PMC:5917310 / 13365-19742
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/5917310","sourcedb":"PMC","sourceid":"5917310","source_url":"https://www.ncbi.nlm.nih.gov/pmc/5917310","text":"Discussion\n\nMain findings\nWe found an average S. aureus nasal colonization rate of 19.3%. Except for the known high resistance against penicillin, the highest recorded resistance rate was found for azithromycin, and a total of 10 MRSA strains were isolated (1.3%). Despite not observing statistically significant differences, a trend towards a relationship between the dispensation of antibiotics in the previous 4 years and the isolation of resistant microorganisms in otherwise healthy carriers was observed in this study. However, a significant association was found between previous number of packages of penicillin dispensed and penicillin-resistant strains of S. aureus.\n\nLimitations and strengths\nThere are a number of limitations to this study. Although the most important limitation of this study was that the fieldwork was conducted in 2010 and 2011, we used the current resistance breakpoints published in 2017. We do not think the results would have been different if the samples had been collected more recently, since the consumption of antibiotics in our country has been stable over the last years and the main aim of the present study was to determine a possible relationship between previous antibiotic exposure and the prevalence of relevant resistant strains in the noses of healthy individuals. On the other hand, since we carried out a cross-sectional study and compared the results of the resistance patterns of the staphylococci harboured with previous antibiotic exposure, we cannot infer any causality effect between antibiotic exposure and resistance. However, we were able to compare the number of boxes of antibiotics previously dispensed and the resistance patterns of commensal staphylococci in otherwise healthy individuals.\nAnother limitation of the study is the fact that we considered antibiotics dispensed in the previous 4 years. Prescription of antibiotics based on reimbursement data can mimic antibiotic consumption in most European countries, but is not true in southern European countries. A landmark paper published in 2007 with the use of sales data in 2002–2005 showed a difference between prescription and consumption of up to 30% in Spain, mainly due to the over-the-counter sale of antibiotics without a medical prescription and antibiotics prescribed by the private sector [19]. A higher antibiotic consumption would very likely have been associated with greater resistance rates to antibiotics.\nAnother weakness is that this study monitors colonisation at a single time-point, although colonisation is known to be variable over time and it should be differentiated between persistent and intermitted carriers [20]. Only nasal swab samples were used to determine S. aureus colonization status, as the study protocol did not include swabbing of extranasal body sites. While the prevalence might be underestimated by using nasal swabs, we assume our final sample of S. aureus to be representative of all carriage. We also assume that antimicrobial resistance patterns in the commensal flora of the nose are comparable with isolates of pathogenic staphylococci. However, for purposes of empirical treatment, data on resistance of pathogenic strains would also be required.\nThe greatest strength of this work is that it is a study in primary care patients. We are therefore able to extrapolate these results to what we observe in primary care.\n\nComparison with other studies\n\nS. aureus and MRSA carriers\nWe found an average S. aureus nasal colonization rate of 19.3%, which is comparable to previously described colonization rates in the general population in Europe and the United States [21,22]. The low prevalence of MRSA isolates, 10 (1.3%) was also found to be consistent with studies from Europe. We observed a positive association between previous dispensation of any antibiotics and isolation of MRSA, but caution is needed as MRSA was only isolated in 1.3% of the individuals in our study. This is consistent with previous hospital studies where antibiotic surgical prophylaxis increases nasal carriage of antibiotic-resistant staphylococci [23]. Evidence seems to indicate that the endogenous microflora of the patient may be critical since clinical studies have found that S. aureus skin colonisation increases the risk of a subsequent infection by three-fold, and up to 80% of cases of staphylococcal bacteraemia are caused by strains identical to those in the patient’s nasal cavity [24]. Furthermore, patient colonisation with S. aureus is associated with a 2–9-fold increased risk of infection [25].\n\nAntibiotic consumption and antibiotic-resistant association\nThe association between antibiotic consumption and antibiotic-resistant organisms has been widely observed, mainly for other respiratory tract pathogens. For instance, Granizo et al. observed a clear association between previous use of macrolides and β-lactam with erythromycin-resistant pneumococci in Spain [26]. Also, Malotra et al. note that azithromycin and erythromycin use increases resistance of streptococci in healthy carriers [27]. We already knew of the relationship between antibiotic prescribing and bacterial resistance in primary care when antibiotics were prescribed for respiratory or urinary infection [2]. Other studies have also shown an association between previous consumption of antibiotics and S. aureus resistance. For example, in a recent randomised controlled trial, Australian children diagnosed with bronchiectasis assigned to intermittent azithromycin consumption showed higher macrolide-resistant S. aureus carriage than those assigned to placebo [28].\nThe commensal flora of community-dwelling persons is, therefore, becoming an important reservoir of resistant bacteria. Fighting antibiotic resistance starts with the restricted use of antibiotics, leading to less selection pressure on the bacterial flora circulating in the population, but also on the commensal flora in an individual. Knowledge of the local resistance rates of the most common organisms to antibiotics is crucial for better prescribing of antibiotics. In a recent paper from the APRES project, van Bijnen et al. observed that many guidelines for skin infections do not contain data on local resistance [29]. GPs should be informed of the resistance profiles of the most frequent organisms causing infectious disease for more prudent use of 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