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, 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.

Here, the authors report the incidence of Clostridioides difficile infection (CDI) and assess potential clinical characteristics and biomarkers to predict CDI in 1,007 patients of 50 years and above receiving newly initiated antibiotic treatment.

Details

Title
Incidence and predictive biomarkers of Clostridioides difficile infection in hospitalized patients receiving broad-spectrum antibiotics
Author
van Werkhoven Cornelis H 1   VIAFID ORCID Logo  ; Ducher Annie 2 ; Berkell Matilda 3   VIAFID ORCID Logo  ; Mysara Mohamed 4   VIAFID ORCID Logo  ; Lammens, Christine 3 ; Torre-Cisneros, Julian 5   VIAFID ORCID Logo  ; Rodríguez-Baño Jesús 6   VIAFID ORCID Logo  ; Herghea Delia 7 ; Cornely, Oliver A 8   VIAFID ORCID Logo  ; Biehl, Lena M 9 ; Bernard, Louis 10 ; Angeles, Dominguez-Luzon M 11 ; Maraki Sofia 12   VIAFID ORCID Logo  ; Barraud Olivier 13   VIAFID ORCID Logo  ; Nica, Maria 14 ; Jazmati Nathalie 15 ; Sablier-Gallis Frederique 2 ; de Gunzburg Jean 2   VIAFID ORCID Logo  ; Mentré France 16 ; Malhotra-Kumar Surbhi 3   VIAFID ORCID Logo  ; Bonten Marc J M 17 ; Vehreschild Maria J G T 18   VIAFID ORCID Logo  ; Engbers, Annemarie M, S 19 ; de Regt Marieke J A 20 ; Goossens, Herman 3 ; Britto, Xavier Basil 3 ; Marie-Noelle, Bouverne 2 ; Monsieurs Pieter 21 ; Merle Uta 22 ; Stallmach Andreas 23 ; Rupp, Jan 24 ; Bogner, Johannes 25 ; Lübbert Christoph 26 ; Silling Gerda 27 ; Witzke, Oliver 28 ; Gikas Achilleas 12 ; Daikos, George 29 ; Tsiodras Sotirios 30 ; Skoutelis Athanasios 31 ; Sambatakou Helen 32 ; Pujol Miquel 11 ; Aguado, Jose M 33 ; Bouza Emilio 34 ; Cobo, Javier 35 ; Almirante Benito 36 ; Florescu, Simin A 37 ; Vata Andrei 38 ; Hristea Adriana 39 ; Lupse Mihaela 40 ; Postil Deborah 41 ; Molina, Jean-Michel 42 ; De Lastours Victoire 43 ; Guimard, Thomas 44 ; Jean-Philippe, Talarmin 45 ; Duval, Xavier 46 ; Launay Odile 47 

1  University Medical Center Utrecht, Utrecht University, Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands 
2  Da Volterra, Paris, France (GRID:grid.433274.5) 
3  Vaccine & Infectious Disease Institute, University of Antwerp, Laboratory of Medical Microbiology, Antwerp, Belgium (GRID:grid.5284.b) (ISNI:0000 0001 0790 3681) 
4  Vaccine & Infectious Disease Institute, University of Antwerp, Laboratory of Medical Microbiology, Antwerp, Belgium (GRID:grid.5284.b) (ISNI:0000 0001 0790 3681); Belgian Nuclear Research Centre, SCK.CEN, Microbiology Unit, Environment Health and Safety, Mol, Belgium (GRID:grid.8953.7) (ISNI:0000 0000 9332 3503) 
5  Reina Sofia University Hospital, University of Cordoba (UCO), Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Cordoba, Spain (GRID:grid.5284.b) 
6  Hospital Universitario Virgen Macarena, Unidad Clínica de Enfermedades Infecciosas y Microbiología, Sevilla, Spain (GRID:grid.411375.5) (ISNI:0000 0004 1768 164X); Universidad de Sevilla, Instituto de Biomedicina de Sevilla (IBiS), Departamento de Medicina, Sevilla, Spain (GRID:grid.414816.e) (ISNI:0000 0004 1773 7922) 
7  Oncology Institute Prof. Dr. I Chiricuta, Cluj Napoca, Romania (GRID:grid.414816.e) 
8  Faculty of Medicine and University Hospital of Cologne, University of Cologne, Department I of Internal Medicine, Cologne, Germany (GRID:grid.6190.e) (ISNI:0000 0000 8580 3777); University of Cologne, Faculty of Medicine and University Hospital Cologne, Chair Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany (GRID:grid.6190.e) (ISNI:0000 0000 8580 3777); Partner Site Bonn-Cologne, German Centre for Infection Research (DZIF), Cologne, Germany (GRID:grid.6190.e) 
9  Faculty of Medicine and University Hospital of Cologne, University of Cologne, Department I of Internal Medicine, Cologne, Germany (GRID:grid.6190.e) (ISNI:0000 0000 8580 3777); Partner Site Bonn-Cologne, German Centre for Infection Research (DZIF), Cologne, Germany (GRID:grid.6190.e) 
10  Centre hospitalo-universitaire de Tours, Tours, France (GRID:grid.6190.e) 
11  Universitat de Barcelona, Hospital Universitari de Bellvitge, Barcelona, Spain (GRID:grid.5841.8) (ISNI:0000 0004 1937 0247) 
12  University Hospital of Heraklion, Heraklion, Greece (GRID:grid.412481.a) 
13  Université Limoges, INSERM U1092, Centre Hospitalier Universitaire de Limoges, Limoges, France (GRID:grid.412481.a) 
14  Infectious and Tropical Diseases Hospital “Dr. Victor Babes”, Bucharest, Romania (GRID:grid.412481.a) 
15  Immunology and Hygiene, University of Cologne, Institute for Medical Microbiology, Cologne, Germany (GRID:grid.6190.e) (ISNI:0000 0000 8580 3777); Labor Dr. Wisplinghoff, Cologne, Germany (GRID:grid.6190.e) 
16  Université de Paris, INSERM, IAME, Paris, France (GRID:grid.433274.5) 
17  University Medical Center Utrecht, Utrecht University, Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands (GRID:grid.5284.b); University Medical Center Utrecht, Utrecht University, Department of Medical Microbiology, Utrecht, the Netherlands (GRID:grid.5284.b) 
18  Faculty of Medicine and University Hospital of Cologne, University of Cologne, Department I of Internal Medicine, Cologne, Germany (GRID:grid.6190.e) (ISNI:0000 0000 8580 3777); Partner Site Bonn-Cologne, German Centre for Infection Research (DZIF), Cologne, Germany (GRID:grid.6190.e); University Hospital Frankfurt, Goethe University Frankfurt, Department of Internal Medicine, Infectious Diseases, Frankfurt am Main, Germany (GRID:grid.6190.e) 
19  University Medical Center Utrecht, Utrecht University, Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands (GRID:grid.6190.e) 
20  University Medical Center Utrecht, Department of Internal Medicine and Infectious Diseases, Utrecht, the Netherlands (GRID:grid.7692.a) (ISNI:0000000090126352) 
21  Belgian Nuclear Research Centre, SCK.CEN, Microbiology Unit, Environment Health and Safety, Mol, Belgium (GRID:grid.8953.7) (ISNI:0000 0000 9332 3503) 
22  Universitätsklinikum Heidelberg, Heidelberg, Germany (GRID:grid.5253.1) (ISNI:0000 0001 0328 4908) 
23  Universitätsklinikum Jena, Jena, Germany (GRID:grid.275559.9) (ISNI:0000 0000 8517 6224) 
24  Universitätsklinikum Schleswig-Holstein, Lübeck, Germany (GRID:grid.412468.d) (ISNI:0000 0004 0646 2097) 
25  Klinikum der Universität München, München, Germany (GRID:grid.411095.8) (ISNI:0000 0004 0477 2585) 
26  Universitätsklinikum Leipzig, Leipzig, Germany (GRID:grid.411339.d) (ISNI:0000 0000 8517 9062) 
27  Universitätsklinikum Aachen, Aachen, Germany (GRID:grid.412301.5) (ISNI:0000 0000 8653 1507) 
28  Universitätsklinikum Essen, Essen, Germany (GRID:grid.410718.b) (ISNI:0000 0001 0262 7331) 
29  Laiko General Hospital, Athens, Greece (GRID:grid.411565.2) (ISNI:0000 0004 0621 2848) 
30  University General Hospital ATTIKON, Athens, Greece (GRID:grid.411449.d) (ISNI:0000 0004 0622 4662) 
31  Evangelismos General Hospital, Athens, Greece (GRID:grid.414655.7) (ISNI:0000 0004 4670 4329) 
32  Ippokratio Hospital, Athens, Greece (GRID:grid.414655.7) 
33  Hospital Universitario 12 de Octubre, Madrid, Spain (GRID:grid.144756.5) (ISNI:0000 0001 1945 5329) 
34  Hospital Universitario Gregorio Marañón, Madrid, Spain (GRID:grid.410526.4) (ISNI:0000 0001 0277 7938) 
35  Hospital Universitario Ramón y Cajal, Madrid, Spain (GRID:grid.411347.4) (ISNI:0000 0000 9248 5770) 
36  Hospital Universitari Vall d’Hebrón, Barcelona, Spain (GRID:grid.411083.f) (ISNI:0000 0001 0675 8654) 
37  Infectious and Tropical Diseases Hospital “Dr. Victor Babes”, Bucharest, Romania (GRID:grid.411083.f) 
38  Clinical Hospital of Infectious Diseases of Iasi, Iasi, Romania (GRID:grid.411083.f) 
39  The National Institute of Infectious Diseases Matei Bals, Bucharest, Romania (GRID:grid.8194.4) (ISNI:0000 0000 9828 7548) 
40  Cluj Napoca Infectious Disease Clinical Hospital, Cluj Napoca, Romania (GRID:grid.8194.4) 
41  Université Limoges, INSERM U1092, Centre Hospitalier Universitaire de Limoges, Limoges, France (GRID:grid.8194.4) 
42  Hôpital St Louis, Paris, France (GRID:grid.413328.f) (ISNI:0000 0001 2300 6614) 
43  APHP Beaujon, Paris, France (GRID:grid.413328.f) 
44  Centre Hospitalier Départemental Vendée, La Roche sur Yon, France (GRID:grid.477015.0) (ISNI:0000 0004 1772 6836) 
45  CH de Cornouaille, Quimper, France (GRID:grid.477015.0) 
46  APHP Bichat, Paris, France (GRID:grid.477015.0) 
47  APHP Hôpital Cochin, Paris, France (GRID:grid.411784.f) (ISNI:0000 0001 0274 3893) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-021-22269-y
ProQuest document ID
2512386634
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.