767

351872-351986

Epistemic_statement

denotes

CURB65 2) are more likely to need aggressive therapy according to the principals of the surviving sepsis campaign.

T768

351987-352026

Epistemic_statement

denotes

A large prospective study is warranted.

T769

352551-352684

Epistemic_statement

denotes

This could reflect an evolution of the S. aureus isolates towards a higher virulence and expression of various superantigenic toxins.

T770

352685-352876

Epistemic_statement

denotes

Bacteraemia could partially explain the severity of non-menstrual cases and may be a composite form of shock, frontier between septic shock and STSS, potentially more severe than STSS itself.

T771

354019-354162

Epistemic_statement

denotes

However, both the onset of growth and kill can be delayed and modeled by exponential terms, characterised by time t and dg or dk, respectively.

T772

354359-354504

Epistemic_statement

denotes

Conclusion: The proposed model incorporating five additional terms could account much better for the in vitro situation than a simple Emax-model.

T773

355858-355971

Epistemic_statement

denotes

The intracellular accumulation of AZM and RIF found here corresponds well with what has previously been reported.

T774

355972-356297

Epistemic_statement

denotes

The intracellular accumulation for CXM, DCX and GEN found here, are surprisingly high, since b-lactams are notoriously considered not to accumulate intracellularly, and the 2−4 fold intracellular accumulation of aminoglycosides take several days, but the influx correlates well with the good effect seen in the in vivo model.

T775

358713-359018

Epistemic_statement

denotes

Taking into account the very narrow antibiotherapy choices in these infections, the horizontal transfer of these genes and also the increasing resistance to colistin, the possibility of a further spreading of carbapenemhydrolyzing oxacillinases is of a considerable concern for antimicrobial chemotherapy.

T776

360136-360281

Epistemic_statement

denotes

No class-1 integrons were found that did not have the 3 CS as has been found in several recent blaVIM-2 isolates from diverse geographic regions.

T777

361849-361979

Epistemic_statement

denotes

The significant variability in the bactericidal effect observed, appears to be independent of the isolates' resistance phenotypes.

T778

361980-362225

Epistemic_statement

denotes

Conclusion: Despite the relatively low concentrations used, hbD-3 exhibited bactericidal activity against MBL-producing Pseudomonas aeruginosa nosocomial strains and therefore it would be an attractive alternative to current theurapeutic agents.

T779

362227-362461

Epistemic_statement

denotes

Systems biology is a fast developing research area in life sciences which combines both experimental and theoretical disciplines and which investigates all components of complex biological systems (for example all proteins of a cell).

T780

362610-362850

Epistemic_statement

denotes

It thus allows a holistic view on complex biological systems and to set up improved biological models, particularly if several different experimental parameters are integrated (for example protein interaction and expression profiling data).

T781

362851-363063

Epistemic_statement

denotes

Although Systems biology is usually based on screening assays and thus starts without bias, in contrast to hypothesis-driven research, in most cases it eventually leads to a multitude of novel working hypotheses.

T782

363064-363271

Epistemic_statement

denotes

Particularly interesting are hypotheses derived from bioinformatic concepts like network emergence, robustness and modularity, since it is currently completely unclear if and how they translate into biology.

T783

363272-363465

Epistemic_statement

denotes

Systems biology-based approaches in infectious diseases are even more complex, as they investigate the interactions between the components of two distinct biological systems, pathogen and host.

T784

363757-363975

Epistemic_statement

denotes

By integrating all components of the immune system, Systems biology-based approaches might be able to generate better disease models than previous reductionist approaches focusing on only one or few pathogenic aspects.

T785

364561-364707

Epistemic_statement

denotes

There is growing evidence that genetic variations on both the host and the pathogen side are often crucial for the outcome of infectious diseases.

T786

365243-365743

Epistemic_statement

denotes

However, it will lead to substantial changes in medicine within only a few years, not just because Systems biology-based disease models will considerabley improve our understanding of the pathogenesis and will accelerate and rationalise drug discovery, but also since the ability to determinate individual genetic traits and availability of multi-parameter diagnostics will eventually lead to a much more personalised medicine, in which therapeutical interventions are tailored to single individuals.

T787

366268-366419

Epistemic_statement

denotes

Despite this immense potentiality, only few mutations that are randomly produced during the daily replicative cycles are fixed within the viral genome.

T788

366766-366902

Epistemic_statement

denotes

For this reason, the number of quasispecies is limited if the environment (that is immune and pharmacological pressure) does not change.

T789

367138-367312

Epistemic_statement

denotes

In case of fully suppressive therapy, the virus is unable to generate and/or select new variants, the wild-type strain remains prevalent and the therapy is highly successful.

T790

367313-367544

Epistemic_statement

denotes

By contrast, if therapeutic pressure is inconsistent, erratic, or not sufficiently potent, the virus continues its replicative cycles under drug presence, and this represents the best environment to select mutant-resistant strains.

T791

367545-367758

Epistemic_statement

denotes

The rapidity with which this selection occurs is a function of the genetic barrier of each drug, that in turn is related to the number of mutations occurring to generate a new variant fully resistant to each drug.

T792

367759-367879

Epistemic_statement

denotes

A low genetic barrier means few (1 or 2) mutations are required to generate resistant variants, that will occur rapidly.

T793

370584-370657

Epistemic_statement

denotes

fAUC/MIC appears to best characterise the PD profile of this novel agent.

T794

371114-371220

Epistemic_statement

denotes

Recent studies have shown the enormous potential of the use of phage endolysins as potential therapeutics.

T795

371221-371446

Epistemic_statement

denotes

Objectives: To characterise the staphylococcal phage K-derived protein, LysK, a bifunctional endolysin with antimicrobial activity against MRSA, with a view to identifying the domain or domains responsible for lytic activity.

T796

371856-372045

Epistemic_statement

denotes

SDS-PAGE and zymogram assays were used to visualise the activity of LysK and its deletion derivatives in pQE60 and to assess which domain(s) the lytic activity of LysK could be ascribed to.

T797

372046-372358

Epistemic_statement

denotes

Results: Bioinformatic analysis of LysK (495 amino acids) suggests that it has a modular structure, containing two peptidoglycan hydrolase domains, CHAP (endopeptidase activity) and Amidase_2 (N-acetylmuramoyl-L-alanine amidase activity), at the N-terminus and a cellwall binding domain at the C-terminus (SH3b).

T798

374015-374026

Epistemic_statement

denotes

Our results

T799

374027-374117

Epistemic_statement

denotes

show that in vitro 10 7 bacteria can be reduced to sterility seconds after enzyme contact.

T800

375026-375115

Epistemic_statement

denotes

Resistance to the enzymes has not been found nor do antibodies neutralise their activity.

T801

375116-375288

Epistemic_statement

denotes

Furthermore, a combination of antibiotic and enzyme has been shown to work synergistically resulting in efficient lethal activity in cases of antibiotic resistant bacteria.

T802

375289-375536

Epistemic_statement

denotes

Thus, phage lytic enzymes are a new reagent that may be used in hospitals, nursing homes and the general population to control antibiotic resistant pathogenic bacteria in blood and on mucosal surfaces, offering a capability previously unavailable.

T803

376999-377155

Epistemic_statement

denotes

For these and other reasons two-component signalling systems and their variants have been recognized as targets for the development of anti-infective drugs.

T804

377156-377323

Epistemic_statement

denotes

In this presentation the features of two-component systems that make them potentially attractive targets for the development of novel antiinfectives will be discussed.

T805

377324-377587

Epistemic_statement

denotes

The mechanisms of action and limitations of some classes of previously developed two-component system inhibitors will also be discussed, as will the current and future perspectives for the development of selective inhibitors of these bacterial signalling systems.

T806

377713-377884

Epistemic_statement

denotes

The public have linked the so-called 'superbug' with their experience of dirty hospitals, but the precise role of cleaning in the control of this organism is unknown [1] .

T807

377885-378119

Epistemic_statement

denotes

There is some support for a link between poor hygiene in hospitals and MRSA, since its epidemiological characteristics permit survival in the clinical environment as well as make it potentially vulnerable to the cleaning process [2] .

T808

378270-378365

Epistemic_statement

denotes

Perhaps it is time to introduce microbiological standards for surface levels in hospitals [3] .

T809

378366-378547

Epistemic_statement

denotes

This would not only allay concerns over the grading of hygiene by visual assessment, but would provide a means whereby the removal of dirt becomes an evidence-based science [3, 4] .

T810

378783-379035

Epistemic_statement

denotes

Floors may form a repository for a variety of organisms but they do not play a major role in HAI [5] Pathogens are delivered to patients on hands, and it is more likely that contaminated hand-touch sites are a greater risk for MRSA acquisition [3, 6] .

T811

379036-379197

Epistemic_statement

denotes

Such areas should be prioritised when managing cleaning schedules, since a targeted approach to hospital cleaning might be a useful control factor for MRSA [7] .

T812

379198-379309

Epistemic_statement

denotes

We will never be able to guarantee consistent hand hygiene nor a sustained reduction in antibiotic consumption.

T813

379310-379373

Epistemic_statement

denotes

Improvements in cleaning, however, are not insurmountable [1] .

T814

379374-379467

Epistemic_statement

denotes

More research on the association between MRSA and environmental hygiene is urgently required.

T815

379468-379602

Epistemic_statement

denotes

Basic cleaning could deliver significant cost benefits in MRSA control and could ultimately be our only defence against this organism.

T816

379603-379666

Epistemic_statement

denotes

Carriage of MRSA is most often transient but can be persistent.

T817

379667-379758

Epistemic_statement

denotes

In patients carriage is associated with an increased risk for the development of infection.

T818

379759-379837

Epistemic_statement

denotes

Healthcare workers who carry MRSA may transmit the micro-organism to patients.

T819

379838-379945

Epistemic_statement

denotes

To control transmission and prevent the development of infection, eradication of carriage may be indicated.

T820

379946-380068

Epistemic_statement

denotes

The decision to start decolonisation therapy should be carefully balanced with the risk for the development of resistance.

T821

380069-380271

Epistemic_statement

denotes

Factors that are associated with increased failure rates are: the presence of wounds or other skin lesions, the presence of indwelling devices, multisite carriage and the presence of reservoirs at home.

T822

380611-380712

Epistemic_statement

denotes

Well-designed trials are not available so at present an evidencebased recommendation can not be made.

T823

380713-380807

Epistemic_statement

denotes

The existing data indicate that a combination of two agents including rifampicin is preferred.

T824

380808-380887

Epistemic_statement

denotes

The choice of the agents should be based on the susceptibility testing results.

T825

380888-380973

Epistemic_statement

denotes

Treatment failure may be based on recolonisation from a persisting reservoir at home.

T826

380974-381080

Epistemic_statement

denotes

Therefore, in patients who (repeatedly) fail on decolonisation therapy these sources should be sought for.

T827

381942-382105

Epistemic_statement

denotes

Salmonellosis remained the second most frequent zoonosis with 171,775 reported human cases, despite the fall by 9.5% to an incidence rate of 38.2 compared to 2004.

T828

383150-383273

Epistemic_statement

denotes

Foodborne infections caused by these resistant bacteria pose a particular risk to humans due to possible treatment failure.

T829

383274-383543

Epistemic_statement

denotes

When the results of the routine monitoring of laying-hen flocks are compared to the results from an EU-wide, fully harmonised Salmonella baseline study in laying-hen holdings, the prevalences in the baseline study are remarkably higher than those in routine monitoring.

T830

383544-383748

Epistemic_statement

denotes

This reflects the different sensitivities of sampling scheme and sample types used and demonstrates that a harmonised protocol should be used when comparing the situation in one Member State with another.

T831

384001-384262

Epistemic_statement

denotes

The pathogenicity of these Gram-negative bacteria has been studied intensively during the last decades, resulting in identification and molecular characterisation of a set of chromosomally and extrachromosomally (plasmid pYV) encoded pathogenicity factors (PF).

T832

384263-384370

Epistemic_statement

denotes

Here, the function of the PFs in the context of cell culture and animal infection models will be discussed.

T833

384822-384965

Epistemic_statement

denotes

The Yersinia invasin (Inv) is closely related to the intimins (EaeA) of enteropathogenic (EPEC) and enterohaemorrhagic Escherichia coli (EHEC).

T834

386266-386385

Epistemic_statement

denotes

In the past decades various groups of Escherichia coli associated with diarrhoeal diseases in man have been recognized.

T835

386770-386864

Epistemic_statement

denotes

There are several problems associated with the recognition of these strains in the laboratory.

T836

386865-387020

Epistemic_statement

denotes

Easily detectable phenotypic markers sufficiently specific and sensitive to distinguish these strains from their non-pathogenic counterparts are not known.

T837

387021-387237

Epistemic_statement

denotes

Although certain virulence factors (toxins, adhesins, invasins) are always, or often present in particular groups, the detection of their expression frequently goes beyond the capabilities of diagnostic laboratories.

T838

387439-387578

Epistemic_statement

denotes

Shiga toxin, stx, or intimin, eae) can serve screening purposes but their identification may not prove the actual virulence of the isolate.

T839

387579-387742

Epistemic_statement

denotes

Virulence factors can be shared by members of different pathotypes, and can be present in isolates recovered from healthy individuals or in non-pathogenic strains.

T840

387743-387865

Epistemic_statement

denotes

For some classes it is still not clear which particular combination(s) of these genes are necessary to cause disease (e.g.

T841

388156-388338

Epistemic_statement

denotes

Furthermore, more data on the incidence of these pathotypes should help to understand the role of the individual host's susceptibility in the outcome when encountering these strains.

T842

388792-388965

Epistemic_statement

denotes

In contrast to human medicine in which treatment is customarily directed at the patient, entire groups of animals may be treated with the use of medicated feed and/or water.

T843

388966-389265

Epistemic_statement

denotes

Moreover, growth-promoting dosages are usually at low concentrations for extended time periods, therefore both practices are a potentially significant driving force in accelerating the emergence of resistant bacteria in these animals that can be transferred through contact or food to infect humans.

T844

389266-389507

Epistemic_statement

denotes

The acquisition of quinolone resistance in Gramnegative bacteria is mainly due to chromosomal mutations either in topoisomerase genes (mainly gyrA and parC) or in genes associated with a decreased uptake or by increased efflux of quinolones.

T845

390030-390057

Epistemic_statement

denotes

However, Campylobacter spp.

T846

390058-390212

Epistemic_statement

denotes

easily acquire high levels of FQ resistance associated with a mutation in the gyrA gene, likely because this microorganism does not have topoisomerase IV.

T847

390213-390363

Epistemic_statement

denotes

Several studies have demonstrated an association between FQ use in animals and the subsequent isolation of FQ-resistant bacteria from the same animal.

T848

390364-390521

Epistemic_statement

denotes

Antimicrobial-resistant enteric pathogens can reach humans through direct animal contact, or more commonly, through ingestion of contaminated water or foods.

T849

390522-390755

Epistemic_statement

denotes

Three scenarios may be proposed by which the use of FQ in food animals could affect the treatment of diseases in humans: (1) FQ-resistant bacterial pathogens are selected, and food is contaminated during slaughter and/or preparation.

T850

390756-390963

Epistemic_statement

denotes

After consumption of the food, these pathogens cause an infection that requires antibiotic treatment and therapy is compromised; (2) FQ-resistant bacteria non-pathogenic to humans are selected in the animal.

T851

390964-391298

Epistemic_statement

denotes

When the contaminated food is ingested, the bacteria transfer FQ-resistance determinants, such as plasmid carrying the qnr gene, to other bacteria in the human gut, commensal and potential pathogens; and (3) FQs remain as residue in food products, which allow the selection of antibiotic-resistant bacteria after the food is consumed.

T852

391299-391506

Epistemic_statement

denotes

In conclusion, ongoing surveillance of the antimicrobial susceptibility profiles of foodborne pathogens is needed to identify emerging antimicrobial-resistant phenotypes within the food production continuum.

T853

391507-391642

Epistemic_statement

denotes

Moreover, barriers to stop the dissemination of FQ or other antimicrobial-resistant bacteria from animals to humans should be improved.

T854

391643-391759

Epistemic_statement

denotes

Objectives: It has been suggested that tuberculosis (TB) in the elderly is often atypical and difficult to diagnose.

T855

391760-391831

Epistemic_statement

denotes

There is a lack of information about TB in people over 80 years of age.

T856

391832-391997

Epistemic_statement

denotes

The aim of this study was to examine current clinical manifestations, time to diagnosis and outcomes in old ( 65 years) and in very old ( 80 years) patients with TB.

T857

393598-393679

Epistemic_statement

denotes

Prolonged treatment with isoniazid seems to be safe in anti-TNF treated patients.

T858

394011-394094

Epistemic_statement

denotes

Failed containment results in clinical TB and is associated with proliferating Mtb.

T859

394095-394270

Epistemic_statement

denotes

We thus wondered if in this situation indeterminate or negative QFT-GIT results were associated with positive microscopy, thus serving as a surrogate for the bacterial burden.

T860

395564-395836

Epistemic_statement

denotes

However, the likelihood of having a negative or indeterminate QFT-GIT test result was significantly and independently associated with a positive microscopy (odds ratio [OR] 5.8, 95% CI: 1.2−28.2%; p = 0.03) and with immunesuppression (OR 3.2, 95% CI: 0.91−11.4, p = 0.08).

T861

395837-396002

Epistemic_statement

denotes

Conclusions: To our knowledge this is the first study that demonstrates a significant association of smear-positive TB and negative or indeterminate QFT-GIT results.

T862

396003-396104

Epistemic_statement

denotes

This association was independent of, and stronger than, the effect of concomitant immune-suppression.

T863

396288-396416

Epistemic_statement

denotes

Current WHO guidelines, based on transmission of TB on aeroplane flights, recommend an 8 hour period as a cut off for screening.

T864

396417-396473

Epistemic_statement

denotes

However this was before the routine use of IFN-g assays.

T865

396963-397153

Epistemic_statement

denotes

Presumably due to a lower transmissibility and a well-organised tuberculosis control, transmission of multi-drug resistant tuberculosis (MDR-TB) was so far limited to single secondary cases.

T866

397154-397344

Epistemic_statement

denotes

However, a MDR strain with an unusually low level of rifampicin resistance (MIC 1−2 mg/l) was transmitted from a single source to nine persons, of whom three developed active disease so far.

T867

398279-398568

Epistemic_statement

denotes

Conclusion: The relatively high rate of transmission of this k315/r516 variant may be related to evolutionary development of M. tuberculosis to maintain its transmissibility despite the adaptation to withstand the therapy by our most important anti-mycobacterial drugs; INH and rifampicin.

T868

398569-398676

Epistemic_statement

denotes

More studies are needed to investigate the contribution of k315/r516 MDR strains to transmission of MDR-TB.

T869

398802-398919

Epistemic_statement

denotes

It is considered to introduce the term "intermediate susceptibility" to indicate this level of rifampicin resistance.

T870

400491-400581

Epistemic_statement

denotes

Interestingly, 4 of them showed <1 acid fast bacilli per field on microscopic examination.

T871

400825-401040

Epistemic_statement

denotes

Finally, the 40 remaining smear-negative samples were all found to be negative for IS6110 and RD9, suggesting that the increased sensitivity of the new IS6110-BRD04 probe does not impair the specificity of the test.

T872

401041-401278

Epistemic_statement

denotes

The results obtained for the first evaluation of the new version of the RT-TB kit suggest that the assay is sensitive and specific and may be very promising for the detection of M. tuberculosis in clinical samples containing few bacilli.

T873

401279-401349

Epistemic_statement

denotes

Further experiments are in progress to confirm these preliminary data.

T874

401644-401836

Epistemic_statement

denotes

The present study is a preliminary investigation to assess the suitability of the assay for detection of resistance mutations in rpoB in clinical isolates of M. tuberculosis from Delhi, India.

T875

402770-402945

Epistemic_statement

denotes

It was also interesting to note that 77% of the rifampicin-resistant strains were multidrug resistant, while the corresponding figure for ethambutol-resistant strains was 87%.

T876

403348-403615

Epistemic_statement

denotes

The remaining 28 rifampicin-resistant strains, which hybridised with probe E, may have a mutation at a site other than that complimentary to probe E. Of these, 10 hybridised with probe D, indicating a mutation at the site complimentary to probe D (codons 522 to 527).

T877

404287-404483

Epistemic_statement

denotes

The whole process, from the sample preparation to result analysis, can be completed between 1.5 and 2.5 hours, which greatly shortens the time usually needed for current phenotypic identification.

T878

404922-405150

Epistemic_statement

denotes

Enterotoxigenic B. fragilis (ETBF) have been isolated from various diarrhoeic animal species and epidemiological studies worldwide note a significant correlation between ETBF and human diarrhoeal disease, especially in children.

T879

405151-405349

Epistemic_statement

denotes

The prevalence of ETBF in gastrointestinal diseases in the UK, however, has not been investigated, partly due to the lack of a simple identification test that can be used in diagnostic laboratories.

T880

405350-405575

Epistemic_statement

denotes

The aim of this study was to develop a sensitive and specific multiplex PCR assay for the detection of ETBF directly from faeces, and to investigate if ETBF are associated with cases of community-acquired diarrhoea in the UK.

T881

406557-406702

Epistemic_statement

denotes

A diarrhoeal sample from a 1-yr old male yielded PCR amplimers for both bft-1 and bft-2 suggesting carriage of at least 2 different ETBF strains.

T882

406896-407089

Epistemic_statement

denotes

The distribution of isoforms in the clinical samples was similar to earlier reports from Europe, but the occurrence of 2 different bft isoforms in a faecal sample has not been described before.

T883

407090-407263

Epistemic_statement

denotes

The finding of ETBF in a high proportion (13%) of samples for which there was no other bacterial explanation for the diarrhoea merits further investigation of this pathogen.

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