MPA | Pharmacy News

By Carly Burns, Pharm.D. candidate 2019 and Jamie George, Pharm.D. candidate 2019, Wayne State University Eugene Applebaum College of Pharmacy and Health Sciences, Detroit

Clostridium difficile infection (CDI) has become the leading cause of nosocomial infection in the United States. Treatment of CDI is costly, and unfortunately, incidence is projected to increase in both the inpatient and outpatient care settings.1,2

C. difficile is transmitted via the fecal-oral route or direct exposure, often by the hands of healthcare workers. In vulnerable individuals, the bacteria can produce two exotoxins (A and B) and cause colitis.2,3 Individuals most at risk of developing infection include those with recent or current antibiotic use, hospital exposure and age greater than 65.3 Prevention of CDI is routed in antibiotic stewardship and appropriate hand hygiene in healthcare personnel. Hand washing with soap and water is preferred over alcohol rubs, as alcohol fails to eliminate spores.2

The gold standard to diagnose CDI involves laboratory fecal testing. These steps should be considered in patients with new-onset diarrhea for whom there is no alternative cause.4 CDI is categorized by the severity of illness. Severe CDI is classified as the presence of leukocytosis (white blood cell count of >15,000 cells/mL) or a serum creatinine level of greater than 1.5 mg/dL (with non-severe CDI failing to meet these criteria). Fulminant CDI is the presence of shock/hypotension, ileus or toxic megacolon.4

Historically, metronidazole was utilized as first-line treatment for CDI due to lower costs and concerns of vancomycin-resistant organisms. However, metronidazole is no longer recommended as initial single-agent therapy in the recent 2017 Infectious Diseases Society of America (IDSA) guideline. This change in practice is based upon numerous trials published since the early 2000s where oral vancomycin was found to be superior to metronidazole in terms of clinical cure and diarrhea resolution.4 One trial conducted by Zar et al. found clinical cure was achieved in only 76 percent of patients receiving metronidazole compared to 97 percent in those receiving vancomycin. A pooled analysis demonstrated increased recurrence of CDI with metronidazole 30 days following treatment completion.5 Increased rates of metronidazole resistance may be in part responsible for these findings. An additional theory takes into consideration the pharmacokinetic profile of the two antibiotics.6 Vancomycin is minimally absorbed into systemic circulation following oral administration and maintains consistently high concentrations in the feces, compared to metronidazole which achieves low fecal concentrations.6

Table 1 delineates the key points of the new CDI treatment recommendations according to the updated IDSA guidelines. Development of new CDI treatments continues to gain considerable interest. Several strategies, including the development of a C. difficile vaccine, are currently undergoing clinical trials due to the increasing incidence of disease and emerging resistance to standard of care.7

Table 1. Treatment for CDI in adult patients4.


Treatment Recommendation

Strength of Recommendation/ Quality of Evidence

Initial Presentation


Non-severe and Severe CDI

Fulminant CDI

  • Vancomycin PO 125mg four times daily x 10 days 


  • Fidaxomicin PO 200mg twice daily x 10 days
  • Vancomycin PO 500mg four times daily +/- Parenteral metronidazole

o Rectal administration for patients with ileus







Recurrent CDI


Determined by initial antibiotic used

  • Metronidazole initially: Retreat with vancomycin
  • Vancomycin initially:

o Tapered and pulsed regimen of Vancomycin 


o Fidaxomicin







Multiple Recurrent CDI

Same as recurrent CDI in addition to:

  • Vancomycin PO x 10 days followed by a 20-day course of rifaximin
  • Fidaxomicin
  • Fecal transplantation







  1. Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile Infection in the United States. N Engl J Med. 2015; 372:825-834.
  2. Centers for Disease Control and Prevention. Health Care Associated Infections. CDC website. Updated Sept. 23, 2015. Accessed Aug. 12, 2018.
  3. Leffler DA, and Lamont JT. Clostridium difficile Infection. N Engl J Med. 2015; 372:1539-1548.
  4. McDonald LC, Gerding DN, Johnson S, 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;66(7):e1–e48.
  5. Zar FA, Bakkanagari SR, Moorthi K, et al. A Comparison of Vancomycin and Metronidazole for the Treatment of Clostridium difficile–Associated Diarrhea, Stratified by Disease Severity. Clin Infect Dis. 2007;45(3):302-307.
  6. Chahine EB. The Rise and Fall of Metronidazole for Clostridium difficile Infection. Ann Pharmacother. 2018;52(6):600–602.
  7. Peng Z, Ling L, Stratton CW, et al. Advances in the diagnosis and treatment of Clostridium difficile infections. Emerg Microbes Infect. 2018;7(1):15.

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