Reviewed by Eric Lofgren, Washington State University
The potential risk of pathogen transmission during fecal microbiota transplantation (FMT) has been the reason potential donor stool is carefully screened. In this report, the authors detail two cases of ESBL-producing E. coli bacteremia (one of them fatal) in patients in two separate clinical trials that were linked to the same donor. Since January 2019 stool samples have been prospectively screened for ESBL-producing organisms; however; at the time of these cases samples were not screened, including the implicated donor samples which were produced in November 2018. The first case arose in a 69-year-old man enrolled in a trial using FMT oral capsules to treat refractory hepatic encephalopathy, who developed symptoms 17 days after the final FMT dose and stabilized after a course of antibiotics. The second patient was a 73-year-old man in a phase 2 trial of the preemptive administration of FMT oral capsules before and after allogeneic hematopoietic-cell transplant. He developed symptoms 8 days after the final FMT dose and died from severe sepsis two days later.
Fecal samples taken prior to FMT from both patients were negative for ESBL-producing organisms by culture. Genetic analysis revealed that ESBL-producing E. coli in the patients’ blood samples was closely related to the organisms in the donor stool sample. Alarmingly, 22 total patients received FMT capsules from this donor. For 12 tested patients in the clinical trials, 5 post-FMT samples grew ESBL-producing organisms, and for 7 tested patients being treated for recurrent or refractory C. difficile, 4 had post-FMT samples that grew ESBL-producing organisms. While these cannot be definitively linked to the donor, the high rate of ESBL positive cultures suggests future potential transmission from contaminated donor stool.
This report is an important cautionary tale. As the use of FMT for clinical trials in patients with extensive comorbidities, and on antibiotic treatments that may select for ESBL-producing organisms increases, screening donor stool for ESBL-producing organisms is essential to prevent the widespread dissemination of potentially deadly pathogens to trial participants.
DeFilipp, Z., P.P. Bloom, M.T. Soto, M.K. Mansour et al. (2019) Drug-Resistant E. coli Bacteremia Transmitted by Fecal Microbiota Transplantation. NEJM 381(21) pp 2043-50. https://www.ncbi.nlm.nih.gov/pubmed/31665575