Year: 2025
Type: article
Abstract: To the Editor—As developers of the encapsulated fecal microbiota formulation being tested, we read with interest and chagrin the report of the placebo-controlled clinical trial entitled “A Randomized Controlled Trial of Efficacy and Safety of Fecal Microbiota Transplanted for Preventing Recurrent Clostridioides difficile Infection” by Drekonja and colleagues [1]. We believe the paper underscores the importance of clinicians knowing the natural history of the disease and the pharmacology of the drug used to treat it. The pharmacokinetics of the encapsulated microbiota formulation used by Drekonja et al, outlined in our original 2017 publication, showed that optimal microbiome repair requires more than a week following discontinuing antibiotic therapy [2]. In a follow-up 2018 paper, we reported that poor engraftment of key bacterial taxa, including families Lachnospiraceae, Ruminococcaceae, and Bacteroidaceae, at 1 week after capsule fecal microbiota transplant (FMT) administration was predictive of treatment failure [3]. A 1-week delay in offering capsule FMT treatment following completion of the antibiotic course, as was done in this trial, would guarantee zero engraftment at 1 week and predict clinical failure in the following weeks. Prevention of C. difficile infection recurrence using live biotherapeutic products depends on rapid restoration of colonization resistance before C. difficile bacteria are allowed to mount a come-back and toxin production. The interval between the completion of antibiotic therapy and the administration of donor microbiota is a critical variable in achieving treatment success. Premature administration of donor microbiota risks poor engraftment due to residual antibiotics in the colon. Delayed administration of microbiota risks providing an early unopposed advantage to C. difficile bacteria. When used in accordance with our recommendations (2- to 3-day interval after completion of antibiotics), the described formulation achieves ∼85% cure rate of recurrent C. difficile infection in clinical practice [4]. Unfortunately, instead of trying to prevent C. difficile infection recurrence, as the title of this trial suggests, the investigators were attempting to treat the infection already in progress. The results are not surprising but are instructive. Financial support. A. K. and C. S. received no financial support for this contribution.
Source: Clinical Infectious Diseases
DOI: 10.1093/cid/ciaf138
Authors: Alexander Khoruts, Christopher Staley
Institution: University of Minnesota
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4409681675