REACTing Against Resistance: Fecal Microbiota Transplant Shows Safety and Promise in Long-Term Care Patients
Noor Syed, MD
Gastroenterology Fellow, Division of Gastroenterology and Hepatology, University of Michigan Ann Arbor, MI
This article reviews Woodworth MH, Babiker A, Prakash-Asrani R, et al. Microbiota Transplantation Among Patients Receiving Long-Term Care: The Sentinel REACT Nonrandomized Clinical Trial. JAMA Netw Open. 2025;8(7):e2522740.
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Correspondence to Noor Syed, Associate Editor. Email: EBGI@gi.org
Keywords: Fecal microbiota transplantation (FMT), multidrug-resistant organisms (MDROs), gut microbiome
STRUCTURED ABSTRACT
Question: Among long-term acute care hospital (LTACH) patients colonized with multidrug-resistant organisms (MDROs), is fecal microbiota transplantation (FMT) superior to no treatment (contemporaneous controls) for safety and infection-related outcomes?
Design: Single-center, open-label, nonrandomized pilot clinical trial with contemporaneous untreated controls; enrollment April–December 2023; follow-up 6 months.
Setting: Academic-affiliated LTACH in Atlanta, Georgia (Southeastern US); median ~50-patient census and ~28-day length of stay.
Patients: Participants were adults aged ≥18 years whom had a perirectal or stool culture positive for a target MDRO (extended-spectrum β-lactamase [ESBL] Enterobacterales, carbapenem-resistant Enterobacterales [CRE], multidrug-resistant [MDR] Pseudomonas, vancomycin-resistant Enterococcus [VRE], or toxigenic Clostridioides difficile); able/willing to receive FMT via feeding tube or retention enema; willing to discontinue antibiotics, probiotics/other microbiota therapies, and proton pump inhibitors (PPIs) ≥1 day before FMT through Day 28. Participants were excluded if: pregnant or breastfeeding, had a compromised immune system (e.g., AIDS with CD4<200 and detectable HIV load, ANC<1000, recent intensive chemo/radiotherapy or hematopoietic cell transplant) or had an inability to discontinue PPI therapy.
Interventions: Healthy-donor fecal microbiota (50–100 g stool suspended in 250 mL normal saline with 9% glycerol) instilled via gastrostomy tube or enema; no antibiotic or bowel-prep conditioning.
Outcomes: Primary: frequency and severity of adverse events (AEs) graded by CTCAE v5.0; solicited AEs assessed daily through Day 7; unsolicited AEs through 6 months. Secondary: proportion MDRO-positive perirectal/stool cultures at Weeks 2 and 4 after FMT. MDROs included ESBL Enterobacterales, CRE, MDR Pseudomonas, VRE, and toxigenic C. difficile. Exploratory: bloodstream infection, intestinal pathogen dominance by metagenomics, antibiotic days of therapy, and healthcare utilization over the 6 months before vs after prevalence sampling.
Data Analysis: Descriptive summaries; Wilcoxon rank-sum for continuous variables; Fisher exact for proportions; 2-sided α=0.05. Difference-in-differences model for antibiotic days of therapy; analyses in R. (Trial not powered for formal hypothesis testing.)
Funding: Emory Prevention Epicenter Program (CDC U54CK000601) and NIAID (K23AI144036, R38AI174306-01). Funders had no role in design, conduct, or analysis.
Results: Among 42 patients assessed (mean age ~64 years; 52% female overall), 10 received FMT and 32 served as contemporaneous MDRO-colonized controls. Routes among FMT recipients: 5 gastrostomy, 4 enema, 1 both (>30 days apart). No serious AEs were attributed to FMT; solicited post-FMT AEs were mild. At the final visit, all FMT recipients remained MDRO culture–positive. Post hoc comparisons (underpowered) showed numerically fewer FMT recipients with positive blood cultures in the following 6 months (0/10 vs 6/32 [19%]; P=0.31), lower pathogen intestinal dominance (25% vs 50%; P=0.61), and fewer antibiotic days of therapy (median 12.6 vs 19.7 days per 1000 patient-days; P=0.38); a difference-in-differences analysis estimated 26 fewer antibiotic days per 1000 patient-days (95% CI, −64 to 12) after FMT.
Bottom line: In LTACH patients with MDRO colonization, single-dose FMT (via gastrostomy or enema) was acceptable and not associated with related serious adverse events (AEs); signals toward reduced bacteremia and antibiotic use did not reach statistical significance and warrant testing in larger randomized trials (Table 1).
| Outcome | FMT Group (n=10) | Control Group (n=32) | P value | Interpretation |
| Serious adverse events related to FMT | 0 | — | — | No FMT-related serious AEs reported |
| Any adverse event (solicited, ≤7 days) | Mild, transient GI symptoms only | — |
— |
FMT well tolderated |
| MDRO colonization at final visit | 10/10 (100%) | 32/32 (100%) | — | Persistent MDRO colonization in all participants |
| Bloodstream infection within 6 mo | 0 / 10 (0%) | 6/32 (19%) | 0.31 | Trend toward fewer BSIs after FMT |
| Pathogen intestinal dominance* | 25% | 50% | 0.61 | Numerically lower in FMT group |
| Antibiotic DOT per 1,000 patient-days | 12.6 | 19.7 | 0.38 | Fewer antibiotic DOTs post-FMT |
| Difference-in-differences: DOT change (95% CI) | −26 days (−64 to +12) | Reference | — | Suggests reduced antibiotic exposure after FMT |
Table 1. Clinical and microbiologic outcomes in the REACT trial comparing fecal microbiota transplantation (FMT) with contemporaneous controls among long-term acute care patients colonized with multidrug-resistant organisms (MDROs). FMT was well tolerated with no related serious adverse events and showed numerical reductions in bloodstream infections and antibiotic use, though not statistically significant. BSI, bloodstream infection; CI, confidence interval; DOT, days of therapy; GI, gastrointestinal.
*Dominance defined by metagenomic relative abundance > 30% of any MDRO species in stool.
COMMENTARY
Why Is This Important?
Multidrug-resistant organism (MDRO) colonization among long-term acute care hospital (LTACH) patients poses a major infection-control and antimicrobial stewardship challenge. These patients often have prolonged hospital stays, frequent antibiotic exposure, and high risks for bacteremia and mortality. Current decolonization strategies are largely ineffective or transient. Fecal microbiota transplantation (FMT) has shown promise in restoring microbial diversity and suppressing pathogen dominance, but data in frail, long-term care populations are limited. This study provides early safety and feasibility data for FMT in this high-risk setting and explores whether microbiota restoration can reduce MDRO colonization and infection burden.
Key Study Findings
Among 42 LTACH patients colonized with MDROs (10 FMT recipients, 32 controls), no serious adverse events were attributed to FMT. Solicited adverse events were mild and transient. At final follow-up, all participants remained MDRO culture–positive. However, FMT recipients had numerically fewer bloodstream infections (0% vs 19%), lower intestinal pathogen dominance (25% vs 50%), and fewer antibiotic days of therapy (12.6 vs 19.7 per 1000 patient-days). The difference-in-differences analysis estimated 26 fewer antibiotic days per 1000 patient-days (95% CI, −64 to 12) among FMT recipients.
Caution
This was a single-center, open-label, nonrandomized pilot trial with a small sample size, limiting statistical power and generalizability. The lack of randomization introduces potential selection bias, and persistent MDRO colonization at follow-up suggests that a single FMT dose may be insufficient. The authors also noted that unmeasured confounders (such as antibiotic exposure and comorbidities) could influence results. Additionally, findings may not extend to acute-care or community settings, given the frailty and complexity of the LTACH population.
My Practice
As a current gastroenterology fellow, I do not yet maintain an independent clinical practice, but I see clear potential for FMT as an adjunctive tool in managing MDRO colonization among long-term care patients and potentially even in an acute care setting. This study reinforces its safety in a vulnerable cohort and aligns with growing interest in microbiota-based therapies to limit antimicrobial resistance and recurrent infection. I anticipate that, as evidence matures, FMT or next-generation microbiota products will increasingly be integrated into infection-prevention strategies.
For Future Research
A multicenter, randomized controlled trial with a larger sample size comparing standardized FMT (or microbiota-based live biotherapeutic products) versus placebo or usual care is needed to confirm efficacy in reducing MDRO colonization, bloodstream infections, and antibiotic utilization. Future studies should also evaluate optimal dosing schedules, routes of delivery, and effects on microbiome restoration and transmission dynamics within LTACH and nursing facility networks.
Conflict of Interest
The author reports no potential conflicts of interest related to this study.
REFERENCES
- Woodworth MH, Babiker A, Prakash-Asrani R, et al. Microbiota transplantation among patients receiving long-term care: The Sentinel REACT Nonrandomized Clinical Trial. JAMA Netw Open. 2025;8(7):e2522740. doi:10.1001/jamanetworkopen.2025.22740.
- Woodworth MH, Hayden MK, Donskey CJ, Bonten MJM, van Duin D. Fecal microbiota transplantation for multidrug-resistant organism decolonization: A review and practical guide. Clin Infect Dis. 2019;68(12):2125–2131. doi:10.1093/cid/ciy822.
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