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

Infection. 2001 Oct;29(5):251-6. doi: 10.1007/s15010-001-1072-3.


Background: 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.

Patients and methods: 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.

Results: 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.

Conclusion: Azithromycin therapy appears to put selective pressure on the infective and native flora of children, promoting the carriage of macrolide-resistant strains.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology*
  • Azithromycin / pharmacokinetics
  • Azithromycin / pharmacology*
  • Child
  • Child, Preschool
  • Drug Resistance, Bacterial*
  • Female
  • Haemophilus influenzae / drug effects
  • Haemophilus influenzae / pathogenicity
  • Half-Life
  • Humans
  • Infant
  • Male
  • Mouth / microbiology
  • Prospective Studies
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / pathogenicity
  • Selection, Genetic


  • Anti-Bacterial Agents
  • Azithromycin