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Published in: BMC Infectious Diseases 1/2022

Open Access 01-12-2022 | Streptococci | Research

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

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

Published in: BMC Infectious Diseases | Issue 1/2022

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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
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Literature
2.
go back to reference Say L, et al. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health. 2014;2(6):e323–33.CrossRef Say L, et al. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health. 2014;2(6):e323–33.CrossRef
3.
go back to reference Seale AC, et al. Maternal and early onset neonatal bacterial sepsis: burden and strategies for prevention in sub-Saharan Africa. Lancet Infect Dis. 2009;9(7):428–38.CrossRef Seale AC, et al. Maternal and early onset neonatal bacterial sepsis: burden and strategies for prevention in sub-Saharan Africa. Lancet Infect Dis. 2009;9(7):428–38.CrossRef
4.
go back to reference Knowles SJ, et al. Maternal sepsis incidence, aetiology and outcome for mother and fetus: a prospective study. BJOG. 2015;122(5):663–71.CrossRef Knowles SJ, et al. Maternal sepsis incidence, aetiology and outcome for mother and fetus: a prospective study. BJOG. 2015;122(5):663–71.CrossRef
5.
go back to reference Simonsen KA, et al. Early-onset neonatal sepsis. Clin Microbiol Rev. 2014;27(1):21–47.CrossRef Simonsen KA, et al. Early-onset neonatal sepsis. Clin Microbiol Rev. 2014;27(1):21–47.CrossRef
6.
go back to reference Okomo U, et al. Aetiology of invasive bacterial infection and antimicrobial resistance in neonates in sub-Saharan Africa: a systematic review and meta-analysis in line with the STROBE-NI reporting guidelines. Lancet Infect Dis. 2019;19(11):1219–34.CrossRef Okomo U, et al. Aetiology of invasive bacterial infection and antimicrobial resistance in neonates in sub-Saharan Africa: a systematic review and meta-analysis in line with the STROBE-NI reporting guidelines. Lancet Infect Dis. 2019;19(11):1219–34.CrossRef
7.
go back to reference Ekelund K, et al. Invasive group A, B, C and G streptococcal infections in Denmark 1999–2002: epidemiological and clinical aspects. Clin Microbiol Infect. 2005;11(7):569–76.CrossRef Ekelund K, et al. Invasive group A, B, C and G streptococcal infections in Denmark 1999–2002: epidemiological and clinical aspects. Clin Microbiol Infect. 2005;11(7):569–76.CrossRef
8.
go back to reference Rantala S, et al. Clinical presentations and epidemiology of beta-haemolytic streptococcal bacteraemia: a population-based study. Clin Microbiol Infect. 2009;15(3):286–8.CrossRef Rantala S, et al. Clinical presentations and epidemiology of beta-haemolytic streptococcal bacteraemia: a population-based study. Clin Microbiol Infect. 2009;15(3):286–8.CrossRef
9.
go back to reference Anderson BL. Puerperal group A streptococcal infection: beyond Semmelweis. Obstet Gynecol. 2014;123(4):874–82.CrossRef Anderson BL. Puerperal group A streptococcal infection: beyond Semmelweis. Obstet Gynecol. 2014;123(4):874–82.CrossRef
10.
go back to reference Ronchetti MP, et al. Neonatal Sepsis. Arch Paediatrics Dev Pathol. 2017;1(3):1015. Ronchetti MP, et al. Neonatal Sepsis. Arch Paediatrics Dev Pathol. 2017;1(3):1015.
11.
go back to reference Revelas A, Taxmazidis O. Group A streptococcal infections in children. Southern Afr J Epidemiol Infect. 2015;27(3):98–103.CrossRef Revelas A, Taxmazidis O. Group A streptococcal infections in children. Southern Afr J Epidemiol Infect. 2015;27(3):98–103.CrossRef
12.
go back to reference Barth D, et al. Invasive and non-invasive group A β-haemolytic streptococcal infections in patients attending public sector facilities in South Africa: 2003–2015. South Afr J Infect Dis. 2017;33(1):12–7. Barth D, et al. Invasive and non-invasive group A β-haemolytic streptococcal infections in patients attending public sector facilities in South Africa: 2003–2015. South Afr J Infect Dis. 2017;33(1):12–7.
13.
go back to reference Belard S, et al. beta-Hemolytic streptococcal throat carriage and tonsillopharyngitis: a cross-sectional prevalence study in Gabon Central Africa. Infection. 2015;43(2):177–83.CrossRef Belard S, et al. beta-Hemolytic streptococcal throat carriage and tonsillopharyngitis: a cross-sectional prevalence study in Gabon Central Africa. Infection. 2015;43(2):177–83.CrossRef
14.
go back to reference Armitage EP, et al. High burden and seasonal variation of paediatric scabies and pyoderma prevalence in The Gambia: a cross-sectional study. PLoS Negl Trop Dis. 2019;13(10):e0007801.CrossRef Armitage EP, et al. High burden and seasonal variation of paediatric scabies and pyoderma prevalence in The Gambia: a cross-sectional study. PLoS Negl Trop Dis. 2019;13(10):e0007801.CrossRef
15.
go back to reference Chuang I, et al. Population-based surveillance for postpartum invasive group a streptococcus infections, 1995–2000. Clin Infect Dis. 2002;35(6):665–70.CrossRef Chuang I, et al. Population-based surveillance for postpartum invasive group a streptococcus infections, 1995–2000. Clin Infect Dis. 2002;35(6):665–70.CrossRef
16.
go back to reference Leonard A, et al. Severe group A streptococcal infections in mothers and their newborns in London and the South East, 2010–2016: assessment of risk and audit of public health management. BJOG. 2019;126(1):44–53.CrossRef Leonard A, et al. Severe group A streptococcal infections in mothers and their newborns in London and the South East, 2010–2016: assessment of risk and audit of public health management. BJOG. 2019;126(1):44–53.CrossRef
17.
go back to reference Barth DD, et al. Rationale and design of the African group A streptococcal infection registry: the AFROStrep study. BMJ Open. 2016;6(2):e010248.CrossRef Barth DD, et al. Rationale and design of the African group A streptococcal infection registry: the AFROStrep study. BMJ Open. 2016;6(2):e010248.CrossRef
18.
go back to reference Seale AC, et al. Invasive Group A Streptococcus Infection among Children, Rural Kenya. Emerg Infect Dis. 2016;22(2):224–32.CrossRef Seale AC, et al. Invasive Group A Streptococcus Infection among Children, Rural Kenya. Emerg Infect Dis. 2016;22(2):224–32.CrossRef
19.
go back to reference Martin J. The Streptococcus pyogenes Carrier State, in Streptococcus pyogenes: Basic Biology to Clinical Manifestations. In: Ferretti JJ, Stevens DL, Fischetti VA, editors. University of Oklahoma Health Sciences Center. 2016. Martin J. The Streptococcus pyogenes Carrier State, in Streptococcus pyogenes: Basic Biology to Clinical Manifestations. In: Ferretti JJ, Stevens DL, Fischetti VA, editors. University of Oklahoma Health Sciences Center. 2016.
20.
go back to reference Efstratiou ALT. Streptococcus pyogenes: basic biology to clinical manifestations. In: Ferretti JJ, Stevens DL, Fischetti VA, editors. University of Oklahoma Health Sciences Center. 2016. Efstratiou ALT. Streptococcus pyogenes: basic biology to clinical manifestations. In: Ferretti JJ, Stevens DL, Fischetti VA, editors. University of Oklahoma Health Sciences Center. 2016.
21.
go back to reference Roca A, et al. Oral azithromycin given during labour decreases bacterial carriage in the mothers and their offspring: a double-blind randomized trial. Clin Microbiol Infect. 2016;22(6):565 e1-9.CrossRef Roca A, et al. Oral azithromycin given during labour decreases bacterial carriage in the mothers and their offspring: a double-blind randomized trial. Clin Microbiol Infect. 2016;22(6):565 e1-9.CrossRef
22.
go back to reference Roca A, et al. Prevention of bacterial infections in the newborn by pre-delivery administration of azithromycin: Study protocol of a randomized efficacy trial. BMC Pregnancy Childbirth. 2015;15:302.CrossRef Roca A, et al. Prevention of bacterial infections in the newborn by pre-delivery administration of azithromycin: Study protocol of a randomized efficacy trial. BMC Pregnancy Childbirth. 2015;15:302.CrossRef
23.
go back to reference Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30(15):2114–20.CrossRef Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30(15):2114–20.CrossRef
24.
go back to reference Bankevich A, et al. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol. 2012;19(5):455–77.CrossRef Bankevich A, et al. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol. 2012;19(5):455–77.CrossRef
25.
go back to reference Gurevich A, et al. QUAST: quality assessment tool for genome assemblies. Bioinformatics. 2013;29(8):1072–5.CrossRef Gurevich A, et al. QUAST: quality assessment tool for genome assemblies. Bioinformatics. 2013;29(8):1072–5.CrossRef
26.
go back to reference Stamatakis A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics (Oxford, England). 2014;30(9):1312–3.CrossRef Stamatakis A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics (Oxford, England). 2014;30(9):1312–3.CrossRef
27.
go back to reference Chochua S, et al. Emergent Invasive Group A Streptococcus dysgalactiae subsp. equisimilis, United States, 2015–2018. Emerg Infect Dis. 2019;25(8):1543–7.CrossRef Chochua S, et al. Emergent Invasive Group A Streptococcus dysgalactiae subsp. equisimilis, United States, 2015–2018. Emerg Infect Dis. 2019;25(8):1543–7.CrossRef
28.
go back to reference Rothman KJ. No adjustments are needed for multiple comparisons. Epidemiology. 1990;1(1):43–6.CrossRef Rothman KJ. No adjustments are needed for multiple comparisons. Epidemiology. 1990;1(1):43–6.CrossRef
29.
go back to reference Salman S, et al. Pharmacokinetics of transfer of azithromycin into the breast milk of african mothers. Antimicrob Agents Chemother. 2015;60(3):1592–9.CrossRef Salman S, et al. Pharmacokinetics of transfer of azithromycin into the breast milk of african mothers. Antimicrob Agents Chemother. 2015;60(3):1592–9.CrossRef
30.
go back to reference Vodstrcil LA, et al. Measurement of tissue azithromycin levels in self-collected vaginal swabs post treatment using liquid chromatography and tandem mass spectrometry (LC-MS/MS). PLoS One. 2017;12(5):e0177615.CrossRef Vodstrcil LA, et al. Measurement of tissue azithromycin levels in self-collected vaginal swabs post treatment using liquid chromatography and tandem mass spectrometry (LC-MS/MS). PLoS One. 2017;12(5):e0177615.CrossRef
31.
go back to reference Levison ME, Levison JH. Pharmacokinetics and pharmacodynamics of antibacterial agents. Infect Dis Clin North Am. 2009;23(4):791–vii.CrossRef Levison ME, Levison JH. Pharmacokinetics and pharmacodynamics of antibacterial agents. Infect Dis Clin North Am. 2009;23(4):791–vii.CrossRef
32.
go back to reference Ciszewski M, Szewczyk EM. Potential factors enabling human body colonization by animal Streptococcus dysgalactiae subsp. equisimilis strains. Curr Microbiol. 2017;74(5):650–4.CrossRef Ciszewski M, Szewczyk EM. Potential factors enabling human body colonization by animal Streptococcus dysgalactiae subsp. equisimilis strains. Curr Microbiol. 2017;74(5):650–4.CrossRef
33.
go back to reference Yamaoka S, et al. Neonatal streptococcal toxic shock syndrome caused by Streptococcus dysgalactiae subsp. equisimilis. Pediatr Infect Dis J. 2010;29(10):979–81.CrossRef Yamaoka S, et al. Neonatal streptococcal toxic shock syndrome caused by Streptococcus dysgalactiae subsp. equisimilis. Pediatr Infect Dis J. 2010;29(10):979–81.CrossRef
34.
go back to reference Watanabe S, et al. Severe invasive streptococcal infection by Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis. Microbiol Immunol. 2016;60(1):1–9.CrossRef Watanabe S, et al. Severe invasive streptococcal infection by Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis. Microbiol Immunol. 2016;60(1):1–9.CrossRef
35.
go back to reference Loubinoux J, et al. Adult invasive and noninvasive infections due to Streptococcus dysgalactiae subsp. equisimilis in France from 2006 to 2010. J Clin Microbiol. 2013;51(8):2724–7.CrossRef Loubinoux J, et al. Adult invasive and noninvasive infections due to Streptococcus dysgalactiae subsp. equisimilis in France from 2006 to 2010. J Clin Microbiol. 2013;51(8):2724–7.CrossRef
36.
go back to reference Zhang Y, et al. Predominant role of msr(D) over mef(A) in macrolide resistance in Streptococcus pyogenes. Microbiology. 2016;162(1):46–52.CrossRef Zhang Y, et al. Predominant role of msr(D) over mef(A) in macrolide resistance in Streptococcus pyogenes. Microbiology. 2016;162(1):46–52.CrossRef
37.
go back to reference Tatsuno I, et al. Functional predominance of msr(D), which is more effective as mef(A)-associated than mef(E)-associated, over mef(A)/mef(E) in macrolide resistance in Streptococcus pyogenes. Microb Drug Resist. 2018;24(8):1089–97.CrossRef Tatsuno I, et al. Functional predominance of msr(D), which is more effective as mef(A)-associated than mef(E)-associated, over mef(A)/mef(E) in macrolide resistance in Streptococcus pyogenes. Microb Drug Resist. 2018;24(8):1089–97.CrossRef
38.
go back to reference Martin J. The Streptococcus pyogenes Carrier State, in Streptococcus pyogenes: basic biology to clinical manifestations. In: Ferretti JJ, Stevens DL, Fischetti VA, editors. Oklahoma City (OK). 2016. Martin J. The Streptococcus pyogenes Carrier State, in Streptococcus pyogenes: basic biology to clinical manifestations. In: Ferretti JJ, Stevens DL, Fischetti VA, editors. Oklahoma City (OK). 2016.
Metadata
Title
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
Authors
Isatou Jagne
Alexander J. Keeley
Abdoulie Bojang
Bully Camara
Edrissa Jallow
Elina Senghore
Claire Oluwalana
Saikou Y. Bah
Claire E. Turner
Abdul Karim Sesay
Umberto D’Alessandro
Christian Bottomley
Thushan I. de Silva
Anna Roca
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2022
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-022-07080-4

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