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

Nazia Khan,Robin Hilder,Barbara Lachana Onen,Robin Bailey

doi:10.3844/ajidsp.2020.109.117

Abstract

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.

Highlights

A blinding eye disease caused by the bacterium Chlamydia trachomatis, causes blindness or visual impairment in an estimated 1.9 million people and is commonly seen in developing areas (WHO, 2018; Trachoma, 2006)
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
This review shows that even when only high quality studies are included, there is still evidence of S pneumoniae resistance to azithromycin in the setting of mass drug administration for trachoma

Summary

Introduction

A blinding eye disease caused by the bacterium Chlamydia trachomatis, causes blindness or visual impairment in an estimated 1.9 million people and is commonly seen in developing areas (WHO, 2018; Trachoma, 2006). Infection by C trachomatis serotypes A, B, or C results in prolonged conjunctival inflammation causing mucopurulent keratoconjunctivitis (Mohammadpour et al, 2016). The infection causes destruction of normal conjunctival epithelium resulting in replacement of subepithelial stroma with type IV and V collagen (Whittum-Hudson et al, 1986). Recurrent infections over several years can lead to extensive eyelid scarring and subsequently trichiasis, or inversion of eyelashes, which can rub against the eyeball and cause corneal scarring. This can progress to irreversible opacities, visual impairment and blindness (WHO, 2018). This progression of the disease can be graded based on the World Health Organization’s (WHO)

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