Microbiota-associated Risk Factors for Clostridioides difficile Acquisition in Hospitalized Patients: A Prospective, Multicentric Study. (26th June 2020)

• Record Type: Journal Article
• Authors: Solbach, Philipp; Chhatwal, Patrick; Woltemate, Sabrina; Tacconelli, Evelina; Buhl, Michael; Autenrieth, Ingo B; Vehreschild, Maria J G T; Jazmati, Nathalie; Gerhard, Markus; Stein-Thoeringer, Christoph K; Rupp, Jan; Ulm, Kurt; Ott, Armin; Lasch, Florian; Koch, Armin; Manns, Michael P; Suerbaum, Sebastian; Bachmann, Oliver
• Is Part Of: Clinical infectious diseases. Volume 73:Number 9(2021)
• Page Start: e2625
• Page End: e2634
• Publication Date: 2020-06-26
• Subjects: toxigenic -- difficile -- Gemmiger spp -- bile acids -- microbiota; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciaa871
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract: Background: Asymptomatic C. difficile colonization is believed to predispose to subsequent C. difficile infection (CDI). While emerging insights into the role of the commensal microbiota in mediating colonization resistance against C. difficile have associated CDI with specific microbial components, corresponding prospectively collected data on colonization with C. difficile are largely unavailable. Methods: C. difficile status was assessed by GDH EIA and real-time PCR targeting the toxin A (tcdA) and B (tcdB) genes. 16S V3 and V4 gene sequencing results from fecal samples of patients tested positive for C. difficile were analyzed by assessing alpha and beta diversity, LefSe, and the Piphillin functional inference approach to estimate functional capacity. Results: 1506 patients were recruited into a prospective observational study (DRKS00005335) upon admission into one of five academic hospitals. 936 of them provided fecal samples on admission and at discharge and were thus available for longitudinal analysis. Upon hospital admission, 5.5% (83/1506) and 3.7% (56/1506) of patients were colonized with toxigenic (TCD) and non-toxigenic C. difficile (NTCD), respectively. During hospitalization, 1.7% (16/936) acquired TCD. Risk factors for acquisition of TCD included pre-existing lung diseases, lower GI endoscopy and antibiotics. Species protecting against hospital-related C. difficile acquisition included Gemmiger spp., Odoribacter splanchnicus, Ruminococcus bromii and other Ruminococcus spp. Metagenomic pathway analysis identified steroid biosynthesis as the most underrepresented metabolic pathway in patients who later acquire C. difficile colonization. Conclusions: Gemmiger spp., Odoribacter splanchnicus, Ruminococcus bromii and other Ruminococci were associated with a decreased risk of C. difficile acquisition. Clinical Trials Registration: DRKS00005335. Abstract : In this prospective, multicentric study Gemmiger spp., Odoribacter splanchnicus, Ruminococcus bromii, and other Ruminococcus spp. could be identified as biomarkers for hospital-acquired C. difficile colonization. In silico metagenomics showed metabolic pathways for steroid biosynthesis to be protective against C. difficile.