Effect of Probiotics on GBS Colonization Status During Pregnancy: A Pilot Randomized Controlled Trial

Summary

Group B Streptococcus (GBS) is the leading cause of neonatal morbidity and mortality in Canada. It may be passed from a study participant colonized in the genital tract by GBS to their baby during vaginal birth. While approximately 10 to 30% of pregnant people harbour GBS in the vagina or rectum, the incidence of neonatal GBS disease is 1 to 2 infants per 1000 births. The use of intrapartum antibiotics to treat colonized individuals with or without risk factors has led to a 70% decline in the incidence of early-onset GBS sepsis in the past decade. Despite this impressive decline, antibiotic resistance has become a major public health concern. Association between intrapartum antibiotic use and ampicillin resistance in E. coli isolated from neonates has previously been documented. Furthermore, while GBS has remained sensitive to penicillin, 20% are resistant to erythromycin and clindamycin, which are alternate drugs for patients allergic to penicillin. Alternative approaches are therefore needed to reduce the risk of GBS infection. We therefore propose to study the use of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 (Lactobacillus fermentum RC-14) in the colonization status of GBS in pregnant people. Lactobacilli are part of normal gut and vaginal flora and have been widely used as probiotics to treat various conditions. In particular, these two strains have shown to be beneficial in the treatment of urinary tract infections and bacterial vaginosis. Our study design involves recruiting two hundred pregnant people (one hundred in each arm) through various midwifery practices in the GTA at the end of their first trimester of pregnancy. These individuals will be randomized to receive probiotics or placebo for twelve weeks of their pregnancies and will be cultured before delivery to determine their colonization status. The capsules with probiotics and placebo will be provided free of charge. The study design was chosen to minimize the cost and clients' visits to the clinic as vaginal/rectal swabs are routinely offered at 35-37 weeks of gestation.

Timeline

Start

2015-08

Primary completion

2016-06

Completion

2016-07

Publications

• Background Stoll BJ, Hansen NI, Sanchez PJ, Faix RG, Poindexter BB, Van Meurs KP, Bizzarro MJ, Goldberg RN, Frantz ID 3rd, Hale EC, Shankaran S, Kennedy K, Carlo WA, Watterberg KL, Bell EF, Walsh MC, Schibler K, Laptook AR, Shane AL, Schrag SJ, Das A, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues. Pediatrics. 2011 May;127(5):817-26. doi: 10.1542/peds.2010-2217. Epub 2011 Apr 25.
• Background Verani JR, McGee L, Schrag SJ; Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC). Prevention of perinatal group B streptococcal disease--revised guidelines from CDC, 2010. MMWR Recomm Rep. 2010 Nov 19;59(RR-10):1-36.
• Background Darling E, Saurette K. Clinical Practice Guideline No.11: Group B Streptococcus: Prevention and Management in Labour. Toronto: Association of Ontario Midwives 2010.
• Background Money DM, Dobson S; Canadian Paediatric Society, Infectious Diseases Commitee. RETIRED: The prevention of early-onset neonatal group B streptococcal disease. J Obstet Gynaecol Can. 2004 Sep;26(9):826-40. doi: 10.1016/s1701-2163(16)30157-8. English, French.
• Background Kalliomaki M, Salminen S, Isolauri E. Positive interactions with the microbiota: probiotics. Adv Exp Med Biol. 2008;635:57-66. doi: 10.1007/978-0-387-09550-9_5.
• Background Reid G, Dols J, Miller W. Targeting the vaginal microbiota with probiotics as a means to counteract infections. Curr Opin Clin Nutr Metab Care. 2009 Nov;12(6):583-7. doi: 10.1097/MCO.0b013e328331b611.
• Background Anukam K, Osazuwa E, Ahonkhai I, Ngwu M, Osemene G, Bruce AW, Reid G. Augmentation of antimicrobial metronidazole therapy of bacterial vaginosis with oral probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14: randomized, double-blind, placebo controlled trial. Microbes Infect. 2006 May;8(6):1450-4. doi: 10.1016/j.micinf.2006.01.003. Epub 2006 Mar 29.
• Background Martinez RC, Franceschini SA, Patta MC, Quintana SM, Gomes BC, De Martinis EC, Reid G. Improved cure of bacterial vaginosis with single dose of tinidazole (2 g), Lactobacillus rhamnosus GR-1, and Lactobacillus reuteri RC-14: a randomized, double-blind, placebo-controlled trial. Can J Microbiol. 2009 Feb;55(2):133-8. doi: 10.1139/w08-102.
• Background Martinez RC, Franceschini SA, Patta MC, Quintana SM, Candido RC, Ferreira JC, De Martinis EC, Reid G. Improved treatment of vulvovaginal candidiasis with fluconazole plus probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14. Lett Appl Microbiol. 2009 Mar;48(3):269-74. doi: 10.1111/j.1472-765X.2008.02477.x. Epub 2009 Feb 2.
• Background Reid G, Kirjaivanen P. Taking probiotics during pregnancy. Are they useful therapy for mothers and newborns? Can Fam Physician. 2005 Nov;51(11):1477-9.
• Background Morelli L, Zonenenschain D, Del Piano M, Cognein P. Utilization of the intestinal tract as a delivery system for urogenital probiotics. J Clin Gastroenterol. 2004 Jul;38(6 Suppl):S107-10. doi: 10.1097/01.mcg.0000128938.32835.98.
• Background Burton JP, Cadieux PA, Reid G. Improved understanding of the bacterial vaginal microbiota of women before and after probiotic instillation. Appl Environ Microbiol. 2003 Jan;69(1):97-101. doi: 10.1128/AEM.69.1.97-101.2003.
• Background Reid G, Beuerman D, Heinemann C, Bruce AW. Probiotic Lactobacillus dose required to restore and maintain a normal vaginal flora. FEMS Immunol Med Microbiol. 2001 Dec;32(1):37-41. doi: 10.1111/j.1574-695X.2001.tb00531.x.
• Background Bocking A. Probiotic therapy for the reversal of Bacterial Vaginosis in pregnancy (ProVIP). ClinicalTrials.gov [Internet]. Accessed January 2013. Available from: http://www.clinicaltrials.gov/ct2/show/NCT01697683?term=Bocking%2C+A&rank=10
• Background Reid G. Effects of probiotics on rheumatoid arthritis patients. ClinicalTrials.gov [Internet]. Accessed January 2013. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00664820?term=%22Canada%22+AND+%22Probiotics%22&rank=2

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