Gabriel Perreault, MD, MS1, Jessica Baylor, BS2, Arielle Radin, BS3, Norman Javitt, MD, PhD1, Lea Ann Chen, MD1
1New York University School of Medicine, New York, NY; 2Geisinger Health System, New York, NY; 3University of California Los Angeles, Los Angeles, CA
Introduction: Fecal microbiota transplant (FMT) is an effective treatment for recurrent Clostridioides difficile infection (rCDI), but its precise mechanism remains unknown (1-2). Recent studies suggest that the restoration of gut bacteria, which carry necessary enzymes to convert primary bile acids (PBAs) to secondary bile acids (SBAs), may play a key role in rCDI risk (3, Fig 1). For example, in vitro studies have demonstrated that PBAs stimulate C. difficile spore germination and that deoxycholic acid, a SBA, inhibits toxin-producing C. difficile (4). As normal fecal bile acid pools consist predominantly of SBAs, we hypothesize that a contributor of rCDI risk is the decrease in SBAs from enteric bacteria loss following antibiotic use (5-8). We present the first case enrolled in our clinical trial using ursodeoxycholic acid (UDCA), a SBA, as an adjunct treatment to prevent future rCDI.
Case Description/Methods: An otherwise healthy 46-year-old man presented with S. aureus bacteremia secondary to septic knee arthritis. While on an extended course of cefazolin, he developed profuse, watery diarrhea and stool C. difficile toxin PCR was positive. He was then treated with intravenous metronidazole for one week and oral vancomycin for two weeks, with resolution of symptoms. Six weeks later, CDI recurred and was successfully treated with oral vancomycin for two weeks, in conjunction with concurrent UDCA 300 mg twice daily for eight weeks. Stool samples were collected at two-week intervals and fecal bile acid compositions were assessed via liquid chromatography - mass spectrometry. Fecal bile acid analyses demonstrated a shift towards protective SBAs by the end of the 8-week course of ursodiol (Fig 2). This profile of increased SBAs remained consistent despite subsequent retreatment with cefazolin at 5 months for recurrent septic arthritis. The patient has been without rCDI now for almost 2 years.
Discussion: The findings in this case are consistent with our hypothesis that increasing SBAs through adjunct treatment with UDCA can be effective in breaking the rCDI cycle. While some CDI patients have adequate enteric bacteria to produce SBAs after antibiotic treatment, others may have a delayed normalization of their gut microbiome, and may therefore require “bridge therapy” with supplementary SBAs (e.g. UDCA) until their endogenous microbial community is restored. Treatment and analysis of additional patients with rCDI in this clinical trial are in progress.
Citation: Gabriel Perreault, MD, MS; Jessica Baylor, BS; Arielle Radin, BS; Norman Javitt, MD, PhD; Lea Ann Chen, MD. P0176 - URSODEOXYCHOLIC ACID FOR THE MANAGEMENT OF RECURRENT CLOSTRIDIOIDES DIFFICILE INFECTION. Program No. P0176. ACG 2019 Annual Scientific Meeting Abstracts. San Antonio, Texas: American College of Gastroenterology.