The Impact of Antimicrobial Stewardship in Children in Low- and Middle-income Countries A Systematic Review

Background: Antimicrobial stewardship (AMS) is central to the World Health Organisation Global Action Plan against antimicrobial resistance (AMR). If antibiotics are used without restraint, morbidity and mortality from AMR will continue to increase. In resource-rich settings, AMS can safely reduce antibiotic consumption. However, for children in low- and middle-income countries (LMIC), the impact of different AMS interventions is unknown. Aim: To determine the impact of different AMS interventions on antibiotic use and clinical and microbiologic outcomes in children in LMIC. Methods: MEDLINE, Embase and PubMed were searched for studies of AMS interventions in pediatric population in LMIC settings. Controlled trials, controlled before-and-after studies and interrupted time series studies were included. Outcomes assessed were antibiotic use, multidrug-resistant organism (MDRO) rates, clinical outcomes and cost. Results: Of 1462 studies, 34 met inclusion criteria including a total population of >5,000,000 in 17 countries. Twenty were in inpatients, 2 in ED, 10 in OPD and 2 in both. Seven studies were randomized controlled trials. All types of interventions reported a positive impact on antibiotic prescribing. AMS bundles with education, and clinical decision tools appeared more effective than guidelines alone. AMS interventions resulted in significantly decreased clinical infections (4/4 studies) and clinical failure (2/2) and reduced MDRO colonization rate (4/4). There was no concomitant increase in mortality (4/4 studies) or length of stay (2/2). Conclusion: Multiple effective strategies exist to reduce antibiotic consumption in LMIC. However, marked heterogeneity limit conclusions regarding the most effective approach, particularly regarding clinical outcomes. Overall, AMS strategies are important tools in the reduction of MDRO-related morbidity in children in LMIC.