Updated 2017 Clostridium difficile Infection Guideline

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July 31, 2018 by dailybolusoflr

By: Jason Kurian, PharmD

The IDSA/SHEA Clostridium difficile infection (CDI) 2017 Guideline is an update from the previous version published in 2010.


CDI is defined by the presence of symptoms and either a positive stool test for C. difficile or colonoscopic/histopathologic finding of pseudomembranous colitis. Due to the limitations of stool tests such as the nucleic acid amplification test (NAAT) to differentiate between those colonized and actively infected with C. difficile, appropriate selection of those patients likely to have an active CDI is important. The preferred population for CDI testing are those with unexplained and new-onset > 3 unformed stools in 24 hours. If the patient has not stooled in the last 24 hours, it is unlikely the patient has CDI.


The previous guideline used severity criteria that were based on expert opinion to guide the choice of antibiotic, metronidazole or vancomycin, to initiate for treatment of CDI. However, metronidazole is no longer recommended as first-line therapy in adults due to data showing delayed treatment response and worse clinical cure rates with metronidazole over vancomycin. Instead oral vancomycin or fidaxomicin are recommended as first-line therapy in both non-severe and severe CDI. In cases of fulminant CDI, oral vancomycin at a higher dose with the addition of parenteral metronidazole are recommended. Addition of vancomycin given as a rectal retention enema should be initiated if an ileus is present. At JHH, fidaxomicin is formulary restricted to approval by the Antimicrobial Stewardship Program at all times

Recommended treatment strategies for recurrent CDI include the standard 10-day course of oral vancomycin if metronidazole was used for treatment of the initial CDI episode. If the standard oral vancomycin regimen was used for the initial CDI episode, either a prolonged tapered and pulsed oral vancomycin regimen (see Table 1) or fidaxomicin should be used. Recommendations for subsequent CDI recurrences include a prolonged tapered and pulsed oral vancomycin regimen, a standard 10-day course of oral vancomycin followed by rifaximin, or fecal microbiota transplantation.

Ancillary treatments include discontinuing the inciting antibiotic agent as soon as possible if present.


The guideline continues to recommend WBC count and serum creatinine as supportive clinical data for the classification of severe CDI but have changed the creatinine value to an absolute value as opposed to the previous 50% increase from baseline value, which are not always available. The guideline does acknowledge that this criteria does not perform well for patients with underlying hematologic malignancies or renal insufficiency.


The guideline provides a strong recommendation to minimize the frequency and duration of high-risk antibiotic therapy and the number of antibiotic agents to reduce CDI risk. High-risk antibiotics include fluoroquinolones, clindamycin, and 3rd/4th generation cephalosporins such as ceftriaxone and cefepime. Even very limited exposure, such as single-dose surgical antibiotic prophylaxis, increases a patient’s risk of C. difficile colonization and symptomatic disease. Additionally, there is an epidemiologic association between proton pump inhibitor (PPI) use and CDI therefore unnecessary PPIs should be discontinued. However, a causal relationship remains unclear.




Table 1. Summary of Guideline Recommendations for Treatment of CDI in Adults

Clinical Definition Supportive Clinical Data Treatment
Initial episode, non-severe WBC < 15,000 cells/mL AND

SCr < 1.5 mg/dL

·   VAN 125 mg PO 4x daily x 10 days OR

·   FDX 200 mg PO BID x 10 days

·   If above agents are unavailable, metronidazole 500 mg PO TID x 10 days

Initial episode, severe WBC > 15,000 cells/mL OR

SCr > 1.5 mg/dL

·   VAN 125 mg PO 4x daily x 10 days OR

·   FDX 200 mg PO BID x 10 days

Initial episode, fulminant Hypotension or shock, ileus, megacolon ·   VAN 500 mg PO 4x daily + metronidazole 500 mg IV q8h

·   If ileus, can add VAN 500 mg per rectum q6h as a retention enema

First recurrence ·   VAN 125 mg PO 4x daily x 10 days if metronidazole was used for the initial episode OR

·   Prolonged tapered and pulsed VAN regimen* if a standard regimen was used for the initial episode OR

·   FDX 200 mg PO BID x 10 days if VAN was used for the initial episode

Second or subsequent recurrence ·   VAN in a tapered and pulsed regimen* OR

·   VAN 125 mg PO 4 x daily followed by rifaximin 400 mg TID x 20 days OR

·   FDX 200 mg PO BID x 10 days OR

·   Fecal microbiota transplantation^

VAN: Vancomycin; Fidaxomicin: FDX

*Vancomycin 125 mg PO 4x daily x 10-14 days, then BID x 7 days, then every 2-3 days for 2-8 weeks

^Recommended for patients with multiple recurrences of CDI who have failed appropriate antibiotic treatments



  1. McDonald LC, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):e1-e48.
  2. Privitera G, et al. Prospective study of Clostridium difficile intestinal colonization and disease following single-dose antibiotic prophylaxis in surgery. Antimicrob Agents Chemother. 1991; 35:208–10.

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