The link between antimicrobial use and increasing resistance is established in an Article in this week’s issue of The Lancet. This information should be a vital warning to physicians of the consequences of inappropriate and uncontrolled antibiotic prescribing.
Resistance to antibiotics is a major public-health problem. Many previous studies have shown a clear relation between antibiotic use and resistance, but they have been limited to showing an association and not a causal effect.
Herman Goossens (University Hospital Antwerp, Belgium) and colleagues did a randomised double-blind placebo-controlled trial with two macrolide antibiotics—clarithromycin and azithromycin*—to investigate the direct effect of antibiotic exposure on resistance in the oral streptococcal flora of healthy volunteers, and the molecular basis for any differences in selection resistance†.
Both drugs significantly increased the proportion of macrolide-resistant streptococci compared with the placebo. However, the proportion of macrolide-resistant streptococci was higher after azithromycin treatment than after clarithromycin use. Azithromycin selected quantitatively more resistant organisms in the early post-therapy phases, whereas clarithromycin qualitatively selected for the erm(B) gene, which confers high-level macrolide resistance. Moreover, the effect of a single course of antibiotics on the naturally occurring non-pathogenic bacteria in the mouth lasted for more than 180 days, which emphasises that such bacteria could serve as a reservoir of resistance for potentially pathogenic bacteria.
The authors conclude: "Macrolide use is the single most important driver of the emergence of macrolide resistance in vivo...[In view of the antibiotic resistance seen here] physicians should take into account the striking ecological side-effects of antibiotics when prescribing such drugs to their patients."
In an accompanying Comment, Stephanie Dancer (Southern General Hospital, Glasgow, UK) states: "The key message is that antibiotic prescribing affects the patient, their environment, and all the people that come into contact with that patient or with their environment. Doctors who understand this point can influence the risk of antimicrobial resistance, not only for our current patients but also for patients in the future."
Professor Herman Goossens, University Hospital Antwerp, Belgium. T) +32 475 327 344
Comment Dr Stephanie Dancer, Southern General Hospital, Glasgow, UK. T) +44 (0)141 201 1705
Journal
The Lancet