New study shows a single two-gram oral dose of azithromycin at normal birth can reduce 33% maternal sepsis, deaths

A recent multicountry study called Azithromycin Prophylaxis in Labor Use Study (A-PLUS) has found that a single dose of two-gram azithromycin antibiotic taken orally during vaginal delivery, commonly known as normal delivery, can significantly reduce the risk of maternal sepsis or death.

Sepsis is a severe medical condition that occurs when the body responds excessively to an infection, which can result in multiple organ failures and death.

The findings of the study have recently been published in the New England Journal of Medicine.

The study was conducted by the Global Network for Women's and Children's Health Research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of which icddr,b is a partner.

The A-PLUS trial enrolled women in labour from Bangladesh, the Democratic Republic of the Congo, Guatemala, India, Kenya, Pakistan, and Zambia.

Between September 2020 and August 2022, 29,278 women were randomised to receive either azithromycin or a placebo.

The risk of maternal sepsis or death was 33% lower in the azithromycin group compared to the placebo (look-alike dummy, which does not contain the study drug) group.

The difference in the outcome was mainly due to the lower occurrence of sepsis in the azithromycin group than in the placebo group.

Additionally, women receiving azithromycin were less likely to develop infections, including endometritis (infection of the lining of the womb), wound infections, and urine infections.

Women receiving azithromycin also had fewer hospital readmissions and unscheduled healthcare visits compared to the placebo group.

The findings from interim analysis of the study were so impactful that one of the trial sites (Democratic Republic of the Congo) stopped enrolling new participants early to ensure that as many women as possible could benefit as soon as possible.

However, the study could not find azithromycin to have any impact on neonatal sepsis or death. It is also to be noted that azithromycin has been in use for caesarean delivery to prevent and manage infections.

The Bangladesh site of the study was co-led by Dr Rashidul Haque, an Emeritus Scientist and Sk Masum Billah, an Associate Scientist at icddr,b and Dr William Petri at the University of Virginia, USA.

Commenting on the implication of the study Dr Haque said that in Bangladesh, where about two out of three deliveries are normal, a single dose of two-gram azithromycin given during labour as a preventive measure can help save many lives.

He hopes that healthcare providers and policymakers will consider using azithromycin as a preventive measure during vaginal deliveries.

These findings have the potential to change clinical practice by providing a safe, effective and low-cost approach to reduce the global burden of maternal sepsis and death, said Diana W. Bianchi, M.D., director of NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the primary funder of the trial.

"We urgently need effective strategies to prevent pregnancy-related infections, which account for roughly 10% of maternal deaths worldwide."

The study also found that azithromycin was not associated with an increased risk of adverse events. The researchers hope that their findings will inform the development of new strategies to prevent maternal sepsis and death.

This multi-site study was conducted by NICHD's Global Network for Women's and Children's Health Research and was co-funded by NICHD and the FNIH, with support to FNIH provided by a grant from the Bill & Melinda Gates Foundation.