2578. Narrow-Spectrum Antibiotic Treatment of Clostridium difficile Infection Improves Preservation of Intestinal Metabolic Profile

Abstract

BackgroundCommensal gut bacteria are thought to protect against C. difficile infection (CDI) by producing metabolites that inhibit C. difficile germination and growth. Alternatively, the protective effect could reflect nutrient competition or other mechanisms of chemical communication that also involve the host. CDI treatment using a broad-spectrum antibiotic such as vancomycin (VAN) dramatically depletes commensal bacteria. This dysbiosis can persist for several weeks after end-of-therapy (EOT), and is associated with increased recurrence risk. In this study, we investigate the hypothesis that treating CDI with a more selective antibiotic reduces collateral damage to the intestinal microbiota, preserving or restoring a CDI-inhibitory metabolic profile.MethodsStool samples were collected from CDI patients treated with either a narrow- (RDZ) or broad-spectrum antibiotic (VAN) at days 1, 10 (EOT), 25, and 40. Global metabolite profiles were measured by untargeted LC-MS.ResultsUntargeted metabolite analysis showed broad differences in the metabolic activity of intestinal microbiota of RDZ- and VAN-treated subjects (Figure 1). At EOT, 28% of LC-MS features detected in both RDZ and VAN samples were differentially present (FDR corrected P-value <0.05). Over 80% of the differentially present features were elevated in the RDZ group, indicating diminished capacity of microbiota from VAN subjects to generate diverse metabolic products. Pathway analysis found significant differences in purine, taurine, tyrosine, and bile acid metabolites. The VAN group showed a 5-fold decrease in free taurine, a major conjugation substrate of primary bile acids released by bacterial bile salt hydrolases. VAN treatment also decreased fermentation products of aromatic amino acids and amino sugars derived from mucin degradation. Oligosaccharides were the major metabolite class elevated in VAN subjects.ConclusionOur data suggest that RDZ treatment correlates with enhanced preservation of bacteria-derived ligands regulating intestinal immune function and substrates of bacterial metabolism. These metabolic profile differences between a narrow- and broad-spectrum antibiotic may contribute to their varying efficacy in preventing CDI recurrence. Disclosures All authors: No reported disclosures.