This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kokkotou, E. Articles by Kelly, C. P. Search for Related Content PubMed PubMed Citation Articles by Kokkotou, E. Articles by Kelly, C. P.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, March 2008, p. 1121-1126, Vol. 52, No. 3
0066-4804/08/$08.00+0     doi:10.1128/AAC.01143-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Comparative Efficacies of Rifaximin and Vancomycin for Treatment of Clostridium difficile-Associated Diarrhea and Prevention of Disease Recurrence in Hamsters

Efi Kokkotou,¹ Alan C. Moss,¹ Athanasios Michos,¹ Daniel Espinoza,¹ Jeffrey W. Cloud,¹ Nasima Mustafa,¹ Michael O'Brien,² Charalabos Pothoulakis,¹ and Ciarán P. Kelly^1*

Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts,¹ Mallory Institute and Department of Pathology, Boston University Medical Center, Boston, Massachusetts²

Received 28 August 2007/ Returned for modification 4 December 2007/ Accepted 3 January 2008

Clostridium difficile-associated colitis is an increasing cause of morbidity and mortality in hospitalized patients, with high relapse rates following conventional therapy. We sought to determine the efficacy of rifaximin, a novel nonabsorbed antibiotic, in the hamster model of C. difficile-associated diarrhea (CDAD). Hamsters received clindamycin subcutaneously and 24 h later were infected by gavage with one of two C. difficile strains: a reference strain (VPI 10463) and a current epidemic strain (BI17). Vancomycin (50 mg/kg of body weight) or rifaximin (100, 50, and 25 mg/kg) were then administered orally for 5 days beginning either on the same day as infection (prevention) or 24 h later (treatment). Therapeutic effects were assessed by weight gain, histology, and survival. We found that rifaximin was as effective as vancomycin in the prevention and treatment of colitis associated with the two C. difficile strains that we examined. There was no relapse after treatment with vancomycin or rifaximin in hamsters infected with the BI17 strain. Hamsters infected with the VPI 10463 strain and treated with rifaximin did not develop relapsing infection within a month of follow-up, whereas the majority of vancomycin-treated animals relapsed (0% versus 75%, respectively; P < 0.01). In conclusion, rifaximin was found to be an effective prophylactic and therapeutic agent for CDAD in hamsters and was not associated with disease recurrence. These findings, in conjunction with the pharmacokinetic and safety profiles of rifaximin, suggest that it is an attractive candidate for clinical use for CDAD.

---

* Corresponding author. Mailing address: Division of Gastroenterology, Dana 601/East Campus, Beth Israel Deaconess Medical Center, Boston MA 02215. Phone: (617) 667-1264. Fax: (617) 975-5071. E-mail: ckelly2{at}bidmc.harvard.edu

Published ahead of print on 14 January 2008.

---

Antimicrobial Agents and Chemotherapy, March 2008, p. 1121-1126, Vol. 52, No. 3
0066-4804/08/$08.00+0     doi:10.1128/AAC.01143-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Williams, O. M., Spencer, R. C. (2009). The management of Clostridium difficile infection. Br Med Bull 91: 87-110 [Abstract] [Full Text]  
• Ochsner, U. A., Bell, S. J., O'Leary, A. L., Hoang, T., Stone, K. C., Young, C. L., Critchley, I. A., Janjic, N. (2009). Inhibitory effect of REP3123 on toxin and spore formation in Clostridium difficile, and in vivo efficacy in a hamster gastrointestinal infection model. J Antimicrob Chemother 63: 964-971 [Abstract] [Full Text]