Impact of prophylactic oral azithromycin during labor on Azithromycin Resistance (AMR) in nasal Staphylococcus aureus and Streptococcus pneumoniae in women and infants in the multi-country Azithromycin Prevention in Labor Use Study (A-PLUS)

BACKGROUND: Prophylactic oral azithromycin vs. placebo reduced maternal, but not neonatal, mortality/sepsis in the A-PLUS Randomized Trial. While prophylactic intrapartum azithromycin reduces maternal mortality/sepsis, it may promote antimicrobial resistance (AMR) in commensal bacteria,. METHODS: Randomly selected women and their infants participating in A-PLUS were enrolled in a longitudinal cross-sectional sub-study to assess the presence of azithromycin resistance in selected bacteria in nasal cultures. Staphylococcus aureus and Streptococcus pneumoniae were cultured on selective agar, then azithromycin-containing agar to select for azithromycin resistant bacteria, identified biochemically. Azithromycin susceptibility was assessed by E-test. Nasal cultures were collected from women and infants between August 11, 2021 and September 18, 2023 during labor/day 1, day 7, 6 weeks, and 3, 6 and 12 months after delivery. RESULTS: The study enrolled 911 women and 915 liveborn infants at 8 sites in 7 countries. Azithromycin resistance in S aureus was higher and azithromycin susceptibility was lower in women receiving azithromycin compared with those receiving placebo on day 7 (P < 0.001), 6 weeks (P < 0.001) and 3 months (P = 0.009) after delivery. Azithromycin resistance in S aureus was also higher and azithromycin susceptibility was lower 6 weeks after delivery (P < 0.001) in infants born to women receiving azithromycin, Azithromycin resistance in S. pneumoniae was too sparse to interpret. CONCLUSIONS: There was an increase in prevalence of azithromycin resistance (or reduction in azithromycin susceptibility) in commensal nasal S. aureus between day 7, 6 weeks and 3 months in women exposed to azithromycin vs. placebo and only at 6 weeks in infants exposed to azithromycin vs. placebo. These differences between the azithromycin and placebo groups were no longer detected at 6 and 12 months post-partum in the women and after 6 weeks through 12 months in the infants.

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Journal
PLoS ONE
Published
2026-04-17
DOI
https://doi.org/10.1371/journal.pone.0346174
Primary Topic
Neonatal and Maternal Infections
Type
article
Field-Weighted Citation Impact
0.00

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article

Impact of prophylactic oral azithromycin during labor on Azithromycin Resistance (AMR) in nasal Staphylococcus aureus and Streptococcus pneumoniae in women and infants in the multi-country Azithromycin Prevention in Labor Use Study (A-PLUS)

Akila Subramaniam, Marissa Trotta, Denise C. Babineau, Sixto M. Leal et al.
PLoS ONE
Neonatal and Maternal Infections
article

Impact of prophylactic oral azithromycin during labor on Azithromycin Resistance (AMR) in nasal Staphylococcus aureus and Streptococcus pneumoniae in women and infants in the multi-country Azithromycin Prevention in Labor Use Study (A-PLUS)

Akila Subramaniam, Marissa Trotta, Denise C. Babineau, Sixto M. Leal, Patricia L. Hibberd, Doyle V. Ward, Melissa Bauserman, Adrien Lokangaka, Dr Manjunath Somannavar, Manolo Mazariegos, Jean Kim, Elwyn Chomba, Sk Masum Billah, William A. Petri, Anna Aceituno, Rashidun Haque, Robert L. Goldenberg, Sarah Saleem, Fabian Esamai, Antoinette Tshefu, Muska Mwenchanya, Richard J. Derman, Imran Ahmed, Waldemar A. Carlo, Archana Patel, Nancy F. Krebs, Alan T. N. Tita, Sherri Bucher, Elizabeth M. McClure, Shivaprasad S. Goudar, Marion Koso-Thomas
article en

Abstract

BACKGROUND: Prophylactic oral azithromycin vs. placebo reduced maternal, but not neonatal, mortality/sepsis in the A-PLUS Randomized Trial. While prophylactic intrapartum azithromycin reduces maternal mortality/sepsis, it may promote antimicrobial resistance (AMR) in commensal bacteria,. METHODS: Randomly selected women and their infants participating in A-PLUS were enrolled in a longitudinal cross-sectional sub-study to assess the presence of azithromycin resistance in selected bacteria in nasal cultures. Staphylococcus aureus and Streptococcus pneumoniae were cultured on selective agar, then azithromycin-containing agar to select for azithromycin resistant bacteria, identified biochemically. Azithromycin susceptibility was assessed by E-test. Nasal cultures were collected from women and infants between August 11, 2021 and September 18, 2023 during labor/day 1, day 7, 6 weeks, and 3, 6 and 12 months after delivery. RESULTS: The study enrolled 911 women and 915 liveborn infants at 8 sites in 7 countries. Azithromycin resistance in S aureus was higher and azithromycin susceptibility was lower in women receiving azithromycin compared with those receiving placebo on day 7 (P < 0.001), 6 weeks (P < 0.001) and 3 months (P = 0.009) after delivery. Azithromycin resistance in S aureus was also higher and azithromycin susceptibility was lower 6 weeks after delivery (P < 0.001) in infants born to women receiving azithromycin, Azithromycin resistance in S. pneumoniae was too sparse to interpret. CONCLUSIONS: There was an increase in prevalence of azithromycin resistance (or reduction in azithromycin susceptibility) in commensal nasal S. aureus between day 7, 6 weeks and 3 months in women exposed to azithromycin vs. placebo and only at 6 weeks in infants exposed to azithromycin vs. placebo. These differences between the azithromycin and placebo groups were no longer detected at 6 and 12 months post-partum in the women and after 6 weeks through 12 months in the infants.

PLoS ONEVol. 21(4)
Boston University (US), University of North Carolina at Chapel Hill (US), Aga Khan University (PK), Indiana University Health (US), The University of Sydney (AU), Ministry of Public Health (CD), Statistical and Applied Mathematical Sciences Institute (US), Moi University (KE), Thomas Jefferson University (US), University of Massachusetts Chan Medical School (US), RTI International (US), International Centre for Diarrhoeal Disease Research (BD), University Teaching Hospital (ZM), University of Alabama at Birmingham (US), University of Zambia (ZM), Lata Medical Research Foundation (IN), Jawaharlal Nehru Medical College (IN), Datta Meghe Institute of Higher Education and Research (IN), Institute of Nutrition of Central America and Panama (GT), Eunice Kennedy Shriver National Institute of Child Health and Human Development (US), UMass Memorial Medical Center (US), University of Virginia (US), Indiana University – Purdue University Indianapolis (US), Columbia University (US), University of Colorado Denver (US)
Bill and Melinda Gates Foundation, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Openalex Percentile: Top 16%
Neonatal and Maternal Infections
DOIOpen Access PDFOpenAlex
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