Microbiota-associated Risk Factors for Clostridioides difficile Acquisition in Hospitalized Patients: A Prospective, Multicentric Study.


Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213

Informations de publication

Date de publication:
02 11 2021
Historique:
received: 17 01 2020
pubmed: 27 6 2020
medline: 11 11 2021
entrez: 27 6 2020
Statut: ppublish

Résumé

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. 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. 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. Gemmiger spp., Odoribacter splanchnicus, Ruminococcus bromii and other Ruminococci were associated with a decreased risk of C. difficile acquisition. DRKS00005335.

Sections du résumé

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.

Identifiants

pubmed: 32589701
pii: 5863409
doi: 10.1093/cid/ciaa871
doi:

Substances chimiques

Bacterial Toxins 0

Types de publication

Journal Article Multicenter Study Observational Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2625-e2634

Subventions

Organisme : German Center for Infection Research
Organisme : State of Lower Saxony
ID : 2889

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Auteurs

Philipp Solbach (P)

Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
German Center for Infection Research, Partner Site Hannover-Braunschweig, Germany.
Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
Medical Department I, University Hospital Schleswig-Holstein, Lübeck, Germany.

Patrick Chhatwal (P)

German Center for Infection Research, Partner Site Hannover-Braunschweig, Germany.
Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.

Sabrina Woltemate (S)

German Center for Infection Research, Partner Site Hannover-Braunschweig, Germany.
Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.

Evelina Tacconelli (E)

Division of Infectious Diseases, Department of Internal Medicine 1, Tübingen University Hospital, Tübingen, Germany.
Division of Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, Italy.
German Center for Infection Research, Partner Site Tübingen, Germany.

Michael Buhl (M)

German Center for Infection Research, Partner Site Tübingen, Germany.
Institute of Medical Microbiology and Hygiene, Tübingen University Hospital, Tübingen, Germany.

Ingo B Autenrieth (IB)

German Center for Infection Research, Partner Site Tübingen, Germany.
Institute of Medical Microbiology and Hygiene, Tübingen University Hospital, Tübingen, Germany.

Maria J G T Vehreschild (MJGT)

1st Department of Internal Medicine, University Hospital Cologne, Cologne, Germany.
German Center for Infection Research, Partner Site Bonn-Cologne, Germany.
Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany.

Nathalie Jazmati (N)

German Center for Infection Research, Partner Site Bonn-Cologne, Germany.
Institute for Medical Microbiology, Immunology and Hygiene, University Hospital Cologne, Cologne, Germany, currently: Laboratory Dr. Wisplinghoff, Cologne, Germany.

Markus Gerhard (M)

Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany.
German Center for Infection Research, Partner Site Munich, Germany.

Christoph K Stein-Thoeringer (CK)

German Center for Infection Research, Partner Site Munich, Germany.
Microbiome and Cancer Research Division, German Center for Cancer Research, Heidelberg, Germany.

Jan Rupp (J)

Department of Infectious Diseases and Microbiology, University Hospital Schleswig-Holstein, Lübeck, Germany.
German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Germany.

Kurt Ulm (K)

Institute of Medical Informatics, Statistics and Epidemiology, Technische Universität München, Munich, Germany.

Armin Ott (A)

Institute of Medical Informatics, Statistics and Epidemiology, Technische Universität München, Munich, Germany.

Florian Lasch (F)

Institute for Biometry, Hannover Medical School, Hannover, Germany.

Armin Koch (A)

Institute for Biometry, Hannover Medical School, Hannover, Germany.

Michael P Manns (MP)

Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
German Center for Infection Research, Partner Site Hannover-Braunschweig, Germany.

Sebastian Suerbaum (S)

German Center for Infection Research, Partner Site Hannover-Braunschweig, Germany.
Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
German Center for Infection Research, Partner Site Munich, Germany.
Chair of Medical Microbiology and Hospital Epidemiology, Max von Pettenkofer Institute, Faculty of Medicine, LMU Munich, Munich, Germany.

Oliver Bachmann (O)

Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
German Center for Infection Research, Partner Site Hannover-Braunschweig, Germany.

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