Rifaximin therapy for metronidazole-unresponsive Clostridium difficile infection: a prospective pilot trial

Abstract

Abstract:Background: Clostridium difficile infection (CDI) is a recent epidemic in the United States, particularly in the hospital setting. Oral metronidazole is standard therapy for C. difficile infection, but resistance to metronidazole is becoming a clinical challenge. Methods: We evaluated the efficacy of the nonsystemic oral antibiotic rifaximin for the treatment of metronidazole-resistant C. difficile infection. Twenty-five patients with C. difficile infection were enrolled in the study. All had mild-to-moderate C. difficile infection (510 bowel movements a day without sepsis) unresponsive to metronidazole (i.e. stools positive for toxins A and B after oral metronidazole 500 mg three times daily [t.i.d.] for 5 days). After discontinuation of metronidazole, rifaximin 400 mg t.i.d. for 14 days was prescribed. Patients were followed for 56 days and stool was tested for C. difficile using polymerase chain reaction (PCR) to assess the effect of treatment. A negative PCR test result was interpreted as a favorable response to rifaximin. Results: Sixteen of 22 patients (73%) were eligible for study inclusion and completed rifaximin therapy experienced eradication of infection (stool negative for C. difficile) immediately after rifaximin therapy and 56 days post-treatment. Three patients (12%) discontinued therapy because of abdominal distention. Rifaximin was generally well tolerated. Conclusions: In conclusion, rifaximin may be considered for treatment of mild-to-moderate C. difficile infection that is resistant to metronidazole. Larger randomized trials are needed to confirm these positive findings.

Treatment of recurrent Clostridium difficile infection: a systematic review

“…Several other antibiotics have been examined, particularly nitazoxanide [18, 28], rifaximin [29–35], and fidaxomicin [19, 20]. Nitazoxanide is a thiazoline-class antibiotic developed primarily as an anti-parasitic agent.…”

“…Seven publications report the use of rifaximin in treating RCDI, including two case reports [29, 30], three case series [31–34], and one prospective trial [35]. These total 49 patients, and report an aggregate of 12 failures.…”

Lack of Clostridium difficile Infection in Patients Treated With Rifaximin for Hepatic Encephalopathy

“…10,11 Several reports have demonstrated the efficacy of rifaximin in the treatment of CDI, including CDI that is refractory to standard therapies (ie, metronidazole or vancomycin). [14][15][16][17][18][19][20][21] In addition, a Cochrane Database systematic review established that the efficacy of rifaximin for the treatment of CDI was similar to that observed with vancomycin. 22 Rifaximin also reduced the risk of breakthrough HE and of hospitalizations for HE in patients in remission from HE compared with placebo in a large phase 3 clinical trial 23 and has equal or greater efficacy than systemic antibiotics or nonabsorbable disaccharides used for the treatment of HE.…”

Antibiotics and Inflammatory Bowel Diseases

“…However, a case of C. difficile infection was reported in a patient on rifaximin 800 mg twice daily, 20 days after the end of the treatment period. Although rifaximin has been successfully employed in the treatment of C. difficile infection in metronidazole-unresponsive patients, it is probable that rare clones of rifaximin-resistant C. difficile can arise [49]. …”