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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
[+] Article, Author, and Disclosure Information

From Veterans Affairs Chicago Health Care System, Lakeside Division, and Northwestern University Medical School, Chicago, Illinois.

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.

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@northwestern.edu.

Current Author Addresses: Drs. Johnson and Gerding: Medical Service, Veterans Affairs Chicago Health Care System—Lakeside, 333 East Huron Street, Chicago, IL 60611.

Drs. Kent and Peterson: Northwestern Memorial Hospital, 251 East Huron Street, Chicago, IL 60611-3058.

Dr. O'Leary: Northwestern University, 675 North St. Clair, Chicago, IL 60611.

Ms. Merrigan and Ms. Sambol: Northwestern University Medical School, 400 East Ontario Street, Chicago, IL 60611.

Author Contributions: Conception and design: S. Johnson, D.N. Gerding.

Analysis and interpretation of the data: S. Johnson, S.A. Kent, K.J. O'Leary, M.M. Merrigan, S.P. Sambol, D.N. Gerding.

Drafting of the article: S. Johnson, S.A. Kent.

Critical revision of the article for important intellectual content: L.R. Peterson, D.N. Gerding.

Final approval of the article: S. Johnson, K.J. O'Leary, M.M. Merrigan, S.P. Sambol, L.R. Peterson, D.N. Gerding.

Provision of study materials or patients: S.A. Kent, K.J. O'Leary.

Obtaining of funding: S. Johnson, D.N. Gerding.

Administrative, technical, or logistic support: L.R. Peterson.

Collection and assembly of data: M.M. Merrigan, S.P. Sambol.

Ann Intern Med. 2001;135(6):434-438. doi:10.7326/0003-4819-135-6-200109180-00012
Text Size: A A A

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.


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Gross findings at autopsy performed 2 months after symptom onset.Left.Right.

Diffuse pseudomembranous colitis is demonstrated with characteristic yellow patches becoming confluent in some areas. The pseudomembranes did not involve the small intestine. Microscopic examination of pseudomembranous plaques at autopsy (hematoxylin–eosin stain; magnification, ×100). Sharply defined eruptions of exudate (composed of neutrophils, mucus, fibrin, and cellular debris) adhere to the damaged mucosal surface.

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Summary for Patients

Fatal Inflammatory Condition in a Patient with a Variant Bacterial Strain

The summary below is from the full report titled “Fatal Pseudomembranous Colitis Associated with a Variant Clostridium difficile Strain Not Detected by Toxin A Immunoassay.” It is in the 18 September 2001 issue of Annals of Internal Medicine (volume 135, pages 434-438). The authors are S Johnson, SA Kent, KJ O'Leary, MM Merrigan, SP Sambol, LR Peterson, and DN Gerding.


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