This patient with a second recurrence of mild to moderate Clostridium difficile infection (CDI) should be treated with oral vancomycin for 6 weeks. Approximately 20% of patients with CDI will experience a relapse. In 2010, an expert panel outlined evidence-based recommendations for treatment of CDI. A recent study found that adherence to these guidelines resulted in significantly improved outcomes and fewer recurrences of CDI.

The initial treatment regimen is based on the severity of illness, with a 10- to 14-day course of oral metronidazole recommended for mild to moderate illness and a 10- to 14-day course of oral vancomycin for severe illness. For the first recurrence, guidelines specify that treatment decisions should be based on the severity of illness, similar to the determination of appropriate treatment with the initial presentation. However, for subsequent relapses, the probability of sustained response is significantly decreased, and it is therefore recommend that all patients receive a prolonged course of vancomycin, typically given at tapered doses over 6 to 8 weeks.

Metronidazole is not recommended for use in multiple recurrences of CDI because prolonged administration is associated with a risk for neurotoxicity, and luminal concentrations of the antibiotic decrease to subtherapeutic levels after resolution of colitis.

Small studies have suggested that rifaximin may be useful in multiple recurrences of CDI when given at the end of the vancomycin taper, but this agent is not recommended as a stand-alone therapy.