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

A Roca, C Oluwalana, A Bojang, B Camara, B Kampmann, R Bailey, A Demba, C Bottomley, U D'Alessandro, A Roca, C Oluwalana, A Bojang, B Camara, B Kampmann, R Bailey, A Demba, C Bottomley, U D'Alessandro

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.

Keywords: Azithromycin; bacterial carriage; neonatal sepsis; randomized clinical trial; sub-Saharan Africa.

Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1
Fig. 1
Trial profile. Abbreviations: nb, Newborns; m, Mothers; NPSn, nasopharyngeal swabs collected from newborns; NPSm, nasopharyngeal swabs collected from mothers; BM, breast milk samples collected; VS, vaginal swabs collected. Some participants were still present until follow up but their samples were missed in some of the visits.
Fig. 2
Fig. 2
Bacterial carriage of Staphylococcus aureus, group B streptococci (GBS) and Streptococcus pneumoniae in the different study time points for the azithromycin (AZI) and placebo groups. (a) Newborn nasopharyngeal swabs (NPS); (b) Maternal NPS; (c) Breast milk sample.

References

    1. Seale A.C., Mwaniki M., Newton C.R., Berkley J.A. Maternal and early onset neonatal bacterial sepsis: burden and strategies for prevention in sub-Saharan Africa. Lancet Infect Dis. 2009;9:428–438.
    1. Cutland C.L., Madhi S.A., Zell E.R., Kuwanda L., Laque M., Groome M. Chlorhexidine maternal-vaginal and neonate body wipes in sepsis and vertical transmission of pathogenic bacteria in South Africa: a randomised, controlled trial. Lancet. 2009;374(9705):1909–1916.
    1. Waters D., Jawad I., Ahmad A., Luksic I., Nair H., Zgaga L. Aetiology of community-acquired neonatal sepsis in low and middle income countries. J Glob Health. 2011;1:154–170.
    1. Zaidi A.K., Thaver D., Ali S.A., Khan T.A. Pathogens associated with sepsis in newborns and young infants in developing countries. Pediatr Infect Dis J. 2009;28(1 Suppl. l):S10–S18.
    1. Chatzakis E., Scoulica E., Papageorgiou N., Maraki S., Samonis G., Galanakis E. Infant colonization by Staphylococcus aureus: role of maternal carriage. Eur J Clin Microbiol Infect Dis. 2011;30:1111–1117.
    1. Rudan I., Theodoratou E., Nair H., Marusic A., Campbell H. Reducing the burden of maternal and neonatal infections in low income settings. J Glob Health. 2011;1:106–109.
    1. Suara R.O., Adegbola R.A., Baker C.J., Secka O., Mulholland E.K., Greenwood B.M. Carriage of group B Streptococci in pregnant Gambian mothers and their infants. J Infect Dis. 1994;170:1316–1319.
    1. Drew R.H., Gallis H.A. Azithromycin–spectrum of activity, pharmacokinetics, and clinical applications. Pharmacotherapy. 1992;12:161–173.
    1. Nosten F., McGready R., D'Alessandro U., Bonell A., Verhoeff F., Menendez C. Antimalarial drugs in pregnancy: a review. Curr Drug Saf. 2006;1:1–15.
    1. Orton L.C., Omari A.A. Drugs for treating uncomplicated malaria in pregnant women. Cochrane Database Syst Rev. 2008;(4):CD004912.
    1. Fry A.M., Jha H.C., Lietman T.M., Chaudhary J.S., Bhatta R.C., Elliott J. Adverse and beneficial secondary effects of mass treatment with azithromycin to eliminate blindness due to trachoma in Nepal. Clin Infect Dis. 2002;35:395–402.
    1. Leach A.J., Shelby-James T.M., Mayo M., Gratten M., Laming A.C., Currie B.J. A prospective study of the impact of community-based azithromycin treatment of trachoma on carriage and resistance of Streptococcus pneumoniae. Clin Infect Dis. 1997;24:356–362.
    1. Harding-Esch E.M., Edwards T., Mkocha H., Munoz B., Holland M.J., Burr S.E. Trachoma prevalence and associated risk factors in the gambia and Tanzania: baseline results of a cluster randomised controlled trial. PLoS Negl Trop Dis. 2010;4(11):e861.
    1. Burr S.E., Milne S., Jafali J., Bojang E., Rajasekhar M., Hart J. Mass administration of azithromycin and Streptococcus pneumoniae carriage: cross-sectional surveys in the Gambia. Bull World Health Organ. 2014;92:490–498.
    1. Porco T.C., Gebre T., Ayele B., House J., Keenan J., Zhou Z. Effect of mass distribution of azithromycin for trachoma control on overall mortality in Ethiopian children: a randomized trial. JAMA. 2009;302:962–968.
    1. van den Broek N.R., White S.A., Goodall M., Ntonya C., Kayira E., Kafulafula G. The APPLe study: a randomized, community-based, placebo-controlled trial of azithromycin for the prevention of preterm birth, with meta-analysis. PLoS Med. 2009;6(12):e1000191.
    1. Unger H.W., Ome-Kaius M., Wangnapi R.A., Umbers A.J., Hanieh S., Suen C.S. Sulphadoxine-pyrimethamine plus azithromycin for the prevention of low birthweight in Papua New Guinea: a randomised controlled trial. BMC Med. 2015;13:9.
    1. Di Renzo G.C., Melin P., Berardi A., Blennow M., Carbonell-Estrany X., Donzelli G.P. Intrapartum GBS screening and antibiotic prophylaxis: a European consensus conference. J Matern Fetal Neonatal Med. 2015;28:766–782.
    1. Schrag S.J., Verani J.R. Intrapartum antibiotic prophylaxis for the prevention of perinatal group B streptococcal disease: experience in the United States and implications for a potential group B streptococcal vaccine. Vaccine. 2013;31(Suppl. 4):D20–D26.
    1. Sigauque B., Roca A., Mandomando I., Morais L., Quinto L., Sacarlal J. Community-acquired bacteremia among children admitted to a rural hospital in Mozambique. Pediatr Infect Dis J. 2009;28:108–113.
    1. Roca A., Oluwalana C., Camara B., Bojang A., Burr S., Davis T.M. Prevention of bacterial infections in the newborn by pre-delivery administration of azithromycin: study protocol of a randomized efficacy trial. BMC Pregnancy Childbirth. 2015;15:302.
    1. Jasseh M., Webb E.L., Jaffar S., Howie S., Townend J., Smith P.G. Reaching millennium development goal 4-the Gambia. Trop Med Int Health. 2011;16:1314–1325.
    1. Bottomley C., Bojang A., Smith P.G., Darboe O., Antonio M., Foster-Nyarko E. The impact of childhood vaccines on bacterial carriage in the nasopharynx: a longitudinal study. Emerg Themes Epidemiol. 2015;12:1.
    1. Salman S., Davis T.M., Page-Sharp M., Camara B., Oluwalana C., Bojang A. Pharmacokinetics of transfer of azithromycin into the breast milk of African mothers. Antimicrob Agents Chemother. 2015 Dec 28
    1. Unger H.W., Aho C., Ome-Kaius M., Wangnapi R.A., Umbers A.J., Jack W. Impact of intermittent preventive treatment in pregnancy with azithromycin-containing regimens on maternal nasopharyngeal carriage and antibiotic sensitivity of Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus—a cross-sectional survey at delivery. J Clin Microbiol. 2015 Feb 11
    1. Revised guidelines for prevention of early-onset group B streptococcal (GBS) infection American Academy of Pediatrics Committee on Infectious Diseases and Committee on Fetus and Newborn. Pediatrics. 1997;99:489–496.
    1. Andersson D.I., Hughes D. Antibiotic resistance and its cost: is it possible to reverse resistance? Nat Rev Microbiol. 2010;8:260–271.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する