Clostridium difficile infections (CDIs) have increased and become more resistant to treatment since the emergence of the epidemic BI/NAP1/027 strain of C. difficile in 2000. A review in the Journal of the American Medical Association reviewed 116 studies published from January 1978 to October 31, 2014 on diagnostic testing and treatment of CDIs in adults ≥18 years.

Because laboratory testing alone cannot distinguish between asymptomatic colonization and clinical symptoms of infection, diagnosis requires presence of diarrhea (≥3 unformed stools in 24 hours) or radiographic evidence of ileus or toxic megacolon plus a positive stool test result for toxigenic C difficile or its toxins, or colonoscopic or histopathologic findings demonstrating pseudomembranous colitis. Chronic shedding of spores can occur for as long as six weeks, so a test of cure is not recommended.

Clinical manifestations of CDI can range from mild diarrhea to life-threatening illness, so it should be treated according to disease severity and risk of recurrence and complications. Earlier studies suggested that oral metronidazole and oral vancomycin had similar efficacy, tolerability, and relapse rates but newer data suggests that metronidazole may have greater treatment failure rates when used in severe or complicated CDI. Thus, oral metronidazole or vancomycin are recommended for the first recurrence of mild to moderate CDI and vancomycin for patients with ≥2 recurrences. If the risk of recurrence is high or for recurrent CDI, fidaxomicin may be considered. While evidence suggests that probiotics may prevent initial episodes and recurrence, their role in preventing initial episodes is poorly defined. Fecal microbiota transplantation has shown positive clinical response without reports of adverse events for refractory or recurrent CDI but the FDA considers this treatment to be investigational.