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Derm News: 2007.15(4)

Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy volunteers: a randomised, double-blind, placebo-controlled study...

The Lancet 2007;369:482-490
Surbhi Malhotra-Kumar PhD, Christine Lammens BSc, Samuel Coenen MD, Koen Van Herck MD and Prof Herman Goossens
ABSTRACT

Background

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.

Methods

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.

Results

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 500%, 95% CI 417-582; p<00001) and at day 4 in the azithromycin group (534%, 434-635; p<00001). 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 (174% difference, 92-256; p<00001). Use of clarithromycin, but not of azithromycin, selected for the erm(B) gene, which confers high-level macrolide resistance.

Conclusions

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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The Derm News service provided by the Editorial Consultants of Skin Therapy Letter© and its founding editor Dr. Stuart Maddin.