Incidence and predictive biomarkers of Clostridioides difficile infection in hospitalized patients receiving broad-spectrum antibiotics
the ANTICIPATE study group
(2021) Nature Communications, volume 12, issue 1, pp. 1 - 10
(Article)
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
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patients ≥ 50 years receiving newly initiated antibiotic treatment with penicillins plus a beta-lactamase inhibitor, 3rd/4th 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.
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Keywords: General Chemistry, General Biochemistry,Genetics and Molecular Biology, General Physics and Astronomy
ISSN: 2041-1723
Publisher: Nature Publishing Group
Note: Funding Information: This research project was supported by the Innovative Medicines Initiative Joint Undertaking (IMI JU) under grant agreement No. 115523, the Combatting Bacterial Resistance in Europe (COMBACTE) consortium, resources of which are composed of financial contribution from the European Union Seventh Framework Program (FP7/2007–2013) and Da Volterra, as a member of the European Federation of Pharmaceutical Industries and Associations (EFPIA) companies in kind and cash contribution. We thank Prof. Amee Manges (University of British Columbia, Vancouver, Canada) for providing the validation dataset utilized in this study. Funding Information: C.Hv.W. received speaker fees from Pfizer and Merck/MSD, and non-financial research support from bioMérieux. A.D. and F.S. are employees and shareholders of Da Volterra, Paris. J.G. is a consultant and shareholder of Da Volterra. J.T.C. has received speaker and consultant fess from Pfizer, MSD, Shionogy, Menarini and research support from Pfizer. O.A.C. is supported by the German Federal Ministry of Research and Education, is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy—CECAD, EXC 2030—390661388 and has received research grants from Actelion, Amplyx, Astellas, Basilea, Cidara, Da Volterra, F2G, Gilead, Janssen, Medicines Company, Melinta, Merck/MSD, Octapharma, Pfizer, Scy-nexis, is a consultant to Actelion, Allecra, Amplyx, Astellas, Basilea, Biosys, Cidara, Da Volterra, Entasis, F2G, Gilead, Matinas, MedPace, Menarini, Merck/MSD, Mylan, Nabriva, Noxxon, Octapharma, Paratek, Pfizer, PSI, Roche Diagnostics, Scynexis, and Shionogi, and received lecture honoraria from Al-Jazeera Pharmaceuticals, Astellas, Basilea, Gilead, Grupo Biotoscana, Merck/MSD and Pfizer. L.M.B. has received lecture honoraria from Astellas and Merck/MSD, and travel grants from 3M and Gilead. OB received speaker fees and/or travel grants from Pfizer, MSD, Roche and Sanofi and has been a consultant to bioMérieux and Mylan. F.M. is a consultant for Da Volterra, IPSEN, Servier and received research grants from Da Volterra, Sanofi and Servier. MJGTV has received research grants from 3M, Astellas Pharma, Da Volterra, Gilead Sciences, Gly-com, MaaT Pharma, Merck/MSD, Organobalance, Seres Therapeutics; speaker fees from Astellas Pharma, Basilea, Gilead Sciences, Merck/MSD, Organobalance, Pfizer and has been a consultant to Alb Fils Kliniken GmbH, Astellas Pharma, Bio-Mérieux, Da Vol-terra, Ferring, MaaT Pharma, Merck/MSD. The remaining authors declare no competing interests. Publisher Copyright: © 2021, The Author(s).
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