Impact of intra-partum Azithromycin on carriage of group A streptococcus in The Gambia: a posthoc analysis of a double-blind randomized placebo-controlled trial

Abstract

AbstractBackgroundGroup A Streptococcus (GAS) is a major human pathogen and an important cause of maternal and neonatal sepsis.MethodsWe performed a posthoc analysis of a double-blind, placebo-controlled randomized-trial (ratio 1:1) carried out in The Gambia to determine the impact of one oral dose (2g) of intra-partum azithromycin on maternal and neonatal GAS carriage. Breast milk, nasopharyngeal and vaginal swabs were collected at different time points during 4 weeks post-treatment. All samples were processed using conventional microbiology techniques. Whole genome sequencing (WGS) of GAS isolates was performed by Illumina MiSeq platform.ResultsWe randomized 829 mothers who delivered 843 babies. GAS carriage in mothers in the azithromycin arm was lower in breast milk (0.28% vs 2.48%, Prevalence Ratio (PR)=0.11, 95% CI 0.01-0.90) and the nasopharynx (0.28% vs 1.93%, PR=0.15, 95% CI 0.02-1.19), but not in the vaginal tract (1.99% vs 1.93%, PR=1.03, 95% CI 0.37-2.91). Among neonates, GAS carriage in the nasopharynx was slightly lower in the azithromycin arm (0.57% vs 1.91%, PR=0.30, 95% CI 0.06-1.42). Prevalence of azithromycin-resistant GAS was similar in both arms, except for a higher prevalence in the vaginal tract among women in the azithromycin arm (1.99% vs 0.28%, PR=7.24, 95% CI 0.87-56.92). WGS revealed ten of the 45 GAS isolates (22.2%) were Streptococcus dysgalactiae subspecies equisimilis expressing Lancefield group A carbohydrate (SDSE(A)). All SDSE(A) isolates were azithromycin-resistant, harbouring macrolide resistant genes msrD and mefA.ConclusionsOral intra-partum azithromycin reduced prevalence of GAS carriage among mothers and neonates. Azithromycin-resistant SDSE(A) carriage was observed among participants treated with azithromycin.Short SummaryGroup A streptococcus (GAS) is an important cause of sepsis. One oral dose (2g) of intra-partum azithromycin reduced maternal and neonatal GAS carriage. However, azithromycin-resistant Streptococcus dysgalactiae subspecies equisimilis expressing Lancefield group A carbohydrate was detected in women receiving azithromycin.