Influence of macrolide antibiotics on promotion of resistance in the oral flora of children

The long elimination half-life of azithromycin allows subinhibitory serum and epithelial lining fluid (ELF) concentrations over a period of several weeks post treatment, which may have an impact on the emergence of macrolide resistance. In this prospective, open-label, randomized study, four macrolides and the azalide azithromycin were studied for their likelihood to promote resistance in the oral flora of children with respiratory tract infections. Children were randomly assigned to receive azithromycin, clarithromycin, erythromycin, roxithromycin and josamycin. Throat swabs were obtained prior to treatment and weekly for 6 weeks. Minimum inhibitory concentrations (MICs) for resistant strains were assessed by E-test and National Committee for Clinical laboratory Standards (NCClS) broth microdilution. One week post treatment, up to 90% of children harbored macrolide-resistant strains in their oral flora. Except for azithromycin, the percentage of patients colonized by resistant organisms decreased to a rate of 17% for clarithromycin (10/60), erythromycin (2/12) and josamycin (2/12) and 33% for roxithromycin (4/12) after 6 weeks. In the azithromycin group, 85% (51/60) of patients were colonized by macrolide-resistant organisms after 6 weeks, 11.6% (7/60) of children suffered from reinfection. Azithromycin therapy appears to put selective pressure on the infective and native flora of children, promoting the carriage of macrolide-resistant strains.