Identification of toxemia in patients with Clostridium difficile infection.

Yu H, Chen K, Wu J, Yang Z, Shi L, Barlow LL, Aronoff DM, Garey KW, Savidge TC, von Rosenvinge EC, Kelly CP, Feng H
PLoS One. 2015 10 (4): e0124235

PMID: 25885671 · PMCID: PMC4401762 · DOI:10.1371/journal.pone.0124235

Toxemia can develop in Clostridium difficile-infected animals, and correlates with severe and fulminant disease outcomes. Circumstantial evidence suggests that toxemia may occur in patients with C. difficile infection (CDI), but positive diagnosis is extremely rare. We analyzed the potential for C. difficile toxemia in patients, determined its characteristics, and assessed challenges. C. difficile toxins in serum from patients were tested using an ultrasensitive cell-based assay and further confirmed by Rac1 glucosylation assay. The factors that hinder a diagnosis of toxemia were assessed, including investigation of toxin stability, the level of toxins-specific neutralizing antibodies in sera and its effect on diagnosis limits. CDI patients develop detectable toxemia in some cases (2.3%). Toxins were relatively stable in stored sera. Neutralizing anti-toxin antibodies were present during infection and positively correlated with the diagnosis limits. Thus, the masking effect of toxin-specific neutralizing antibodies is the major obstacle in diagnosing C. difficile toxemia using cell-based bioassays.

MeSH Terms (27)

Animals Anti-Bacterial Agents Antibodies, Bacterial Antibodies, Neutralizing Bacterial Proteins Bacterial Toxins Biological Assay Blood Preservation Cercopithecus aethiops Clostridium difficile Diverticulitis, Colonic Enterocolitis, Pseudomembranous Enterotoxins False Negative Reactions Female Glycosylation Humans Immunocompromised Host Immunoglobulin G Multiple Trauma Protein Processing, Post-Translational Protein Stability rac1 GTP-Binding Protein Risk Factors Toxemia Vero Cells Young Adult

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