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.