Development of Azithromycin Resistance in Streptococcus pneumoniae in the Setting of Trachoma Mass Drug Administration: A Systematic Review

Trachoma is a blinding eye disease caused by the bacterium Chlamydia trachomatis. The current global elimination of trachoma initiative includes the use of mass drug distribution of azithromycin in areas where the prevalence of follicular trachoma is >10% in children aged 1-9 years. This study aims to investigate the high quality evidence of whether mass drug administration for trachoma causes the development of azithromycin resistance in S pneumoniae.  Secondary objectives include (1) changes in the overall S pneumoniae prevalence and (2) concomitant development of non-macrolide resistance. Six databases were searched for articles relevant to the study question. Studies were screened and findings recorded using the PRISMA flow diagram and the Cochrane data collection checklist. Studies were only included if they included both a control and experimental group. Two risk of bias tools were used for quality appraisal of each study. After reviewing all studies, four were included in the final analysis, including one randomized control trial, two cluster-randomized trials and one prospective cohort. Findings showed decreased S pneumoniae prevalence and increased azithromycin resistant isolates following mass drug administration. This review shows that mass drug administration for trachoma can lead to a transient rise in S pneumoniae azithromycin resistance with a possible reduction in overall S pneumoniae prevalence. There is also evidence of macrolide-induced tetracycline and clindamycin resistance. The clinical impact of these findings remains unclear and further studies need to be performed to establish the significance.