Oral azithromycin given during labour decreases bacterial carriage in the mothers and their offspring: a double-blind randomized trial

Abstract

Bacterial sepsis remains a leading cause of death among neonates with Staphylococcus aureus, group B streptococcus (GBS) and Streptococcus pneumoniae identified as the most common causative pathogens in Africa. Asymptomatic bacterial colonization is an intermediate step towards sepsis. We conducted a phase III, double-blind, placebo-controlled randomized trial to determine the impact of giving one oral dose of azithromycin to Gambian women in labour on the nasopharyngeal carriage of S. aureus, GBS or S. pneumoniae in the newborn at day 6 postpartum. Study participants were recruited in a health facility in western Gambia. They were followed for 8 weeks and samples were collected during the first 4 weeks. Between April 2013 and April 2014 we recruited 829 women who delivered 843 babies, including 13 stillbirths. Sixteen babies died during the follow-up period. No maternal deaths were observed. No serious adverse events related to the intervention were reported. According to the intent-to-treat analysis, prevalence of nasopharyngeal carriage of the bacteria of interest in the newborns at day 6 was lower in the intervention arm (28.3% versus 65.1% prevalence ratio 0.43; 95% CI 0.36–0.52, p <0.001). At the same time-point, prevalence of any bacteria in the mother was also lower in the azithromycin group (nasopharynx, 9.3% versus 40.0%, p <0.001; breast milk, 7.9% versus 21.6%, p <0.001; and the vaginal tract, 13.2% versus 24.2%, p <0.001). Differences between arms lasted for at least 4 weeks. Oral azithromycin given to women in labour decreased the carriage of bacteria of interest in mothers and newborns and may lower the risk of neonatal sepsis.Trial registrationClinicalTrials.gov Identifier NCT01800942.

Azithromycin in Labor Lowers Clinical Infections in Mothers and Newborns: A Double-Blind Trial

“…12 This is the case in SSA, where most of the population is poorly nourished, women often deliver in unhygienic conditions, female genital mutilation is common practice, 18 -20 tears and episiotomies are frequent, the rate of bacterial colonization is high (in the vaginal tract and in breast milk), 16 and, importantly, most personnel attending deliveries are poorly trained to identify pregnancies at high risk of neonatal or puerperal sepsis. Our study shows that in this setting, the prophylactic use of 1 oral dose of azithromycin, an antibiotic that is not used for clinical care in The Gambia, has the potential to reduce the risk of infections among women in the puerperal period and among their offspring during the neonatal period.…”

“…This may be due to the local practice of applying shea butter to the umbilical stump, which has been shown to be protective. 25 In the azithromycin group, the lower incidence of these infections, as well as of otitis and conjunctivitis, probably reflects the effect of the intervention on colonization by S aureus and Streptococcus species in the newborns, 16 because these bacteria are major causes of both conditions. 26 -28 The absence of an effect of the intervention on oral infections may reflect the antiinflamatory effects of breast milk that are protective of such lesions in this early neonatal period.…”

“…33 Our study differed from these previous studies because it was the first to administer azithromycin to women in labor. The primary outcome of the trial was bacterial carriage 16 and the analysis of clinical outcomes, which we report in this article, was conducted post hoc. A limitation of our analysis is that clinical conditions were not predefined and were based on clinical assessment, without laboratory confirmation.…”

“…15 The study was designed to determine the effect of the intervention on bacterial carriage (S aureus, GBS, and S pneumoniae) in nasopharyngeal swabs, breast milk samples, and vaginal swabs collected up to 28 days after delivery. 16 Azithromycin substantially reduced bacterial carriage in both the mother and the newborn and also reduced the use of antibiotics during the puerperal period by 60%. In this article, we present a post hoc analysis of the effect of the intervention on the occurrence of maternal and neonatal fever, malaria and, clinical infections during the 8-week follow-up period.…”

“…The detailed study protocol 15 and the main results 16 have been published elsewhere. Briefly, this was a phase-III, double-blind, placebo-controlled, randomized trial in which pregnant women in labor were randomized to receive a single dose of 2 g of oral azithromycin or placebo (ratio 1:1).…”