Long-term Impact of Oral Azithromycin Taken by Gambian Women During Labor on Prevalence and Antibiotic Susceptibility of Streptococcus pneumoniae and Staphylococcus aureus in Their Infants: Follow-up of a Randomized Clinical Trial.

Background: Oral azithromycin given to women in labor decreases maternal and neonatal bacterial carriage but increases azithromycin-resistant bacteria during at least 4 weeks following the intervention. We assessed the prevalence of bacterial carriage and azithromycin resistance 12 months after treatment among study infants. Methods: Nasopharyngeal swabs (NPSs) were collected between November 2014 and May 2015 from children aged 11-13 months whose mothers had received azithromycin or placebo during labor. Streptococcus pneumoniae and Staphylococcus aureus were isolated using conventional microbiological methods. Antibiotic susceptibility was determined by disk diffusion and confirmed by Etest or VITEK-2. Results: NPSs were collected from 461 children. The prevalence of S. pneumoniae and S. aureus was similar between children from the azithromycin and placebo arms (85.0% vs 82.1%; odds ratio [OR], 1.23 [95% confidence interval {CI}, .73-2.08] for S. pneumoniae and 21.7% vs 21.3%; OR, 1.02 [95% CI, .64-1.64] for S. aureus). Prevalence of azithromycin-resistant S. pneumoniae was similar in both arms (1.8% vs 0.9% in children from the azithromycin and placebo arms, respectively; OR, 2.10 [95% CI, .30-23.38]); resistance to other antibiotics was also similar between arms. For S. aureus, there was no difference in azithromycin resistance between children in the azithromycin (3.1%) and placebo (2.6%) arms (OR, 1.22 [95% CI, .35-4.47]) or resistance to any other antibiotics. Conclusions: The higher prevalence of S. aureus azithromycin resistance observed among women treated during labor and their babies 4 weeks after treatment had waned 12 months after delivery. Azithromycin intervention did not induce other antibiotic resistance to S. pneumoniae or S. aureus. Clinical Trials Registration: NCT01800942

Additional file 1 of Impact of intra-partum azithromycin on carriage of group A streptococcus in the Gambia: a posthoc analysis of a double-blind randomized placebo-controlled trial

Whole Genome Sequencing Data

Pre-delivery administration of azithromycin to prevent neonatal sepsis and death: a phase iii double-blind randomized clinical trial (PregnAnZI-2 trial).

BACKGROUND: Despite reduction in the risk of under-5 mortality in the last decade and a half, neonatal deaths have remained stable globally. Gram-positive bacterial infections are leading causes of neonatal sepsis and death. Because the mother is an important source for bacterial transmission to babies during the perinatal period, interventions that lower risk of transmission can potentially reduce invasive bacterial infections. The primary objective of the trial will assess the effect of intrapartum azithromycin on neonatal sepsis and mortality. Secondary objectives include the impact of the intervention on prevalence of carriage and resistance, puerperal infections, and infant growth. METHODS: This is a phase III, double-blinded, placebo-controlled randomized trial in which 12,000 women in labour are randomized to either a single dose of 2 g of oral azithromycin (AZI) or placebo in The Gambia and Burkina Faso. Mother/newborn pairs are followed-up at 28-days post-delivery to assess health and mortality. Passive visits are conducted to collect adverse events including hospitalizations. When clinically indicated, samples are collected for assessment of neonatal and puerperal sepsis. A cohort of 250 mother/newborn pair per country have been included in the carriage sub-study to assess bacterial colonization at day 0, 6, 28 and 4 months. Children of the first 1000 mothers recruited in each country are followed-up at 6 and 12 months for anthropometric assessments. CONCLUSIONS: If successful, this simple implementable intervention has the potential to achieve wide coverage in Sub-Saharan Africa (SSA) where low-cost interventions to reduce neonatal sepsis and mortality and morbidity in mothers are urgently needed. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov: NCT0319954