Use of probiotics to reduce infections and death and prevent colonization with extended-spectrum beta-lactamase (ESBL)- producing bacteria among newborn infants in Tanzania (ProRIDE Trial): study protocol for a randomized controlled clinical trial

Abstract

Abstract Background: Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) has emerged as an urgent global health threat and is by the World Health Organization ranked as priority 1 among pathogens in need of new treatment. Studies have shown high mortality in Tanzanian children with ESBL-E infections. Gut colonization of ESBL-E, which is a potential risk factor of ESBL-E infections, is reported to be very high among children in Tanzania. Probiotics may potentially reduce gut colonization of multidrug-resistant bacteria. However, there is limited data on whether probiotics may reduce ESBL-E carriage in infants. The ProRIDE Trial aims to evaluate whether the use of probiotics can reduce morbidity and mortality among infants in Haydom, Tanzania, and whether this effect is associated with a reduction in ESBL-E colonization and/or infections. Methods/design: This large randomized double-blinded placebo-controlled trial aims to recruit 2000 newborn infants at Haydom Lutheran Hospital and the surrounding area in the period of November 2020 to November 2021. Participants will be enrolled from days 0 to 3 after birth and randomized to receive probiotics or placebo for 4 weeks. Participants will be followed-up for 6 months, during which three visits will be made to collect clinical and demographic information, as well as rectal swabs and fecal samples which will be subjected to laboratory analysis. The primary composite outcome is the prevalence of death and/or hospitalization at 6 months of age Discussion: As the use of probiotics may give a more favorable gut composition, and thereby improve health and reduce morbidity and mortality, the results may have implications for future therapy guidelines in Africa and internationally. Trial registration: ClinicalTrials.gov NCT04172012. Registered on November 21, 2019 Keywords: Newborn, Infants, Probiotics, Gut colonization, Extended-spectrum beta-lactamase, ESBL, Enterobacteriaceae, Infant mortality, Hospitalization, Microbiota, Resistome, Randomized controlled trial