Intravenous Immunoglobulin for the Treatment of Severe, Refractory, and Recurrent Clostridium difficile Diarrhea

PURPOSE: Clostridium difficile diarrhea is common in elderly patients and leads to prolonged hospitalization. Patients with severe or recurrent Clostridium difficile diarrhea have poor antitoxin antibody responses. Intravenous immunoglobulin has been advocated in these patients. This study was designed to assess the response of patients with refractory, recurrent, or severe Clostridium difficile diarrhea to intravenous immunoglobulin. METHODS: Retrospective review (November 2003-January 2005) of 14 patients with severe, refractory, recurrent Clostridium difficile diarrhea treated with intravenous immunoglobulin (Flebogamma, 150-400 mg/kg) from 264 Clostridium difficile toxin-positive patients. RESULTS: Median age was 79 (range, 54-91) years. Median length of symptoms before intravenous immunoglobulin was 29 (range, 3-90) days. Patients received a median of three (range, 1-5) courses of vancomycin or metronidazole before intravenous immunoglobulin. All had hypoalbuminemia (median, 22 g/l; range, 18-33) and raised C-reactive protein (median, 47 mg/l; range, 25-255) at time of infusion. The median white cell count was 15.3 x 10(9)/liters (range, 4-24). Eight patients had evidence of pancolitis on abdominal imaging, suggesting severe Clostridium difficile diarrhea. All patients tolerated intravenous immunoglobulin without side effects. Nine (64 percent) responded with bowels normalizing in a median of ten (range, 2-26) days; one patient received two doses. One patient had a partial response from two doses but died two months later after a recurrence. The other four patients died of other causes within three weeks of infusion. CONCLUSIONS: Intravenous immunoglobulin may be effective for severe, refractory, or recurrent Clostridium difficile diarrhea after failed conventional treatment.