Oral azithromycin during labor fails to stop neonatal sepsis, death

Randomized trials in The Gambia and Burkina Faso found that giving mothers azithromycin during labor did not reduce the incidence of neonatal sepsis or mortality.

Of approximately 12,000 live births in two West African countries, the primary outcome of neonatal sepsis or mortality at 28 days was 2.0% with intrapartum oral azithromycin and 1.9% with placebo (OR 1.06, 95% CI 0.80-1.38, P.=0.70), reported by Dr. Anna Roca and colleagues of the MRC Unit The Gambia, London School of Hygiene and Tropical Medicine, Fajara, Gambia.

When assessed separately, rates of neonatal mortality and sepsis were similar in the two study groups, 0.8% and 1.3%, respectively. jam.

There were fewer cases of culture-confirmed sepsis in neonates in the azithromycin group (13 vs. 24 in the placebo group), but this difference was not significant. Staphylococcus aureus was the most commonly isolated bacterium (2 in the azithromycin group and 6 in the placebo group), accounting for 59.5% of confirmed Gram-negative cases.

“Why is the effect of azithromycin during labour? Staphylococcus aureus Colonization and noninvasive disease did not lead to a reduction in neonatal sepsis or neonatal mortality,” Roca and co-authors wrote.

“Sepsis and bacteriologically confirmed sepsis may be caused by different pathogens, and Gram-negative bacteria, viruses, and/or fungi may be the more common causes of clinical sepsis.” “Another explanation is that a decrease in sepsis caused by some etiologies is balanced by an increase in other etiologies,” they continued.

Among neonatal secondary outcomes, the azithromycin group had a significantly lower incidence of clinical skin infections (0.8% vs. 1.7% in the placebo group) and less antibiotic use (6.2% vs. 7.8%; P.<0.001 for both), with a significantly lower probability of infection (3% vs. 4.4%).

Among mothers, the azithromycin-treated group had a lower incidence of mastitis (0.3% vs. 0.5% in the placebo group) and puerperal fever (0.1% vs. 0.3%, P.=0.04 for both), the result is ” A Trial of Azithromycin in Caesarean Delivery A study conducted in the United States found that azithromycin halved severe maternal infections,” the authors point out.

Current research mothers (PregnAnZI-2) also had a significantly lower probability of infection with broad-spectrum macrolides (0.4% vs. 0.7% with placebo).

“Early evaluations of mass drug campaigns to control trachoma in sub-Saharan Africa suggest that azithromycin Reduced carriage of bacteria apart from chlamydia trachomatis Child mortality has been significantly reduced,” Roca and colleagues write in the foreword.

“Subsequently, a large cluster-randomized trial in sub-Saharan Africa found that high-dose azithromycin reduced mortality The effect is stronger in children under 5 years of age and stronger in infants under 6 months,” the team continued. Proof of concept trial Administration of oral azithromycin during labor reduced gram-positive carriage over the subsequent 4 weeks, and a post-hoc analysis found a reduction in mild-to-moderate disease in both birthing parents and neonates. . “

Recently, Randomized A-PLUS trial — Trials conducted in low- and middle-income countries in Asia, Africa, and Latin America showed that a single dose of azithromycin given to the mother during vaginal delivery was associated with a higher risk of maternal sepsis or death than placebo. showed a significant reduction in comparison (1.6% vs 2.4%). %). However, the intervention made no difference in the incidence of stillbirth, neonatal death, or sepsis.

“Neonatal mortality remains a stubborn problem,” write Stephanie Schrag, M.D., of the CDC and Cynthia Whitney, M.D., M.P.H., Emory University, both in Atlanta. Accompanying editorial“Evidence suggests that complications of labor and delivery play a major role in mortality in the first few hours of life, with preterm birth and infections each causing about one-third of deaths in the first weeks of life.” increase.”

They noted that factors other than sepsis may have influenced mortality in the current study. Sudden death and aspiration were commonly cited as causes of death.”

Despite the fact that antibiotics may have provided some benefit for some secondary endpoints, Schrag and Whitney concluded that antibiotic interventions were associated with “an increase in cardiac QT interval prolongation and reported sudden death.” It should be approached with caution as it may lead to serious adverse events, he warned. Among the subset of susceptible individuals taking azithromycin. “

Additionally, antibiotic resistance and growing evidence that antibiotics can disrupt maternal and neonatal microbiomes should also be considered. As such, while the current trial results are “disappointing,” Schrag and Whitney said several other efforts underway to advance the field show promise.

From October 2017 to May 2021, PregnAnZI-2 randomized 11,983 pregnancies from Gambia (55%) and Burkina Faso (45%) in a 1:1 ratio to intervention or placebo. bottom.

Overall, 11,783 births met the criteria for primary analysis (neonatal deaths due to asphyxia, low birth weight, and severe congenital malformations were excluded).

Of the 5,889 infants in the azithromycin group, the overall primary endpoint occurred in 115 neonates, with 79 sepsis and 47 deaths. Of 5,984 live births in the placebo group, primary endpoint events occurred in 111 newborns, 78 of whom died of sepsis and 45 of whom died.

There were 8 maternal deaths in the intervention group and 6 in the placebo group.

Limitations cited by Roca’s group included a low rate of microbiologically confirmed neonatal sepsis.As a result, bacteria that are easy to grow, such as: Staphylococcus aureus It may have been over-represented.

The study authors also highlighted a “notable difference” in early-onset sepsis between participants in Gambia and Burkina Faso, where some cases were missed due to travel distance to the study medical facility. In addition, late-onset sepsis may have been missed in The Gambia. “Because C-reactive protein was qualitatively measured and failed to meet the test criteria of 40mg/L.”