Abstract
BACKGROUND: Inappropriate antibiotic use is a key driver of antimicrobial resistance (AMR), a growing global threat that disproportionately affects children in low and lower-middle-income countries (LLMICs). In response, the WHO Global Research Agenda for Antimicrobial Resistance in Human Health prioritises research on antimicrobial stewardship programs (ASPs, formally introduced in 2007) and feasible point-of-care testing (POCT) in paediatric populations, where evidence on implementation and effectiveness remains limited. We aimed to address this gap and inform the design and scale-up of paediatric-focused strategies via a systematic review and meta-analysis on the impact of ASPs and POCTs in children in LLMICs. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, Cochrane Library, Scopus, Global Health, CINAHL, African Journals Online (AJOL), and Latin American and Caribbean Health Sciences Literature (LILACS) for relevant studies published between January 1, 2007, and December 31, 2024. A search update was conducted on September 1, 2025. The search strategy included a combination of Medical Subject Heading (MeSH) and free text terms for 'children', 'antibiotic', 'stewardship program', and 'point-of-care', without any language restrictions. Eligible studies included children (aged <18 years) and were conducted in healthcare settings (inpatient or outpatient) within LLMICs, as per 2024 World Bank classification. Randomised controlled trials, before-and-after, and cohort studies were eligible for inclusion. Outcomes were antibiotic use, guideline adherence, costs, antimicrobial resistance, and clinical outcomes. When three or more reports assessed the same intervention and outcome, a random-effects meta-analysis was performed, and odds ratios (ORs) with 95% confidence intervals (CIs) were reported. This work is registered with PROSPERO, CRD42024491248. FINDINGS: Of the 11,191 records identified, 78 reports from 13 countries in Africa and 12 countries in Asia were included in the evidence synthesis. These studies evaluated 68 ASPs and 30 POCTs, either alone or in combination. Most reported improvements in antibiotic prescribing (77%) and adherence to guidelines (80%). Success rates were higher when ASPs were combined with POCTs (85%) compared to ASPs (73%) or POCTs alone (80%). Bundled interventions were more effective (81%) than single ones (70%). No increase in adverse clinical outcomes was observed, supporting the safety of ASPs. Meta-analysis showed that clinical decision support systems reduced antibiotic prescribing in primary care (overall OR 0.17, 95% CI 0.07-0.45, I(2) 99.7). INTERPRETATION: Evidence shows that ASPs and POCTs are feasible and effective in children in LLMICs, supporting the development of adaptable, paediatric-focused strategies. Future research should focus on large-scale implementation studies and context-specific evaluations to optimise paediatric ASPs and POCTs in LLMICs. FUNDING: This work was conducted as part of the INF-ACT-One Health Basic and Translational Research Actions addressing Unmet Needs on Emerging Infectious Diseases, supported by the Italian National Recovery and Resilience Plan (NRRP, Mission 4, Component 2).