Systemic Inflammatory Mediators Are Effective Biomarkers for Predicting Adverse Outcomes in Clostridioides difficile Infection

Author:

Dieterle Michael G.12ORCID,Putler Rosemary3,Perry D. Alexander3,Menon Anitha3,Abernathy-Close Lisa2ORCID,Perlman Naomi S.3,Penkevich Aline3,Standke Alex3,Keidan Micah3,Vendrov Kimberly C.3,Bergin Ingrid L.4,Young Vincent B.23ORCID,Rao Krishna3ORCID

Affiliation:

1. Medical Scientist Training Program, University of Michigan Medical School, Ann Arbor, Michigan, USA

2. Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA

3. Infectious Diseases Division, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA

4. Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan, USA

Abstract

Each year in the United States, Clostridioides difficile causes nearly 500,000 gastrointestinal infections that range from mild diarrhea to severe colitis and death. The ability to identify patients at increased risk for severe disease or mortality at the time of diagnosis of C. difficile infection (CDI) would allow clinicians to effectively allocate disease modifying therapies. In this study, we developed models consisting of only a small number of serum biomarkers that are capable of predicting both 30-day all-cause mortality and adverse outcomes of patients at time of CDI diagnosis. We were able to validate these models through experimental mouse infection. This provides evidence that the biomarkers reflect the underlying pathophysiology and that our mouse model of CDI reflects the pathogenesis of human infection. Predictive models can not only assist clinicians in identifying patients at risk for severe CDI but also be utilized for targeted enrollment in clinical trials aimed at reduction of adverse outcomes from severe CDI.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | NIH | National Institute of General Medical Sciences

HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases

U-M | Michigan Institute for Clinical and Health Research

WFU | Claude Pepper Older Americans Independence Center, Wake Forest School of Medicine

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

Reference33 articles.

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2. The Systemic Inflammatory Response to Clostridium difficile Infection

3. Novel therapies and preventative strategies for primary and recurrentClostridium difficileinfections

4. US Food and Drug Administration. 2019. Important safety alert regarding use of fecal microbiota for transplantation and risk of serious adverse reactions due to transmission of multi-drug resistant organisms. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/important-safety-alert-regarding-use-fecal-microbiota-transplantation-and-risk-serious-adverse.

5. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)

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