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. Early-neonatal sepsis is mainly due to intrapartum bacterial vertical transmission during delivery (in the birth canal) or during the first weeks of life as a result of the close physical contact with the mother if she carries pathogenic bacteria.
Asymptomatic bacterial colonization is a necessary and an intermediate step towards sepsis. Therefore, interventions aiming at blocking bacterial transmission from the mother to the newborn have the potential to reduce neonatal sepsis. A phase III, double-blind, placebo-controlled randomized trial was conducted at MRC Unit The Gambia lead by Dr Anna Roca, Principal Investigator of the study. The trial was conducted at Jammeh Foundation for Peace Hospital in collaboration with the health facility team.The trial was jointly funded by the Medical Research Council, UK and the UK Department for International Development (DFID). The main goal of the study was to determine the impact of giving one oral dose of azithromycin to Gambian women in labour on the nasopharyngeal carriage of S. aureus, GBS and S. pneumoniae in the newborn at day 6 postpartum.
Results, from the study, show that 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 study 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. Our study shows that one oral dose (2gr) of azithromycin given to women in labour decreased the carriage of bacteria of interest in mothers and newborns and, therefore, may lower the risk of maternal and neonatal sepsis.
Study participants were followed for 8 weeks and samples were collected during the first 4 weeks. In all, 1061 women in labour were assessed for eligibility and 829 (78.1%) were recruited, randomized and treated (414 azithromycin and 415 placebo). 829 of the women recruited 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.
When asked to comment Dr Anna Roca, said, “The trial was well conducted by a dedicated and competent multidisciplinary team. Our aim was to test the hypotheses that by giving azithromycin to women in labour, there would be an impact on bacterial carriage in the baby. Study results are very exciting. The reduction on bacterial colonization has been dramatic, and the next step should be a larger trial to assess the effect of this intervention on sepsis and mortality. On the other hand, we are also following the study babies to evaluate the long-term effect of the intervention and results will be analysed soon.”
The mothers and their newborns who participated in our study, Jammeh Foundation for Peace Hospital, MRCG staff and the Data Safety Monitor Board.
Anna Roca, Claire Oluwalana, Abdoulie Bojang, Bully Camara, Beate Kampmann, Robin Bailey, Adama Demba, Christian Bottomley, Umberto D’Alessandro.
Read more about the study on the Clinical Microbiology and Infection website: http://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(16)30020-9/abstract