- 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).
Selecting a Treatment Regimen
- Discontinue inciting antimicrobials as soon as possible since this may influence the risk of CDI recurrence (A-II).
- If possible, avoid antiperistaltic agents since they may obscure symptoms and precipitate toxic megacolon (C-III).
- Metronidazole is the drug of choice for the initial episode of
- The dose is 500 mg orally tid for 10-14 days (A-I).
- Vancomycin is the drug of choice for an initial episode of severe CDI.
- The dose is 125 mg orally qid for 10-14 days (B-I).
- Vancomycin orally (and per rectum if ileus is present) with or without metronidazole IV is the regimen of choice for the treatment of severe, complicated CDI.
- Vancomycin is dosed at 500 mg qid orally and 500 mg in ~100 mL NS q6h
retention enema. Metronidazole is given at 500 mg q8h IV (C-III).
- Consider colectomy in severely ill patients.
- Monitoring serum lactate and peripheral white blood cell (WBC) count may be helpful in prompting a decision to operate since serum lactate rising to 5 mmol/L
and WBC rising to 50,000 per mL have been associated with greatly increased peri-operative mortality. If surgical management is necessary, carry out a sub-total colectomy with preservation of the rectum (B-II).
- Treatment of the first recurrence is usually with the same
regimen as for the initial episode (A-II) but should be stratified
by disease severity (mild to moderate, severe or severe/complicated) as is recommended for treatment of the initial CDI episode (C-III).
- Do not use metronidazole beyond first recurrence or for
long-term chronic therapy due to potential for cumulative neurotoxicity (B-II).
- Treatment of the second or later recurrence with vancomycin
using a taper and/or pulse regimen is the preferred next
- Currently available probiotics are not recommended to prevent primary CDI since there are limited data to support this approach, and there is a potential risk of blood stream infection (C-III).
Drugs for Oral Therapy
|Agent||How Supplied||Side Effects|
|Metronidazole||250 mg 500 mg||Common: nausea, headache, anorexia, vomiting, diarrhea, epigastric distress, abdominal cramping, constipation Serious: convulsive seizures, peripheral neuropathy|
|Vancomycin||125 mg & 250 mg capsules Alternative: 500 mg/100 mL;|
1 g/200 mL liquid
Recommendations for the Treatment of Clostridium difficile Infection
|Clinical Definition||Supportive Clinical Data||Recommended Treatment|
|Initial episode, mild or moderate||Leukocytosis < 15,000 and creatinine < 1.5X pre-morbid level||Metronidazole 500 mg PO tid|
for 10-14 days
|Initial episode, severe||Leukocytosis ≥ 15,000 or|
creatinine ≥ 1.5X pre-morbid level
|Vancomycin 125 mg PO qid|
for 10-14 days
|Initial episode, complicated||Hypotension or shock,|
|Vancomycin 500 mg qid PO or via NG tube, plus IV metronidazole 500 mg q8h|
If complete ileus: consider adding rectal instillation of vancomycin
|First recurrence||Same as for initial episode|
|Second recurrence||Vancomycin, tapered/pulsed|
Summary of Infection Control Measures for the Prevention of Horizontal Transmission of Clostridium difficile
|Strength of Recommendation|
|Contact Precautions a. Glove use b. Gowns||A-I B-III|
|Private Room or Cohorting||C-III|
|Environmental cleaning, disinfection, or use of disposables a. Replace electronic rectal thermometers with disposables b. Use of hypochlorite (1000-5000 ppm) for disinfection if CDI rates are increased||B-II B-II|