Emerging Therapies in the Treatment of Clostridium difficile-Associated Disease

Tomasz Z. Jodlowski, PharmD; Richard Oehler, MD; Linda W. Kam, PharmD BCPS; Igor Melnychuk, MD

Disclosures

The Annals of Pharmacotherapy. 2006;40(12):2164-2169. 

In This Article

Rifaximin

Rifaximin is a semisynthetic analog of the rifamycin antimicrobial rifampin. The addition of a benzimidazole ring makes rifaximin essentially nonabsorbed (bioavailability <0.4%); hence, its usefulness for treatment of intraabdominal infections. The Food and Drug Administration (FDA) approved this agent for the treatment of travelers' diarrhea caused by noninvasive strains of Escherichia coli in patients who are 12 years of age or older. Rifaximin has been used in Italy since 1987 for the treatment of various infections. It has also been useful in hepatic encephalopathy, as well as in pre- and postsurgical prophylaxis.[14,15] This drug exerts its activity by inhibiting the initiation of RNA synthesis by binding to the ß subunit of the RNA polymerase.[14]

In vitro, the minimum inhibitory concentration (MIC) values of C. difficile are among the lowest of any enteric pathogen for rifaximin. Gerard et al.[14] identified one study in which 34 of 56 clinical isolates of C. difficile were inhibited by rifaximin at a concentration of 0.78 µg/mL, with the remainder inhibited at concentrations greater than 25 µg/mL. Although the interpretation of these MIC results is difficult in the absence of known gastrointestinal concentrations, it is likely that the drug concentration achieved at the site of action would largely exceed the reported MIC values. Fecal levels after oral administration of the agent have been shown to range from 4000 to 8000 µg/g of stool.[15] In addition, the microorganism shows a particularly low incidence of spontaneously resistant mutants (<1 × 10-9), which could prove useful in treating the emergent strain.

In an open-label study, Boero et al.[16] compared rifaximin 200 mg 3 times daily for 10 days with oral vancomycin 500 mg twice daily for 10 days (N = 20). Time to toxin disappearance ± SD was significantly shorter with vancomycin, at 4.8 ± 1.48 days, versus rifaximin, at 8.1 ± 1.79 days (p < 0.005). Time to stool normalization was similar with vancomycin, at 3.8 ± 1.48 days, versus rifaximin, at 4.9 ± 2.38 days (p = NS). Overall, rifaximin was found to be effective in 9 of 10 patients, while vancomycin was successful in all 10 patients who received it.

We have identified several cases in our practice in which rifaximin wassuccessfully used for CDAD when other agents failed or were contraindicated,but more supportive evidence is needed. Overall, rifaximin appears to be avalid alternative for the treatment and management of CDAD, although further,larger studies are needed to clearly define its role.

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