Fatal pseudomembranous colitis associated with a variant Clostridium difficile strain not detected by toxin a immunoassay

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 tox in variant strain of C difficile that was not detected by toxin A immunoass ay; 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 coli tis. Four stool specimens submitted over a 2-month period had tested negati ve on toxin A immunoassay, but a strain of C difficile with a 1.8-kb deleti on of the toxin A gene was recovered from each specimen. This strain, ident ified 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%) r egional clinical laboratories. Conclusions: Toxin A variant strains of C difficile cause serious disease a nd are undetectable in clinical laboratories that use only toxin A immunoas says for C. difficile testing.