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{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/5917310","sourcedb":"PMC","sourceid":"5917310","source_url":"https://www.ncbi.nlm.nih.gov/pmc/5917310","text":"Methods\nWe conducted a multi-centre cross-sectional study. The methodology of the APRES study has been described elsewhere [10,16]. Briefly, we studied the relationship of antibiotic prescription reimbursement data with the results of the samples collected during the APRES study of participants in 27 practices (18 GPs, eight paediatricians and one primary care nurse) from seven different primary healthcare centres in Catalonia in 2010–2011. Clinicians recruited patients aged 4 or more years who did not present any sign of infectious disease and had not taken any antibiotic or had not been admitted to any health centre in the previous 3 months. To obtain samples during the study period from October 2010 to May 2011, individuals were selected at a rate of about 12 patients per week in family medicine or nurse consultations and three patients per week in paediatric care consultations from Monday to Thursday. We did not register patients who declined to participate.\nNasal swabs were collected from all patients according to an established protocol [16,17]. Samples were sent to two different laboratories of the study area: Laboratori Clínic l’Hospitalet and Laboratori Clínic Bon Pastor. All the S. aureus isolated were tested in a central laboratory (Maastricht University Medical Centre, the Netherlands) for susceptibility to 12 antibiotics assumed to represent a range of commonly used antibiotic classes. The procedure included standardised microdilution tests and classification afterwards (resistant versus susceptible) was based on the breakpoints of the minimum inhibitory concentrations (MIC) of S. aureus defined in the 2017 guidelines of the European Committee on Antimicrobial Susceptibility Testing (EUCAST), published by the European Society of Clinical Microbiology and Infectious Diseases, the European Centre for Disease Prevention and Control and the European national breakpoints committees [17] (Table 1). Breakpoints for S. aureus have not changed since 2011. The genotypic structure of the isolated MRSA strains was established with the spa typing method [10].\nTable 1. EUCAST definitions of clinical breakpoints issued by the 2017 European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the number of isolates studied.\n  EUCAST breakpoints* Resistance of the samples collected from the carriers\nAntibiotic S ≤ mg/L R \u003e Mg/L S N (%) R N (%)\nPenicillin 0.125 0.125 99 (12.9) 666 (87.1)\nOxacillin 0.25 2 755 (98.7) 10 (1.3)\nErythromycin 1 2 679 (88.8) 86 (11.2)\nAzithromycin 1 2 676 (88.4) 89 (11.6)\nClindamycin 0.25 0.5 691 (90.3) 74 (9.7)\nCiprofloxacin1 1 1 747 (97.6) 18 (2.4)\nGentamicin 1 1 757 (99.0) 8 (1.0)\nTetracycline 1 2 751 (98.2) 14 (1.8)\nVancomycin 2 2 765 (100) 0 (-)\nLinezolid 4 4 765 (100) 0 (-)\nDaptomycin 1 1 765 (100) 0 (-)\nS = susceptible; R = resistant.\n* The figures correspond to the minimal inhibitory concentrations (MIC) in mg/L above, which germs are considered as resistant.\n1 Breakpoints are based on high dose therapy (750 mg ×2). The boxes of antibiotics reimbursed in the previous 4 years were extracted from the Information System for Research in Primary Care (SIDIAP Database), which contains the computerized primary care medical records of approximately 80% of the Catalan population and data on dispensation of publically financed medication. Despite the availability of the daily defined dose (DDD) of the different antibacterial agents in the same 4-year period, we preferred the use of boxes as suggested by the European Centre for Disease Prevention and Control because of the difficulty of using DDDs for children, invalid for paediatric formulations [18].\n\nStatistical analysis\nDescriptive statistics were used to analyse the individuals’ characteristics and the antibiotic-resistance patterns of the staphylococci isolated. The prevalence of the resistance rates and the number of boxes of the different antibiotics prescribed in the previous 4 years were calculated. To evaluate the association of the previous number of boxes dispensed and the staphylococcal resistance patterns, a multivariate logistic regression analysis model was constructed with resistance of isolated S. aureus strain as the dependent variable and considering age, sex and number of boxes of the different antibiotics prescribed (according to the Anatomical Therapeutic Chemical Classification System) in the prior 4 years as independent variables. Adjusted odds ratios (ORs) with their 95% confidence interval (95% CI) were estimated. Antibiotics evaluated were penicillin, oxacillin, erythromycin, azithromycin, clindamycin, ciprofloxacin, gentamicin, tetracycline, vancomycin, linezolid and daptomycin. Differences were considered to be significant with P \u003c 0.05.\nThe study was approved by the Research Ethics Committee IDIAP Jordi Gol Clinic (P10/55), and each participant voluntarily signed the informed consent. In the case of minors, the father or mother or legal guardian was the one who signed it.\nAnonymity guaranteed and confidentiality, as well as the protection of 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