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Fatal Pseudomembranous Colitis Associated with a Variant Clostridium difficile Strain Not Detected by Toxin A Immunoassay
- Stuart Johnson, MD;
- Sara A. Kent, MD;
- Kevin J. O'Leary, MD;
- Michelle M. Merrigan, MS;
- Susan P. Sambol, BS;
- Lance R. Peterson, MD; and
- Dale N. Gerding, MD
- From Veterans Affairs Chicago Health Care System, Lakeside Division, and Northwestern University Medical School, Chicago, Illinois.
Abstract
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.
Article and Author Information
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Grant Support: By the Department of Veterans Affairs Research Service and a Northwestern University Medical School Intramural Research Grant from the Northwestern Memorial Hospital Intramural Research Grants Programs.
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Requests for Single Reprints: Stuart Johnson, MD, Medical Service, Veterans Affairs Chicago Health Care System—Lakeside, 333 East Huron Street, Chicago, IL 60611; e-mail, stu-johnson{at}northwestern.edu.
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Current Author Addresses: Drs. Johnson and Gerding: Medical Service, Veterans Affairs Chicago Health Care System—Lakeside, 333 East Huron Street, Chicago, IL 60611.
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Drs. Kent and Peterson: Northwestern Memorial Hospital, 251 East Huron Street, Chicago, IL 60611-3058.
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Dr. O'Leary: Northwestern University, 675 North St. Clair, Chicago, IL 60611.
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Ms. Merrigan and Ms. Sambol: Northwestern University Medical School, 400 East Ontario Street, Chicago, IL 60611.
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Author Contributions: Conception and design: S. Johnson, D.N. Gerding.
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Analysis and interpretation of the data: S. Johnson, S.A. Kent, K.J. O'Leary, M.M. Merrigan, S.P. Sambol, D.N. Gerding.
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Drafting of the article: S. Johnson, S.A. Kent.
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Critical revision of the article for important intellectual content: L.R. Peterson, D.N. Gerding.
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Final approval of the article: S. Johnson, K.J. O'Leary, M.M. Merrigan, S.P. Sambol, L.R. Peterson, D.N. Gerding.
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Provision of study materials or patients: S.A. Kent, K.J. O'Leary.
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Obtaining of funding: S. Johnson, D.N. Gerding.
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Administrative, technical, or logistic support: L.R. Peterson.
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Collection and assembly of data: M.M. Merrigan, S.P. Sambol.
- Copyright ©2004 by the American College of Physicians
