Interventions targeting gut colonization by multi-drug-resistant organisms in healthcare settings: a systematic review and meta-analysis of randomized controlled trials.

Gut colonization with multi-drug-resistant organisms (MDROs) increases risks of infection, transmission and mortality in healthcare settings. Although decolonization strategies have been attempted to reduce the impact of gut MDROs, no consensus exists on their effectiveness. Our study evaluates the effectiveness of these strategies. We searched PubMed, Embase, CENTRAL, CINAHL and Web of Science for randomized controlled trials (RCTs) published from January 2005 to December 2024. Eligible studies included patients in healthcare settings with baseline MDRO colonization confirmed by rectal swab or stool sample. The primary outcome was reduction in colonization rates in the short term (<28 days) and long term (≥28 days). Two reviewers independently screened studies, extracted data and assessed bias using the Cochrane RoB 2 tool. A random-effects model was used for meta-analysis. This study was registered on PROSPERO (CRD42025625291). Of 900 studies screened, 14 RCTs were included. Interventions included probiotics (N = 7), oral non-absorbable antibiotics (N = 6) and fecal microbiota transplantation (FMT) with antibiotics (N = 1). No significant effect was observed for short-term (risk ratio [RR] = 1.18; 95% confidence interval [CI]: 0.81-1.71; P = 0.39) and long-term decolonization (RR = 1.12; 95% CI: 0.95-1.32; P = 0.16). Post-hoc subgroup analyses showed no significant differences across immune status, target organisms, intervention types and timing of outcome assessment. Risk of bias was low in four studies, with seven having some concerns and three at high risk. Certainty of evidence was low. Current evidence does not support routine use of interventions for gut MDRO decolonization. Well-powered RCTs focused on pathogen-specific interventions and clinically meaningful endpoints are needed to evaluate promising strategies for sustained decolonization (e.g. FMT) and emerging strategies (e.g. bacteriophages).