Fecal microbiota transplantation for intestinal decolonization of multidrug-resistant organisms: a systematic review, meta-analysis, and GRADE assessment of randomized controlled trials

Gut colonization by multidrug-resistant organisms (MDROs) is an important reservoir for subsequent infection and transmission. Fecal microbiota transplantation (FMT) is a plausible non-antibiotic decolonization strategy, but much of the supportive literature is uncontrolled and vulnerable to spontaneous-decolonization bias. We performed a PRISMA 2020 systematic review and meta-analysis of randomized controlled trials evaluating FMT or FMT-based regimens for intestinal MDRO decolonization (PROSPERO CRD420261428009). Cochrane Library, PubMed, Embase, and Scopus were searched from inception to 18 June 2026. The primary outcome was trial-defined microbiological decolonization at the closest assessment between 28 and 48 days. Risk ratios (RRs) were synthesized using random-effects models. Subgroup, leave-one-out, and small-sample analyses were exploratory. RoB 2 and GRADE were used for risk-of-bias and certainty assessment. Four RCTs contributed 202 participants to the primary analysis. FMT/FMT-based regimens did not show a statistically clear short-term decolonization benefit (RR 1.21, 95% CI 0.79–1.85; p = 0.39; I2 = 0%); with only four trials, I2 = 0% was not interpreted as clinical homogeneity. A conservative small-sample sensitivity analysis gave RR 1.21 (95% CI 0.60–2.42). Subsequent antibiotic use was highly uncertain (2 trials; RR 1.43, 95% CI 0.56–3.66). Diarrhea was more frequent in some intervention arms, but ascertainment and co-interventions differed substantially; the exploratory pooled estimate (RR 2.66, 95% CI 1.17–6.06) was not robust to small-sample or leave-one-out sensitivity analyses. Serious/severe adverse events were too heterogeneously defined for reliable pooling. Randomized evidence is insufficient to establish a clinically reliable benefit of FMT for short-term intestinal MDRO decolonization. The effect estimate remains compatible with benefit and no effect, while safety evidence is very uncertain. Larger trials should use standardized microbiological definitions, durable follow-up, and clinically meaningful endpoints. CRD420261428009. This review isolates randomized controlled evidence from earlier uncontrolled FMT literature, in which spontaneous MDRO decolonization can inflate apparent efficacy. Across four randomized trials, the short-term decolonization effect remained uncertain (RR 1.21, 95% CI 0.79–1.85); the confidence interval is compatible with clinically meaningful benefit as well as no effect. Safety findings require cautious interpretation: diarrhea ascertainment and co-interventions differed substantially across trials, and serious/severe adverse-event definitions were not sufficiently comparable for a reliable pooled estimate. The review incorporates the 2025 FERARO feasibility trial and the 2026 sham-controlled trial and provides trial-level outcome definitions, intervention/pre-conditioning details, transparent extraction data, RoB 2, GRADE, and sensitivity analyses.