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

Isatou Jagne,Saikou Y Bah,Christian Bottomley,Elina Senghore,Abdul Karim Sesay,Abdoulie Bojang,Edrissa Jallow,Umberto D’Alessandro,Anna Roca,Bully Camara,Alexander J Keeley,Claire Oluwalana,Claire E Turner,Thushan I De Silva

doi:10.1186/s12879-022-07080-4

Isatou Jagne, Saikou Y Bah + Show 12 more

Open Access

https://doi.org/10.1186/s12879-022-07080-4

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Abstract

BackgroundGroup A Streptococcus (GAS) is a major human pathogen and an important cause of maternal and neonatal sepsis. Asymptomatic bacterial colonization is considered a necessary step towards sepsis. Intra-partum azithromycin may reduce GAS carriage.MethodsA posthoc analysis of a double-blind, placebo-controlled randomized-trial was performed to determine the impact of 2 g oral dose of intra-partum azithromycin on maternal and neonatal GAS carriage and antibiotic resistance. Following screening, 829 mothers were randomized who delivered 843 babies. GAS was determined by obtaining samples from the maternal and newborn nasopharynx, maternal vaginal tract and breastmilk. Whole Genome Sequencing (WGS) of GAS isolates was performed using the Illumina Miseq platform.ResultsGAS carriage was lower in the nasopharynx of both mothers and babies and breast milk among participants in the azithromycin arm. No differences in GAS carriage were found between groups in the vaginal tract. The occurrence of azithromycin-resistant GAS was similar in both arms, except for a higher prevalence in the vaginal tract among women in the azithromycin arm. WGS revealed all macrolide-resistant vaginal tract isolates from the azithromycin arm were Streptococcus dysgalactiae subspecies equisimilis expressing Lancefield group A carbohydrate (SDSE(A)) harbouring macrolide resistant genes msr(D) and mef(A). Ten of the 45 GAS isolates (22.2%) were SDSE(A).ConclusionsOral intra-partum azithromycin reduced GAS carriage among Gambian mothers and neonates however carriage in the maternal vaginal tract was not affected by the intervention due to azithromycin resistant SDSE(A). SDSE(A) resistance must be closely monitored to fully assess the public health impact of intrapartum azithromycin on GAS.Trial registration ClinicalTrials.gov Identifier NCT01800942

Highlights

Pregnant women and neonates are at high risk of developing sepsis
The trial was conducted at the -Jammeh Foundation for Peace (JFP) hospital, a government-run health facility located in western Gambia that manages approximately 4500 deliveries per year
Post intervention azithromycin reduced Group A Streptococcus (GAS) carriage in the nasopharynx (0.28% versus 1.93%, p = 0.069) and breast milk (0.28% versus 2.48%, p = 0.021) but not in the vaginal tract (1.99% versus 1.93%, p = 1.000) (Table 2)

Summary

Introduction

Pregnant women and neonates are at high risk of developing sepsis. In both groups, the risk persists for several weeks post delivery, and is associated with significant mortality [1, 2]. Staphylococcus aureus and Group B Streptococcus (GBS) are the main causes of maternal and neonatal sepsis [4,5,6]. Group A Streptococcus (GAS; Streptococcus pyogenes) is increasingly recognized as an important Gram-positive pathogen associated with maternal and neonatal sepsis [7,8,9]. Group A Streptococcus (GAS) is a major human pathogen and an important cause of maternal and neonatal sepsis.

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