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

Dieterle, Michael G.; Putler, Rosemary; Perry, D. Alexander; Menon, Anitha; Abernathy-Close, Lisa; Perlman, Naomi; Penkevich, Aline; Standke, Alex; Keidan, Micah; Vendrov, Kimberly C.; Bergin, Ingrid L.; Young, Vincent B.; Rao, Krishna

doi:10.1128/mbio.00180-20

Cited by 20 publications

(19 citation statements)

References 29 publications

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“…However, we found that there was no difference in cecum and colon scores between clindamycin- and PEG-treated mice that were challenged with C. difficile at 4 days postchallenge ( Fig. 3D ), the time point typically examined in C. difficile 630-challenged mice ( 28 ). We also looked at 6 days postchallenge because that was when there was a large difference in C. difficile density between PEG- and clindamycin-treated mice ( Fig.…”

Section: Resultsmentioning

confidence: 84%

An Osmotic Laxative Renders Mice Susceptible to Prolonged Clostridioides difficile Colonization and Hinders Clearance

Tomkovich

Taylor

King

et al. 2021

mSphere

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Section: Resultsmentioning

confidence: 84%

An Osmotic Laxative Renders Mice Susceptible to Prolonged Clostridioides difficile Colonization and Hinders Clearance

Tomkovich

Taylor

King

et al. 2021

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“…However, we found there was no difference in cecum and colon scores between clindamycin and PEG-treated mice that were challenged with C. difficile at 4 days post-challenge (Fig. 3D), the time point typically examined in C. difficile challenged mice (28). We also looked at 6 days post-challenge because that was when there was a large difference in C. difficile density between PEG-and clindamycin-treated mice (Fig.…”

Section: -Day Laxative Treatment Differentially Disrupted the Fecal Microbiota Compared To Clindamycin Treatment Since Osmotic Laxatives mentioning

confidence: 89%

An osmotic laxative renders mice susceptible to prolonged Clostridioides difficile colonization and hinders clearance

Tomkovich

Taylor

King

et al. 2021

Preprint

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Antibiotics are a major risk factor for Clostridioides difficile infections (CDIs) because of their impact on the microbiota. However, non-antibiotic medications such as the ubiquitous osmotic laxative polyethylene glycol (PEG) 3350 also alter the microbiota. Clinicians also hypothesize that PEG helps clear C. difficile. But whether PEG impacts CDI susceptibility and clearance is unclear. To examine how PEG impacts susceptibility, we treated C57Bl/6 mice with 5-day and 1-day doses of 15% PEG in the drinking water and then challenged the mice with C. difficile 630. We used clindamycin-treated mice as a control because they consistently clear C. difficile within 10 days post-challenge. PEG treatment alone was sufficient to render mice susceptible and 5-day PEG-treated mice remained colonized for up to 30 days post-challenge. In contrast, 1-day PEG treated mice were transiently colonized, clearing C. difficile within 7 days post-challenge. To examine how PEG treatment impacts clearance, we administered a 1-day PEG treatment to clindamycin-treated, C. difficile-challenged mice. Administering PEG to mice after C. difficile challenge prolonged colonization up to 30 days post-challenge. When we trained a random forest model with community data from 5 days post-challenge, we were able to predict which mice would exhibit prolonged colonization (AUROC = 0.90). Examining the dynamics of these bacterial populations during the post-challenge period revealed patterns in the relative abundances of Bacteroides, Enterobacteriaceae, Porphyromonadaceae, Lachnospiraceae, and Akkermansia that were associated with prolonged C. difficile colonization in PEG-treated mice. Thus, the osmotic laxative, PEG, rendered mice susceptible to C. difficile colonization and hindered clearance.

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“…The AuROCs of these models in predicting attributable complications were 0.874 and 0.84, respectively. 84 …”

Section: Microbiologic Factors Associated With CDI Outcomesmentioning

confidence: 99%

Defining the black box: a narrative review of factors associated with adverse outcomes from severe Clostridioides difficile infection

Ressler

Wang

Rao

2021

Therap Adv Gastroenterol

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In the United States, Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated infection, affecting nearly half a million people and resulting in more than 20,000 in-hospital deaths every year. It is therefore imperative to better characterize the intricate interplay between C. difficile microbial factors, host immunologic signatures, and clinical features that are associated with adverse outcomes of severe CDI. In this narrative review, we discuss the implications of C. difficile genetics and virulence factors in the molecular epidemiology of CDI, and the utility of early biomarkers in predicting the clinical trajectory of patients at risk of developing severe CDI. Furthermore, we identify associations between host immune factors and CDI outcomes in both animal models and human studies. Next, we highlight clinical factors including renal dysfunction, aging, blood biomarkers, level of care, and chronic illnesses that can affect severe CDI diagnosis and outcome. Finally, we present our perspectives on two specific treatments pertinent to patient outcomes: metronidazole administration and surgery. Together, this review explores the various venues of CDI research and highlights the importance of integrating microbial, host, and clinical data to help clinicians make optimal treatment decisions based on accurate prediction of disease progression.

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

Cited by 20 publications

References 29 publications

An Osmotic Laxative Renders Mice Susceptible to Prolonged Clostridioides difficile Colonization and Hinders Clearance

An Osmotic Laxative Renders Mice Susceptible to Prolonged Clostridioides difficile Colonization and Hinders Clearance

An osmotic laxative renders mice susceptible to prolonged Clostridioides difficile colonization and hinders clearance

Defining the black box: a narrative review of factors associated with adverse outcomes from severe Clostridioides difficile infection

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