title: Identification of toxemia in patients with Clostridium difficile infection.
abstract: 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.
authors.affiliation: Department of Microbial Pathogenesis, University of Maryland Dental School, Baltimore, Maryland, United States of America.
authors.forename: Hua
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Microbial Pathogenesis, University of Maryland Dental School, Baltimore, Maryland, United States of America.
authors.forename: Kevin
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Microbial Pathogenesis, University of Maryland Dental School, Baltimore, Maryland, United States of America.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Microbial Pathogenesis, University of Maryland Dental School, Baltimore, Maryland, United States of America.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Microbial Pathogenesis, University of Maryland Dental School, Baltimore, Maryland, United States of America.
authors.forename: Lianfa
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Lydia L
authors.initials: LL
authors.lastname: Barlow
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America; Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: David M
authors.initials: DM
authors.lastname: Aronoff
authors.affiliation: University of Houston College of Pharmacy, Houston, Texas, United States of America; Baylor St. Luke's Medical Center, Houston, Texas, United States of America; University of Texas School of Public Health, Houston, Texas, United States of America.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Garey
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, United States of America; Texas Children's Microbiome Center, Texas Children's Hospital, Houston, Texas, United States of America.
authors.forename: Tor C
authors.initials: TC
authors.lastname: Savidge
authors.affiliation: Division of Gastroenterology & Hepatology, Department of Medicine, University of Maryland, Baltimore, Maryland, United States of America; VA Maryland Health Care System, Baltimore, Maryland, United States of America.
authors.forename: Erik C
authors.initials: EC
authors.lastname: von Rosenvinge
authors.affiliation: Department of Medicine, Harvard Medical School and Celiac Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Ciaran P
authors.initials: CP
authors.lastname: Kelly
authors.affiliation: Department of Microbial Pathogenesis, University of Maryland Dental School, Baltimore, Maryland, United States of America.
authors.forename: Hanping
authors.initials: H
authors.lastname: Feng
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D001426:Bacterial Proteins / Q000097:blood* / Q000737:chemistry / Q000276:immunology; D001427:Bacterial Toxins / Q000097:blood* / Q000737:chemistry / Q000276:immunology; D001681:Biological Assay; D001793:Blood Preservation; D002522:Chlorocebus aethiops; D016360:Clostridioides difficile / Q000276:immunology / Q000472:pathogenicity*; D004239:Diverticulitis, Colonic / Q000150:complications; D004761:Enterocolitis, Pseudomembranous / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D004768:Enterotoxins / Q000097:blood* / Q000737:chemistry / Q000276:immunology; D005188:False Negative Reactions; D005260:Female; D006031:Glycosylation; D006801:Humans; D016867:Immunocompromised Host; D007074:Immunoglobulin G / Q000097:blood; D009104:Multiple Trauma / Q000150:complications; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D012307:Risk Factors; D014115:Toxemia / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000276:immunology; D014709:Vero Cells; D055815:Young Adult; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; D007074:Immunoglobulin G; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile; D020830:rac1 GTP-Binding Protein