Reply to Davido et al

To the Editor—We thank Davido et al for their comments on our report on the impact of fecal microbiota transplantation (FMT) on antimicrobial resistance gene acquisition and depletion among patients with recurrent Clostridium difficile infection (CDI) [1, 2]. We agree that inferences based on our small sample should be limited and additional, larger clinical studies are required to validate our observations. Davido et al raise 3 points. First, we confirm that no carbapenemase-encoding genes were identified in our cohort. Second, we agree that antibiotic administration prior to FMT may impact microbiota composition and antimicrobial resistance gene carriage. However, we reiterate that recipients of FMT in our study were given vancomycin until 2 days before FMT, and not “2 days prior to FMT” as Davido et al state in their letter. This means that fecal samples for our study were taken approximately 48 hours after the last dose of oral vancomycin. Resistance gene acquisition may occur via stool donation immediately following FMT, but may also appear to occur in recipients receiving antibiotic treatment just prior to FMT; differentiating between these 2 sources of resistance gene acquisition is challenging. Our data suggest that the potential for resistance gene acquisition as the result of FMT is an important consideration in using FMT therapy. This risk should be balanced against the potential benefits of the FMT procedure for preventing recurrent CDI and for multidrug-resistant organism (MDRO) decolonization. Third, it is interesting to note that depletion of clinically meaningful resistance genes occurred in almost all recipients, despite the inclusion of 8 unique donors. However, the degree of gene depletion varied by donor–recipient pair. For example, pairs 5 and 8 experienced the loss of many more resistance genes than the other pairs. Currently, the clinical evidence for FMT MDRO decolonization efficacy is still very limited, and there may be significant differences in efficacy by unrecognized host factors and by the bacterial species being targeted (eg, extended spectrum β-lactamase–producing Escherichia coli vs vancomycin-resistant enterococci). More intervention studies of FMT are needed to determine MDRO decolonization effectiveness, safety, durability, and mechanism of action in a wider spectrum of potential recipients. Potential conflicts of interest. A. R. M. has received research funding from a 2011 Pfizer Aspire Antibacterial Research Award. M. M. has been an employee of bioMérieux since October 2012. C. V. received a studentship from the Research Institute of the McGill University Health Centre, as well as a Frederick Banting and Charles Best Canada Graduate Scholarship (Doctoral Award) from the Canadian Institutes of Health Research (GSD-113375). C. V. also has been an employee of Roche Diagnostics since 2016. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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