Can Fecal Microbiota Transplantation (FMT) Eradicate Fecal Colonization With Vancomycin-Resistant Enterococci (VRE)?

To the Editor—Recently, fecal microbiota transplantation (FMT) has been attempted to eliminate colonization with multidrug-resistant organisms (MDROs), and case reports have shown considerable success. ¹ In addition, FMT was effective for reducing antibiotic resistant genes in patients with recurrent Clostridium difficile infection (CDI), ² which may have a significant role in MDRO decolonization. However, publication bias could exist against studies with negative findings for MDRO decolonization, and clinical evidence for extending the application of FMT remains sparse. We performed FMT to eradicate long-term vancomycin-resistant enterococci (VRE) colonization in 3 patients. Prolonged VRE colonization was documented by repeated rectal swab cultures (positive VRE on at least 4 consecutive swabs taken 1 week apart). Of these 3 patients, 2 had recurrent CDI and were treated with oral metronidazole and vancomycin (Table 1, cases 1 and 2). Another patient (case 3) remained in the hospital for isolation purposes due to VRE carriage after completion of treatment. Vancomycin resistance was confirmed using chromogenic agar and polymerase chain reaction. All cases were Enterococcus faecium with the vanA gene. Voluntary informed consent was obtained for FMT. Stools were donated by the patient’s granddaughter (case 1, 18 years old), daughter (case 2, 45 years old), and son (case 3, 50 years old), respectively. The donors were healthy and no problems were identified on pre-donation screening tests; they were all negative for stool VRE. Oral vancomycin treatment was discontinued on the day before FMT (case 1 and 2), and the donor stool (100 g) in normal saline (200 mL) was transplanted to the patient via retention enema after environmental disinfection. All patients were able to retain the infusate for at least 1 hour, and there were no adverse events. In case 3, a second FMT was performed 1 day after the first FMT. All antibiotics were stopped after the FMT was conducted except in case 2, in which the patient developed pneumonia 15 days after FMT and piperacillin-tazobactam was given for 2 weeks. Patient characteristics and outcomes are summarized in Table 1. Patients 1 and 2 experienced resolution of CDI symptoms without recurrence during admission. After transferring to other facilities, 2 patients were lost to follow-up. We did not recruit additional patients because FMT did not shorten the duration of VRE carriage in these 3 patients.

TABLE 1 Clinical Characteristics and Outcomes of Patients with Vancomycin-Resistant Enterococci Colonization Who Underwent Fecal Microbiota Transplantation

NOTE. FMT, fecal microbiota transplantation; CDI, Clostridium difficile infection; HTN, hypertension; DM, diabetes mellitus; RA, rheumatoid arthritis; VRE, vancomycin-resistant enterococci.

^a Patient 1 was discharged from the hospital 1 month after FMT. She cleared VRE colonization 15 weeks after FMT (3 consecutive negative VRE cultures a minimum of 1 week apart at the outpatient clinic).

^b Patent 2 was transferred to a long-term care facility 10 weeks after FMT and was lost to follow-up.

^c Patient 2 developed pneumonia 15 days after FMT, and piperacillin-tazobactam was given for 2 weeks.

^d Patient 3 was transferred to a long-term care facility 21 weeks after FMT and no further rectal VRE cultures were performed.

Our data are supported by the Jang et al ³ case report in which FMT was performed twice to control refractory CDI. Their patient was also colonized with VRE and, despite resolution of CDI, rectal VRE carriage persisted for at least 3 months. Although we used the lower delivery route (enema), Jang et al transplanted stool via both enema and the upper route (nasoduodenal tube). ³

Ubeda et al ⁴ showed that reintroduction of a diverse intestinal microbiota to heavily VRE-colonized mice could eliminate VRE from the gut. Specifically, the presence of Barnesiella species in the intestinal tract was able to confer resistance to VRE in patients undergoing allogeneic hematopoietic stem cell transplantation. ⁴ Stielfel et al ⁵ reported that cephalosporinase-producing Bacteroides thetaiotaomicron prevented overgrowth of VRE and C. difficile in cephalosporin-treated mice. Defined microbiota transplant instead of whole stool may lead to more successful outcomes. Although these data are promising, it is not clear whether single bacterial species transfers would work in the human gastrointestinal tract.

In an industry-sponsored trial using an experimental microbiota suspension, 8 of 11 patients (73%) became VRE negative 1–6 months following FMT by enema. ⁶ However, the patients could have experienced spontaneous eradication. Because clearance of VRE varies widely, occurring after a median time of <3 months after discharge from the hospital without FMT and 6.5 months after antibiotics that promote VRE are discontinued, ^{7 , 8} it remains unclear whether FMT reduces the duration of VRE colonization.

Although FMT may contribute to shrinkage of the gut resistome, it does not seem to effectively shorten the duration of VRE carriage and may not be justified for the clearance of fecal colonization with VRE. Ongoing clinical trials will help resolve this issue and should help identify more effective methods of FMT against VRE colonization.