Incidence and predictive biomarkers of Clostridioides difficile infection in hospitalized patients receiving broad-spectrum antibiotics
Cornelis H. van Werkhoven, Annie Ducher, Matilda Berkell, Mohamed Mysara, Christine Lammens, Julián Torre‐Cisneros, Jesús Rodríguez‐Baño, Delia Herghea, Oliver A. Cornely, Lena M. Biehl, Louis Bernard, M.Á. Domínguez, Sofia Maraki, Olivier Barraud, Maria Nica, Nathalie Jazmati, Frédérique Sablier-Gallis, Jean de Gunzburg, France Mentré, Surbhi Malhotra‐Kumar, Marc J. M. Bonten, Maria J. G. T. Vehreschild, the ANTICIPATE Study Group, Annemarie M. S. Engbers, Marieke J. A. de Regt, Herman Goossens, Basil Britto Xavier, Marie-Noëlle Bouverne, Pieter Monsieurs, Uta Merle, Andreas Stallmach, Jan Rupp, Johannes R. Bogner, Christoph Lübbert, Gerda Silling, Oliver Witzke, Achilleas Gikas, George Daikos, Sotirios Tsiodras, Athanasios Skoutelis, Helen Sambatakou, Miquel Pujol, J. M. Aguado, Emilio Bouza, Javier Cobo, Benito Almirante, Simin Aysel Florescu, A Vâţă, Adriana Hristea, Mihaela Lupșe, D. Postil, Jean‐Michel Molina, Victoire de Lastours, Thomas Guimard, Jean‐Philippe Talarmin, Xavier Duval, Odile Launay
Abstract
Abstract Trial enrichment using gut microbiota derived biomarkers by high-risk individuals can improve the feasibility of randomized controlled trials for prevention of Clostridioides difficile infection (CDI). Here, we report in a prospective observational cohort study the incidence of CDI and assess potential clinical characteristics and biomarkers to predict CDI in 1,007 patients ≥ 50 years receiving newly initiated antibiotic treatment with penicillins plus a beta-lactamase inhibitor, 3 rd /4 th generation cephalosporins, carbapenems, fluoroquinolones or clindamycin from 34 European hospitals. The estimated 90-day cumulative incidences of a first CDI episode is 1.9% (95% CI 1.1-3.0). Carbapenem treatment (Hazard Ratio (95% CI): 5.3 (1.7-16.6)), toxigenic C. difficile rectal carriage (10.3 (3.2-33.1)), high intestinal abundance of Enterococcus spp. relative to Ruminococcus spp. (5.4 (2.1-18.7)), and low Shannon alpha diversity index as determined by 16 S rRNA gene profiling (9.7 (3.2-29.7)), but not normalized urinary 3-indoxyl sulfate levels, predicts an increased CDI risk.