Randomized studies analyzing in human beings the problem of antibiotic resistance are not many. Since the problem was prevalently dealt with in animal studies, some researchers have randomized 224 healthy young adults to receive azithromycin (500 mg/die for three days), clarithromycin (500 mg twice a day for 7 days) or placebo. Pharyngeal bacteria cultures were performed at the beginning of the study, at the end of the treatment and after 14, 28, 42 and 180 days. During therapy, the proportion of saprophyte streptococci resistant to macrolide increased from 26% to 86% with azithromycin and from 30% to 82% with clarithromycin. Between the 14th and the 42nd day, the proportion of these strains progressively decreased, however always remaining significantly high in the azithromycin group. At day 180, the percentage of resistant strains had decreased to 40% and 46% respectively, with azithromycin and clarithromycin; these figures are both however significantly higher than the beginning of the study. In the placebo group, the percentage of resistant streptococci kept practically identical for the whole duration of the follow-up.
The emergence of an antibiotic resistance with new macrolides is dramatically rapid and long-lasting. The authors hypothesized that the greater resistance caused by azithromycin is due to the long action duration, allowing the maintenance in circulation of sub-therapeutical antibiotic doses and so easily evocating resistance.
