The effect of a 5-day course of azithromycin on Streptococcus pneumoniae carriage and antimicrobial resistance among Kenyan children discharged from hospital

Background Mass azithromycin distribution reduces child mortality in some settings, potentially through reductions in nasopharyngeal carriage of Streptococcus pneumoniae, but has been associated with increased antimicrobial resistance. Individual-level data are lacking on the impact of azithromycin on antimicrobial resistance over time. Methods We analyzed data from a double-blind, randomized placebo-controlled trial (ClinicalTrials.gov; NCT02414399) which followed 1,398 hospitalized Kenyan children to evaluate the impact of a 5-day course of oral azithromycin at discharge from hospital on pneumococcal carriage and the proportion of isolates (among a random sample) resistant to azithromycin. Randomization to azithromycin or placebo (1:1) was stratified by enrollment county (Kisii or Homa Bay). Using generalized estimating equations, we calculated prevalence ratios (PRs) and 95% confidence intervals for the intervention, adjusting for enrollment site. Results Overall, 1,253/1398 (89.6%) enrolled children received antibiotics during their hospitalization. Pneumococcal carriage at discharge was similar among children randomized to the azithromycin group (158/702 [22.5%]) compared to the placebo group (171/696 [24.6%]; p = 0.4) and did not differ at month 3 (65.6% vs 67.0%; PR:0.98[0.90, 1.06]) or month 6 (66.7% vs 66.5%; PR:1.00[0.92, 1.08]). At discharge, 15.7% of isolates were resistant to azithromycin and there was no difference between azithromycin-treated and placebo groups at month 3 (35/266 [13.2%] vs 32/256 [12.5%]; PR:1.06[0.86, 1.66]) or month 6 (41/245 [16.7%] vs 43/243 [17.6%]; PR:1.01[0.69,1.49]). Conclusions Azithromycin treatment did not effect pneumococcal carriage or antimicrobial resistance 3- or 6-months post-randomization. High inpatient antibiotic use in this recently discharged population may have reduced any further impact of azithromycin.