Prevention of bacterial infections in the newborn by pre-delivery administration of azithromycin: Study protocol of a randomized efficacy trial

Abstract

BackgroundNeonatal deaths, estimated at approximately 4 million annually, now account for almost 40 % of global mortality in children aged under-five. Bacterial sepsis is a leading cause of neonatal mortality. Assuming the mother is the main source for bacterial transmission to newborns, the primary objective of the trial is to determine the impact of one oral dose of azithromycin, given to women in labour, on the newborn’s bacterial carriage in the nasopharynx. Secondary objectives include the impact of the intervention on bacterial colonization in the baby and the mother during the first month of life.Methods/designThis is a Phase III, double -blind, placebo controlled randomized clinical trial in which 830 women in labour were randomized to either a single dose of 2 g oral azithromycin or placebo (ratio 1:1). The trial included pregnant women in labour aged 18 to 45 years attending study health centres in the Western Gambia. A post-natal check of the mother and baby was conducted at the health centre by study clinicians before discharge and 8–10 days after delivery. Home follow up visits were conducted daily during the first week and then weekly until week 8 after delivery. Vaginal swabs and breast milk samples were collected from the mothers, and the pathogens Streptococcus pneumoniae, Group B Streptococcus (GBS) and Staphylococcus aureus were isolated from the study samples. For bacterial isolates, susceptibility pattern to azithromycin was determined using disk diffusion and E-test. Eye swabs were collected from newborns with eye discharge during the follow up period, and Chlamydial infection was assessed using molecular methods.DiscussionThis is a proof-of-concept study to assess the impact of antibiotic preventive treatment of women during labour on bacterial infections in the newborn. If the trial confirms this hypothesis, the next step will be to assess the impact of this intervention on neonatal sepsis. The proposed intervention should be easily implementable in developing countries.Trial registrationClinicalTrials.gov Identifier -NCT01800942- First received: February 26, 2013.

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

“…We have recently concluded a proofof-concept double-blind trial in a periurban health facility in Western Gambia where women in labor were randomized to receive either an oral dose of 2 g of azithromycin or placebo. 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%.…”

“…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).…”

“…The randomization list was created by an independent data manager and IDIFARMA numbered the blisters according to the list. 15 One blister pack of IMP contained 4 tablets of 0.5 g (2 g total) of either azithromycin or placebo. The active drug and the placebo looked identical.…”

Maternal pneumococcal nasopharyngeal carriage and risk factors for neonatal carriage after the introduction of pneumococcal conjugate vaccines in The Gambia

“…All NPS were collected in accordance with the WHO protocol for detecting S. pneumoniae in the upper respiratory tract [27] and as described previously [28].…”

“…Stored NPS were plated on appropriate agar for selective isolation of S. pneumoniae and Staphylococcus aureus [28]. All pneumococcal isolates were serotyped by using the latex agglutination test (Statens Serum Institute, Copenhagen, Denmark) [29].…”