Article

Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy volunteers

Department of Medical Microbiology, University of Antwerp, Belgium.
The Lancet (Impact Factor: 45.22). 03/2007; 369(9560):482-90. DOI: 10.1016/S0140-6736(07)60235-9
Source: PubMed

ABSTRACT Resistance to antibiotics is a major public-health problem, and studies that link antibiotic use and resistance have shown an association but not a causal effect. We used the macrolides azithromycin and clarithromycin to investigate the direct effect of antibiotic exposure on resistance in the oral streptococcal flora of healthy volunteers.
Volunteers were treated with azithromycin (n=74), clarithromycin (74), or placebo (76) in a randomised, double-blind trial. Pharyngeal swabs were obtained before and after administration of study treatment through 180 days. The proportion of streptococci that were macrolide resistant was assessed and the molecular basis of any change in resistance investigated. Analyses were done on an intent-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT00354952.
The number of dropouts (n=20) was much the same in all groups until day 42; dropouts increased substantially at day 180 (105). Both macrolides significantly increased the proportion of macrolide-resistant streptococci compared with the placebo at all points studied, peaking at day 8 in the clarithromycin group (mean increase 50.0%, 95% CI 41.7-58.2; p<0.0001) and at day 4 in the azithromycin group (53.4%, 43.4-63.5; p<0.0001). The proportion of macrolide-resistant streptococci was higher after azithromycin treatment than after clarithromycin use, with the largest difference between the two groups at day 28 (17.4% difference, 9.2-25.6; p<0.0001). Use of clarithromycin, but not of azithromycin, selected for the erm(B) gene, which confers high-level macrolide resistance.
This study shows that, notwithstanding the different outcomes of resistance selection, macrolide use is the single most important driver of the emergence of macrolide resistance in vivo. Physicians prescribing antibiotics should take into account the striking ecological side-effects of such antibiotics.

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    • "More than 60 years ago, the introduction of penicillin played a decisive role in the treatment of infectious diseases [1]. Over the decades, antibiotic (ATB) overuse and misuse have unfortunately led to an increased rate of adverse side effects, a higher cost of treatment and a higher rate of antimicrobial resistance to community pathogens, a phenomenon which is now a worldwide public health problem [2]. In fact, the World Health Organization (WHO) selected combating antimicrobial resistance as the theme for World Health Day 2011[3]. "
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    ABSTRACT: Introduction Indiscriminate use of antibiotics contributes to a global spread of antimicrobial resistance. Previous studies showed an excessive consumption of antibiotics purchased without medical prescription from community pharmacies, mainly in developing countries. There is a shortage of studies revealing the role of community pharmacists in the overuse of antibiotics. Our objective is to study the dispensing policy of non-medical prescription antibiotics in community pharmacies, assessing the possible influence of the socio-economic level of the area over this practice. Methods A cross-sectional study was conducted between February and May 2011 among 100 pharmacists working in Beirut's pharmacies and its suburbs. Pharmacies were divided into 2 groups according to the socio-economic level of the population living in the pharmacy area. A self-administered questionnaire was filled by pharmacists. Results Over-the-counter antibiotic availability existed in both higher and lower socio-economic areas: on the whole, 32% of antibiotics were dispensed without medical prescription, with higher frequency in lower socio-economic areas (p = 0.003). Dispensing injectable antibiotics without medical prescription was significantly higher in lower socio-economic areas (p = 0.021), as well as dispensing an association of 2 antibiotics without medical prescription (p = 0.001). Pharmacists working in lower socio-economic areas recommended more frequent antibiotics to children and the elderly (p < 0.001 and p = 0.004, respectively). Conclusion Dispensing antibiotics without medical prescription in Beirut community pharmacies is a common practice, particularly in lower socioeconomic areas. This public health problem should be addressed at the social, educational, and legislative levels.
    Journal of Infection and Public Health 08/2014; 8(1). DOI:10.1016/j.jiph.2014.07.003
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    • "More than 60 years ago, the introduction of penicillin played a decisive role in the treatment of infectious diseases [1]. Over the decades, antibiotic (ATB) overuse and misuse have unfortunately led to an increased rate of adverse side effects, a higher cost of treatment and a higher rate of antimicrobial resistance to community pathogens, a phenomenon which is now a worldwide public health problem [2]. In fact, the World Health Organization (WHO) selected combating antimicrobial resistance as the theme for World Health Day 2011[3]. "
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    ABSTRACT: Background: Indiscriminate use of antibiotics contributes to the spread of antimicrobial resistance globally. Observations showed an excessive consumption of antibiotics purchased without prescriptions from community pharmacies in many countries all over the world. Studies denoting the role of community pharmacists in the overuse of antibiotics lack on the international and Lebanese levels. Objective: Our objective was to describe over-the-counter availability of antibiotics in community pharmacies, insisting on the influence of the socio-economic level of the area on this practice. Setting: Pharmacies in Beirut and its suburbs. Method: Between February and May 2011, we conducted a cross-sectional study. One hundred pharmacists completed a self-administered questionnaire. They were stratified into 2 groups: those working in high versus low socio-economic areas. Main outcome measure: the relation between the socio-economic level of the area and the amount and characteristics of dispensing antibiotic without prescription by community pharmacists. Results: Over-the-counter antibiotic availability existed in both socio-economic areas: overall 32% of the antibiotics delivered by pharmacists were dispensed without medical prescription, with higher frequency in low socio-economic regions (36.73% ±18.12 versus 26.74 ± 13.87) (p= 0.003). The prescription of injectable antibiotics was significantly higher in low socio-economic areas (29% versus 10%, p=0.021), as well as the prescription of 2 antibiotics at the same time (30.7% versus 4.2%, p=0.001). Pharmacists working in low socio-economic areas recommended more frequently antibiotics to children and elderly, compared to those working in high socio-economic areas (respectively 69.2% versus 27.1%, p< 0.001 and 48% versus 21%, p=0.004). In low socio-economic regions, pharmacists prescribed more frequently antibiotics for cases of bloody diarrhea or burning with urination. Conclusion: The amount of antibiotic delivery without prescription in Beirut community pharmacies is high, particularly in low socioeconomic regions. This public health problem should be solved at the social, educational, and legislative levels.
    Journal of Infection and Public Health 07/2014;
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    • "In particular high use of clarithromycin and azithromycin in the Emilia Romagna region appears unjustified, since international guidelines do not recommended these agents as first-line treatment of common childhood infections [29-32]. Furthermore, longer plasma half-life of azithromycin and clarithromycin in contrast to erythromycin might even accelerate the emergence of antibiotic resistance [33,34]. "
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    ABSTRACT: Background To describe the utilisation of antibiotics in children and adolescents across 5 European countries based on the same drug utilisation measures and age groups. Special attention was given to age-group-specific distributions of antibiotic subgroups, since comparison in this regard between countries is lacking so far. Methods Outpatient paediatric prescriptions of systemic antibiotics during the years 2005-2008 were analysed using health care databases from the UK, the Netherlands, Denmark, Italy and Germany. Annual antibiotic prescription rates per 1,000 person years were estimated for each database and stratified by age (≤4, 5-9, 10-14, 15-18 years). Age-group-specific distributions of antibiotic subgroups were calculated for 2008. Results With 957 prescriptions per 1000 person years, the highest annual prescription rate in the year 2008 was found in the Italian region Emilia Romagna followed by Germany (561), the UK (555), Denmark (481) and the Netherlands (294). Seasonal peaks during winter months were most pronounced in countries with high utilisation. Age-group-specific use varied substantially between countries with regard to total prescribing and distributions of antibiotic subgroups. However, prescription rates were highest among children in the age group ≤4 years in all countries, predominantly due to high use of broad spectrum penicillins. Conclusions Strong increases of antibiotic prescriptions in winter months in high utilising countries most likely result from frequent antibiotic treatment of mostly viral infections. This and strong variations of overall and age-group-specific distributions of antibiotic subgroups across countries, suggests that antibiotics are inappropriately used to a large extent.
    BMC Pediatrics 07/2014; 14(1):174. DOI:10.1186/1471-2431-14-174 · 1.92 Impact Factor
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