Test Catalog

Interpretive Handbook

Test 35149 :
Clostridium difficile Toxin, Molecular Detection, PCR, Feces

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Clostridium difficile is the cause of C difficile-associated diarrhea (CDAD), an antibiotic-associated diarrhea, and pseudomembranous colitis (PMC). In these disorders bacterial overgrowth of C difficile develops in the colon, typically as a consequence of antibiotic usage. Clindamycin and broad-spectrum cephalosporins have been most frequently associated with CDAD and PMC, but almost all antimicrobials may be responsible. Disease is related to production of toxin A and B. Treatment typically involves withdrawal of the associated antimicrobials and, if symptoms persist, orally administered and intraluminally active metronidazole, vancomycin, or fidaxomicin. Intravenous metronidazole may be used if an oral agent cannot be administered. In recent years, a more severe form of CDAD with increased morbidity and mortality has been recognized as being caused by an epidemic toxin-hyperproducing strain of C difficile (NAP1 strain). Many toxin-hyperproducing isolates also contain the binary toxin gene and are resistant quinolones. This test does not differentiate between toxin-hyperproducing and nontoxin-hyperproducing strains.


Traditionally, diagnosis relied upon 1) clinical and epidemiologic features, 2) culture (which is labor intensive and time consuming), 3) cytotoxicity assays, which are labor intensive and time consuming, and 4) toxin detection immunoassays (which are insensitive). The described PCR assay detects the regulatory gene (tcdC) responsible for production of toxins A and B. This test is used for rapid diagnosis of CDAD and PMC enabling prompt treatment that may reduce hospital stays for inpatients with CDAD.

Useful For Suggests clinical disorders or settings where the test may be helpful

Sensitive, specific, and rapid diagnosis of Clostridium difficile-associated diarrhea and pseudomembranous colitis

Interpretation Provides information to assist in interpretation of the test results

A positive PCR result for the presence of the gene regulating toxin production (tcdC) indicates the presence of Clostridium difficile and toxin A and/or B.


A negative result indicates the absence of detectable C difficile tcdC DNA in the specimen, but does not rule-out C difficile infection. False-negative results may occur due to inhibition of PCR, sequence variability underlying the primers or probes, or the presence of C difficile in quantities less than the limit of detection of the assay.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

The assay must be performed on fresh stools, fresh-frozen stools, or stools in transport medium.


The assay has not been validated as a test of cure. Since nucleic acid may persist after effective treatment, follow-up testing of a positive result is not recommended.


Interfering substances in the stool may affect the accuracy of the assay; results should always be interpreted in conjunction with clinical and epidemiologic findings.


Submission of more than 1 specimen for testing is not recommended.


Testing of colostomy, ileostomy, or colonoscopically collected specimens has not been validated.


Patients may asymptomatically carry Clostridium difficile; clinical correlation is needed when deciding how to manage patients with a positive test result.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Not applicable

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Aichinger E, Schleck CD, Harmsen WS, et al: Nonutility of repeat laboratory testing for detection of Clostridium difficile by use of PCR or enzyme immunoassay. J Clin Microbiol 2008;46:3795-3797

2. Sloan LM, Duresko BJ, Gustafson DR, et al: Comparison of real-time PCR for detection of the tcdC gene with four toxin immunoassays and culture in diagnosis of Clostridium difficile infection. J Clin Microbiol 2008;46:1996-2001

3. Verdoorn BP, Orenstein R, Rosenblatt JE, et al: High prevalence of tcdC deletion-carrying Clostridium difficile and lack of association with disease severity. Diagn Microbiol Infect Dis 2010;66:24-28

4. Karre T, Sloan L, Patel R, et al: Comparison of two commercial molecular assays to a laboratory-developed molecular assay for diagnosis of Clostridium difficile infection. J Clin Microbiol 2011;49:725-727

Tell Us What You Think