Tacrolimus concentration to dose ratio in solid organ transplant patients treated with fecal microbiota transplantation for recurrent Clostridium difficile infection

• Type of Material: Article
• Authors: Michael Woodworth, Emory University; Colleen Kraft, Emory University; Erika J. Meredith, Emory University; Aneesh Mehta, Emory University; Tiffany Wang, Emory University; Yafet T. Mamo, Emory University; Tanvi Dhere, Emory University; Kaitlin L. Sitchenko, Emory University; Rachel Patzer, Emory University; Rachel Friedman-Moraco, Emory University
• Language: English
• Date: 2018-04-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
• Final Published Version (URL): http://dx.doi.org/10.1111/tid.12857
• Title of Journal or Parent Work: Transplant Infectious Disease
• ISSN: 1398-2273
• Volume: 20
• Issue: 2
• Start Page: e12857
• End Page: e12857
• Grant/Funding Information: Supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award number UL1TR000454.
• Keywords: Infectious Diseases; GUT MICROBIOTA; tacrolimus; RECIPIENTS; Life Sciences & Biomedicine; Science & Technology; Immunology; VERSUS-HOST-DISEASE; pharmacokinetics; Clostridium difficile; fecal microbiota transplantation; Transplantation
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Medicine and Surgery; Health Sciences, Pathology

Abstract

Fecal microbiota transplantation (FMT) is increasingly being performed for Clostridium difficile infection in solid organ transplant (SOT) patients; however, little is known about the potential pharmacokinetic or pharmacomicrobial effects this may have on tacrolimus levels. We reviewed the medical records of 10 SOT patients from September 2012-December 2016 who were taking tacrolimus at time of FMT for recurrent C. difficile infection. We compared the differences in tacrolimus concentration/dose ratio (C/D ratio) 3 months prior to FMT vs 3 months after FMT. The mean of the differences in C/D ratio calculated as (ng/mL)/(mg/kg/d) was −17.65 (95% CI −1.25 to 0.58) (ng/mL)/(mg/kg/d), P-value.43 by Wilcoxon signed-rank test. The mean of the differences in C/D ratio calculated as (ng/mL)/(mg/d) was −0.33 (95% CI −1.25 to 0.58) (ng/mL)/(mg/d), P-value.28 by Wilcoxon signed-rank test. Of these patients, 2/10 underwent allograft biopsy for allograft dysfunction in the year after FMT, with no evidence of allograft rejection on pathology. These preliminary data suggest that FMT may not predictably alter tacrolimus levels and support its safety for SOT patients however further study in randomized trials is needed.