Rifaximin has FDA approval for indications other than CDI but has also been used to treat CDI. Rifaximin was compared with vancomycin in a small study (20 patients) that showed comparable cure rates. Recently, rifaximin has been used as an adjunct agent to treat patients with multiple CDI recurrences. We used a 2‐week course of rifaximin (usually at 400 mg twice a day) immediately following the last course of vancomycin treatment (the “rifaximin chaser”) for a group of patients who had a mean of 6 recurrences within 1–2 weeks after stopping treatment for the previous episode. With this approach, there were no additional recurrences in 11 (79%) of 14 patients who had recurrent CDI. Garey et al took a different approach and used rifaximin to treat the symptomatic CDI episode and continued rifaximin for a total of 4 weeks (at 400 mg 3 times a day for 2 weeks, followed by 200 mg 3 times a day for 2 weeks). Five of the 6 rifaximin‐treated patients had no additional episodes. One caution in using rifaximin is the increasing recognition of clinical C. difficile isolates with high‐level resistance (minimum inhibitory concentration [MIC] values, >256 μg/mL), including isolates from 2 of the 3 patients whose “rifaximin chaser” protocol failed. Widespread dissemination of these strains or prior CDI treatment with rifaximin may limit its efficacy. Another rifamycin, rifampin, has been used successfully when coadministered with vancomycin in a small group of patients with recurrent CDI. A more recent randomized study of rifampin coadministered with metronidazole for treatment of a primary episode of CDI demonstrated no benefit from the addition of rifampin. Treatment with metronidazole plus rifampin and treatment with metronidazole alone had similar cure rates (63% vs 65%) and recurrence rates (42% vs 38%). There were more deaths in the group given metronidazole plus rifampin, although only 1 of the 6 deaths was attributed to CDI.
Nitazoxanide, FDA approved for treatment of giardiasis and cryptosporidiosis, interferes with the anaerobic metabolism of some bacteria, as well as protozoa, and has been compared to both metronidazole and vancomycin for the treatment of CDI. Musher et al compared nitazoxanide at 2 durations to metronidazole in a prospective, randomized, double‐blinded study involving 142 patients with CDI. Nitazoxanide (at 500 mg twice a day for 10 days or 500 mg twice a day for 7 days) was at least as effective as metronidazole (at 250 mg 4 times a day for 10 days), with similar response rates (90% vs 82%) and recurrence rates (18% vs 23%). Nitazoxanide was also effective in patients who had failed to respond to metronidazole or who had recurrence after successful treatment with metronidazole. In a smaller randomized comparison of nitazoxanide with vancomycin (involving 50 patients), results were similar, but because of the small sample size, noninferiority could not be established.