The systemic inflammatory response to Clostridium difficile infection.

The systemic inflammatory response to Clostridium difficile infection (CDI) is incompletely defined, particularly for patients with severe disease.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.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.A broad systemic inflammatory response occurs during CDI and severe cases appear to differ from non-severe infections

Global systemic inflammatory responses in <i>C. difficile</i> infection (CDI) cases and inpatient controls.

<p>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 (<i>P</i> = .051).</p

Thirty inflammatory mediators (cytokines, chemokines, and growth factors) measured in the circulation of study subjects.

<p>Thirty inflammatory mediators (cytokines, chemokines, and growth factors) measured in the circulation of study subjects.</p

Simple logistic regression results for serum inflammatory mediators (cytokines, chemokines, and growth factors) in patients with <i>Clostridium difficile</i> infection (CDI) vs. matched inpatient controls who tested negative for CDI and asymptomatic outpatient controls (all units in log^­₁₀ pg/mL).

1<p>Versus patients with CDI.</p

Global systemic inflammatory responses in <i>C. difficile</i> infection (CDI) cases and outpatient controls.

<p>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 (<i>P</i><.001).</p

Patient characteristics.

<p><i>Abbreviations</i>: CDI, <i>Clostridium difficile</i> infection; IQR, interquartile range; NA, not applicable; PPI, proton pump inhibitor; SD, standard deviation; WBC, white blood cell count. Missing data is indicated by a hyphen.</p>1<p>Diarrhea, but no CDI.</p>2<p>Healthy patients without diarrhea or CDI.</p>3<p><i>P</i> values compare control groups to cases and use the unpaired t-test for means/Mann-Whitney test for medians (continuous variables) or the two sample z-test for proportions (categorical variables).</p>4<p>Temperature > 38°C.</p>5<p>thousands of cells per mm³_.</p>6<p>Intensive care unit admission, colectomy, or death attributed to CDI within 30 days of diagnosis.</p>7<p>All-cause 30-day mortality.</p

Testing algorithm for <i>Clostridium difficile</i> infection.

<p>This flow diagram illustrates this University of Michigan diagnostic testing algorithm for detecting toxigenic <i>Clostridium difficile</i> in stool. <i>Abbreviations</i>: CDI, <i>Clostridium difficile</i> infection; EIA, enzyme immunoassay; GDH, glutamate dehydrogenase; PCR, polymerase chain reaction.</p