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

Background Group 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. Methods A 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. Results GAS 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). Conclusions Oral 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

Inter-species gene flow drives ongoing evolution of Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis

“…The collection of 501 global SDSE sequences included publicly available short-read sequence data from NCBI sequence read archive (SRA) and complete genome assemblies from NCBI RefSeq until 4 May 2022. These included studies of invasive and non-invasive SDSE from Japan 43 , 48 , 49 , Germany 50 , India 51 , China 52 , Canada 23 , Norway 24 , 34 , 44 , USA 18 , 19 , Denmark 53 , Switzerland 54 and The Gambia 55 . A further 228 invasive and non-invasive isolates were collected from Australia, France, USA, India, Argentina, Trinidad, Japan, Fiji, and Portugal to maximise geographical diversity.…”

Inter-species gene flow drives ongoing evolution ofStreptococcus pyogenesandStreptococcus dysgalactiaesubsp.equisimilis

“…The collection of 501 global SDSE sequences included publicly available short-read sequence data from NCBI sequence read archive (SRA) and complete genome assemblies from NCBI RefSeq until 4 May 2022. These included studies of invasive and non-invasive SDSE from Japan [47][48][49] , Germany 50 , India 51 , China 52 , Canada 23 , Norway 24,34,43 , USA 18,19 , Denmark 53 , Switzerland 54 and The Gambia 55 . A further 228 invasive and non-invasive isolates were collected from Australia, France, USA, India, USA, Argentina, Trinidad, Japan, Fiji, and Portugal to maximise geographical diversity.…”

PeRinatal, neOnatal, and Maternal OuTcomEs with azithromycin prophylaxis in pregnancy and labour (PROMOTE-PROPHYLAXIS): systematic review and meta-analysis

“… 13 , 15 , 16 Instead, there are concerns about infection with azithromycin-resistant bacteria. 17 , 18 Animal studies have shown a link between antenatal azithromycin exposure and development concerns of multiple organ systems in fetus. 19 , 20 Observational studies have shown an association between antenatal azithromycin exposure and increased risk of stillbirth and congenital malformations in infants, raising serious safety concerns.…”