Mass distribution of azithromycin for trachoma control is associated with increased risk of azithromycin-resistant Streptococcus pneumoniae carriage in young children 6 months after treatment

Clin Infect Dis. 2013 Jun;56(11):1519-26. doi: 10.1093/cid/cit137. Epub 2013 Mar 13.

Abstract

Background: Emerging evidence suggests that the mass distribution of azithromycin for trachoma control (MDA) may increase circulation of macrolide resistance in bacteria associated with severe pediatric infections in treated communities.

Methods: We examined the effect of MDA on nasopharyngeal carriage of antibiotic-resistant Streptococcus pneumoniae among 1015 young children living in rural Tanzania. MDA with a single dose of oral azithromycin was provided in 4 of 8 communities where trachoma prevalence was ≥10%. Isolates were tested for susceptibility to azithromycin (AZM) and commonly used antibiotics by disk diffusion and Etest. We calculated the proportion of antibiotic-resistant S. pneumoniae carriage at baseline and again 1, 3, and 6 months after treatment, and at comparable intervals in the untreated villages.

Results: The proportion of AZM-resistant isolates was similar between groups at baseline (MDA: 35.8% vs non-MDA: 35.4%), however, this proportion was greater in the MDA group in all subsequent surveys. At 6 months, the percentage of AZM-resistant isolates was significantly higher in the MDA group (81.9% vs 46.9%, P < .001). The odds of AZM-resistant carriage was 5-fold greater in the MDA group (odds ratio, 4.95 [95% confidence interval, 3.23-7.61]). The proportion of isolates clinically resistant to AZM (minimum inhibitory concentration ≥16 µg/mL) was also significantly greater in the MDA group at 6 months (35.3% vs 12.4%, P < .006).

Conclusions: Mass distribution of a single dose of oral azithromycin for trachoma was associated with increased circulation of macrolide-resistant S. pneumoniae carriage among young children in the 6 months following treatment. It is crucial that changes in antibiotic resistance patterns and their clinical significance in the treatment of severe pediatric infections be assessed in future MDA trials.

Keywords: S. pneumoniae; antimicrobial resistance; azithromycin; children; trachoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / adverse effects
  • Azithromycin / administration & dosage*
  • Azithromycin / adverse effects
  • Carrier State / epidemiology
  • Carrier State / microbiology*
  • Child, Preschool
  • Cohort Studies
  • Drug Resistance, Bacterial
  • Female
  • Humans
  • Infant
  • Male
  • Microbial Sensitivity Tests
  • Pneumococcal Infections / epidemiology
  • Pneumococcal Infections / microbiology*
  • Prevalence
  • Risk Factors
  • Streptococcus pneumoniae / drug effects
  • Streptococcus pneumoniae / isolation & purification
  • Tanzania / epidemiology
  • Trachoma / drug therapy*
  • Trachoma / epidemiology

Substances

  • Anti-Bacterial Agents
  • Azithromycin