The systemic inflammatory response to Clostridium difficile infection

Krishna Rao, John R Erb-Downward, Seth T Walk, Dejan Micic, Nicole Falkowski, Kavitha Santhosh, Jill A Mogle, Cathrin Ring, Vincent B Young, Gary B Huffnagle, David M Aronoff, Krishna Rao, John R Erb-Downward, Seth T Walk, Dejan Micic, Nicole Falkowski, Kavitha Santhosh, Jill A Mogle, Cathrin Ring, Vincent B Young, Gary B Huffnagle, David M Aronoff

Abstract

Background: The systemic inflammatory response to Clostridium difficile infection (CDI) is incompletely defined, particularly for patients with severe disease.

Methods: Analysis of 315 blood samples from 78 inpatients with CDI (cases), 100 inpatients with diarrhea without CDI (inpatient controls), and 137 asymptomatic outpatient controls without CDI was performed. Serum or plasma was obtained from subjects at the time of CDI testing or shortly thereafter. Severe cases had intensive care unit admission, colectomy, or death due to CDI within 30 days after diagnosis. Thirty different circulating inflammatory mediators were quantified using an antibody-linked bead array. Principal component analysis (PCA), multivariate analysis of variance (MANOVA), and logistic regression were used for analysis.

Results: Based on MANOVA, cases had a significantly different inflammatory profile from outpatient controls but not from inpatient controls. In logistic regression, only chemokine (C-C motif) ligand 5 (CCL5) levels were associated with cases vs. inpatient controls. Several mediators were associated with cases vs. outpatient controls, especially hepatocyte growth factor, CCL5, and epithelial growth factor (inversely associated). Eight cases were severe and associated with elevations in IL-8, IL-6, and eotaxin.

Conclusions: A broad systemic inflammatory response occurs during CDI and severe cases appear to differ from non-severe infections.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Testing algorithm for Clostridium difficile…
Figure 1. Testing algorithm for Clostridium difficile infection.
This flow diagram illustrates this University of Michigan diagnostic testing algorithm for detecting toxigenic Clostridium difficile in stool. Abbreviations: CDI, Clostridium difficile infection; EIA, enzyme immunoassay; GDH, glutamate dehydrogenase; PCR, polymerase chain reaction.
Figure 2. Detectability of circulating inflammatory mediators…
Figure 2. Detectability of circulating inflammatory mediators in Clostridium difficile infection (CDI).
Results for cases (panel A), inpatient controls (panel B), and outpatient controls (panel C) are shown.
Figure 3. Global systemic inflammatory responses in…
Figure 3. Global systemic inflammatory responses in C. difficile infection (CDI) cases and inpatient controls.
Principal component analysis (PCA) (panel A) results are shown for CDI cases and inpatient controls. The individual inflammatory mediators’ effects on the PCA were plotted as biplots (panel B). In biplots the arrows indicate the direction of maximum change while the length of arrows represents the magnitude of the change. The PCA centroids were not significantly different by permutational MANOVA testing (P = .051).
Figure 4. Global systemic inflammatory responses in…
Figure 4. Global systemic inflammatory responses in C. difficile infection (CDI) cases and outpatient controls.
Principal component analysis (PCA) (panel A) results are shown for CDI cases and outpatient controls. The individual inflammatory mediators’ effects on the PCA were plotted as biplots (panel B). In biplots the arrows indicate the direction of maximum change while the length of arrows represents the magnitude of the change. The PCA centroids were different by permutational MANOVA testing (P<.001).

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Source: PubMed

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