AMR strategies in LMIC newborns reduce antibiotic use and mortality in meta-analysis

BACKGROUND: Optimal strategies to reduce antimicrobial resistance (AMR) and their effect on newborns in low-income and middle-income countries (LMICs) remain unclear. We assessed the effectiveness of AMR mitigation strategies for newborn care in LMICs. METHODS: A systematic review and meta-analysis was conducted. We searched MEDLINE, Embase, CINAHL, Global Index Medicus, Cochrane Central Register of Controlled Trials, and grey literature from Jan 1, 2000, to Nov 20, 2025, for randomised or quasi-randomised trials, quasi-experimental studies, observational or implementation studies, and programme evaluations. We included studies comparing any intervention, policy, or strategy designed to mitigate AMR development and spread (intervention) among newborns receiving facility-based or community-based care in LMICs (population), with standard practices or no intervention (comparator), on a range of outcomes including clinical and antibiotic use outcomes (outcome). Strategies to reduce AMR were categorised as regulation (structural or organisational actions), education (health-care worker trainings), or optimisation (responsible antimicrobial use). We pooled data from included studies to estimate the effectiveness of each of the three strategy types or a combination thereof. Given the low-resource context, we also narratively synthesised the available evidence on barriers and facilitators to implementing strategies to reduce AMR in newborn care settings (PROSPERO CRD42023388338). FINDINGS: Of 3688 studies screened, 31 facility-based studies were included. Regulation reduced the risk of newborns receiving at least one antimicrobial by 21% (risk ratio 0·79 [95% CI 0·77-0·80]), but had no effect on neonatal sepsis risk. Optimisation reduced culture-positive sepsis risk by 32% (0·68 [0·55-0·83]) and risk of newborns on antibiotics by 13% (0·87 [0·78-0·98]), but had no effect on neonatal mortality risk. Regulation and optimisation did not significantly reduce neonatal mortality due to nosocomial bloodstream infection (BSI) risk (0·62 [0·31-1·25]). Regulation, education, and optimisation reduced neonatal mortality risk by 27% (0·73 [0·57-0·93]) and multidrug-resistant organism infections or colonisation risk by 29% (0·71 [0·52-0·97]). Regulation, education, and optimisation also decreased the risk of newborns receiving antibiotics by 29% (0·71 [0·61-0·81]) and the risk of duration of antibiotic therapy exceeding 5 days by 64% (0·36 [0·14-0·93]). Effect direction plots revealed overall positive directions of effect for outcomes including neonatal mortality (72·72%), neonatal mortality due to nosocomial BSI (100%), sepsis (75%), and drug-resistant (100%) and multidrug-resistant (80%) infection and colonisation. Effect direction plots also showed decreased overall antibiotic use (94·7%), access (71·4%) and watch (88·9%) antibiotic use, and duration of antibiotic therapy (83·3%) after strategies to reduce AMR were implemented. Common implementation barriers included delays in reporting culture test results, health-care worker non-adherence to infection prevention and control measures, and challenges in antibiotic prescribing for culture-negative newborns with sepsis-like presentation. INTERPRETATION: To improve clinical outcomes, interventions targeting the control of antimicrobials alone will not suffice. Our results showed that three types of interventions (regulation, education, and optimisation) must be taken together to reduce AMR. These results can inform and accelerate guidance development for multi-dimensional, holistic, and integrated maternal and newborn care programmes in LMICs. FUNDING: The Bill & Melinda Gates Foundation.