Management of patients with Clostridium difficile infection (CDI) can be very difficult, especially for the approximately 25% of patients who have had recurrences, and particularly for those who have had multiple recurrences. Following recurrence, patients typically respond to a new course of antimicrobial treatment, usually with vancomycin or fidaxomicin, but often have another recurrence within a few days to months after stopping treatment. Although treatment failure to resolve symptoms is not uncommon when metronidazole is used,1 failure to resolve symptoms when treated with a new course of antimicrobial treatment with either vancomycin or fidaxomicin is an indication that a condition other than CDI may be the cause of the patient's symptoms.