# Clostridium innocuum as an emerging multidrug-resistant antibiotic-associated diarrheal pathogen

> **NIH NIH R21** · LURIE CHILDREN'S HOSPITAL OF CHICAGO · 2020 · $194,160

## Abstract

PROJECT SUMMARY ABSTRACT
Antibiotic-associated diarrhea (AAD) is a very common problem; approximately 50% of hospitalized patients
receive antibiotics, and up to 25% of those patients develop AAD. While many AAD infectious etiologies, such
as Clostridium difficile infection (CDI), have been well described, a recent study from Taiwan characterized
Clostridium innocuum (CI) as a previously unrecognized cause of AAD with multidrug-resistance, including to
vancomycin. This study suggested that CI causes gastrointestinal illness indistinguishable from CDI, which can
include severe and pseudomembranous colitis, in both humans and an intestinal model of infection in mice.
This recognition of the pathogenic potential of CI is in contrast to its prior classification as a clinically innocuous
intestinal commensal. This was based on a single 1962 study that failed to demonstrate CI pathogenicity in a
non-intestinal mouse model. Our preliminary clinical, microbiologic, and genomic data support potential
reclassification of CI as an emerging pathogen. We have recently isolated CI from more than 20 children
diagnosed with CDI (in whom the contribution of CI to illness is unclear) and one adult with recurrent AAD (in
whom CI caused AAD). Further analysis suggests that many of these children were colonized with C. difficile
and had another unidentified diarrheal etiology. In addition, several of our CI strains were noted to be positive
for C. difficile toxins A/B by enzyme immunoassay (EIA). Thus, our preliminary data suggest a model whereby
some CI strains have the ability to produce a protein that is recognized by C. difficile anti-toxin antibodies, and
that CI may cause some cases of AAD, potentially related to this uncharacterized protein. To better
characterize the epidemiologic significance and microbiologic characteristics of this emerging pathogen in US
adults and children, we propose to: (1) Determine the clinical and molecular epidemiology of CI in symptomatic
and asymptomatic adults and children; (2a) Identify the CI protein responsible for C. difficile toxin A/B EIA
cross-reactivity, and (2b) Determine the association between this protein and CI pathogenicity. Because
vancomycin use for CDI is increasing in the US, selective pressure may favor a rise in clinical infections with
multidrug-resistant CI. Because of widespread use of C. difficile-specific diagnostic tests for CDI, diagnosis of
clinically indistinguishable CI AAD will require substantial clinical microbiology practice change. For these
reasons, it is imperative to understand the scope of CI AAD in the US. Successful completion of the proposed
studies will guide future investigation of the pathogenesis, diagnosis, and clinical characteristics of CI infection.
Our team and the Northwestern University academic environment possess the skills and resources necessary
for successful completion of the proposed studies, including assembly of patient cohorts, microbiology,
bacterial pathogenesis, p...

## Key facts

- **NIH application ID:** 9853735
- **Project number:** 5R21AI144549-02
- **Recipient organization:** LURIE CHILDREN'S HOSPITAL OF CHICAGO
- **Principal Investigator:** LARRY K KOCIOLEK
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $194,160
- **Award type:** 5
- **Project period:** 2019-01-24 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853735

## Citation

> US National Institutes of Health, RePORTER application 9853735, Clostridium innocuum as an emerging multidrug-resistant antibiotic-associated diarrheal pathogen (5R21AI144549-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9853735. Licensed CC0.

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