- C. difficile is the most common identifiable cause of antibiotic associated diarrhea.*
- C. difficile is an opportunistic organism which typically produces
two potent toxins, toxin A and toxin B. Some strains produce only toxin B, and some strains also produce a third, unrelated toxin (binary toxin). The role of binary toxin is uncertain and is not identified by most clinical diagnostic tests.
- The discovery of C. difficile strains (initially in North America
and subsequently Europe) that have increased virulence has emphasized the need for effective diagnostic and control
- The clinical manifestations of infection with toxin-producing
strains of C. difficile range from symptomless carriage, to mild or moderate diarrhea, to fulminant and sometimes fatal pseudomembranous colitis.
- A case definition of Clostridium difficile infection (CDI) should
include the presence of symptoms (usually diarrhea) and either a positive stool test for C. difficile toxins or toxigenic C. difficile, or direct visualization revealing pseudomembranous colitis.
- A history of treatment with antimicrobial or antineoplastic agents within the previous 8 weeks is present in the majority of patients.
- Rarely (< 1%), a symptomatic patient will present with ileus and colonic distension with minimal or no diarrhea.
- Minimize frequency, duration and number of antimicrobial agents prescribed to reduce CDI risk (A-II).
- Implement an antimicrobial stewardship program (A-II).
- Antimicrobials to be targeted should be based on local epidemiology and the strains present, but cephalosporin and clindamycin restriction (excluding surgical antibiotic prophylaxis) may be particularly useful (C-III).
- No recommendations can be made regarding prevention of
recurrent CDI in patients requiring continued antimicrobial
therapy for an underlying infection (C-III).
Diagnosis and Assessment
- Stool culture is the most sensitive test and is essential for epidemiological studies (A-II).
- Testing for C. difficile or its toxins should be performed only on diarrheal (unformed) stool unless ileus due to C. difficile is suspected (B-II).
- Testing of stools of asymptomatic patients, including use as a
test of cure, is not recommended except for epidemiological
- Enzyme immunoassay (EIA) testing for toxin A and B is rapid but is less sensitive than the cell cytotoxin assay and is thus a sub-optimal alternative approach for diagnosis (B-II).
- Comment: One potential strategy to overcome this problem is a two-step method using EIA for glutamate dehydrogenase (GDH) as an initial screen and the cell cytotoxicity assay or toxigenic culture as the confirmatory test only on GDH
positive stools. This approach remains an interim recommendation (B-II).
- Polymerase chain reaction (PCR) testing appears to be rapid, sensitive and specific and may ultimately address testing concerns. More data on utility are necessary before this methodology can be recommended for routine testing (B-II).
- Repeat testing during the same episode of diarrhea is of limited value and should be discouraged (B-II).