Fatal Pseudomembranous Colitis Associated with a Variant Clostridium difficile Strain Not Detected by Toxin A Immunoassay

作者：Stuart Johnson, Sara A. Kent, Kevin J. O’Leary, Michelle M. Merrigan, Susan P. Sambol, Lance R. Peterson, Dale N. Gerding · 发表于：Annals of Internal Medicine · 年份：2001 · DOI：10.7326/0003-4819-135-6-200109180-00012 · 被引用次数：147 · 研究领域：Clostridium difficile and Clostridium perfringens research、Antimicrobial Resistance in Staphylococcus、Bacillus and Francisella bacterial research

BACKGROUND: Many clinical laboratories use toxin A immunoassays to test for Clostridium difficile. OBJECTIVE: To describe the clinical course of a patient infected with a toxin variant strain of C. difficile that was not detected by toxin A immunoassay; to genetically characterize this strain; and to estimate the number of laboratories that use only toxin A immunoassays. DESIGN: Case report, molecular investigation, and laboratory survey. SETTING: Tertiary care hospital in Chicago, Illinois. PATIENT: An 86-year-old man. MEASUREMENTS: Restriction endonuclease analysis, polymerase chain reaction, and survey of regional clinical laboratories. RESULTS: An elderly hospitalized man died of advanced pseudomembranous colitis. Four stool specimens submitted over a 2-month period had tested negative on toxin A immunoassay, but a strain of C. difficile with a 1.8-kb deletion of the toxin A gene was recovered from each specimen. This strain, identified as restriction endonuclease analysis type CF4, is closely related to a widely disseminated variant, toxinotype VIII. Toxin A immunoassay was the only test being performed for detection of C. difficile at 31 of 67 (46%) regional clinical laboratories. CONCLUSIONS: Toxin A variant strains of C. difficile cause serious disease and are undetectable in clinical laboratories that use only toxin A immunoassays for C. difficile testing.