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Antimicrobial Agents and Chemotherapy, June 2004, p. 2144-2148, Vol. 48, No. 6
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.6.2144-2148.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Efficacy of Oral Ramoplanin for Inhibition of Intestinal Colonization by Vancomycin-Resistant Enterococci in Mice

Usha Stiefel,1 Nicole J. Pultz,2 Marion S. Helfand,2 and Curtis J. Donskey2*

Division of Infectious Diseases, University Hospitals of Cleveland,1 Research Section, Louis Stokes Cleveland Veterans Affairs Medical Center, Case Western Reserve University, Cleveland, Ohio 441062

Received 4 February 2004/ Returned for modification 12 February 2004/ Accepted 25 February 2004

Ramoplanin is a glycolipodepsipeptide antibiotic with activity against gram-positive bacteria that is in clinical trials for prevention of vancomycin-resistant Enterococcus (VRE) bloodstream infections and treatment of Clostridium difficile diarrhea. Orally administered ramoplanin suppresses VRE intestinal colonization, but recurrences after discontinuation of treatment have frequently been observed. We used a mouse model to examine the efficacy of ramoplanin for inhibition of VRE colonization and evaluated the etiology of recurrences of colonization. Eight days of treatment with ramoplanin (100 µg/ml) in drinking water suppressed VRE to undetectable levels, but 100% of mice developed recurrent colonization; a higher dose of 500 µg/ml in water was associated with recurrent colonization in 50% of mice. Two of eight (25%) mice treated with the 100-µg/ml dose of ramoplanin had low levels of VRE in their cecal tissues on day 8 despite undetectable levels in stool and cecal contents. Mice that received prior ramoplanin treatment did not develop VRE overgrowth when challenged with 107 CFU of oral VRE 1, 2, or 4 days later. In communal cages, rapid cross-transmission and overgrowth of VRE was observed among clindamycin-treated mice; ramoplanin treatment effectively suppressed VRE overgrowth in such communal cages. Ramoplanin treatment promoted increased density of indigenous Enterobacteriaceae and overgrowth of an exogenously administered Klebsiella pneumoniae isolate. These results demonstrate the efficacy of ramoplanin for inhibition of VRE colonization and suggest that some recurrences occur due to reexpansion of organisms that persist within the lining of the colon. Ramoplanin treatment may be associated with overgrowth of gram-negative bacilli.

* Corresponding author. Mailing address: Infectious Diseases Section, Louis Stokes Cleveland Veterans Affairs Medical Center, 10701 East Blvd., Cleveland, OH 44106. Phone: (216) 791-3800, ext. 5103. Fax: (216) 229-8509. E-mail: curtisd123{at}yahoo.com.

Antimicrobial Agents and Chemotherapy, June 2004, p. 2144-2148, Vol. 48, No. 6
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.6.2144-2148.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Li, L., Redding, S., Dongari-Bagtzoglou, A. (2007). Candida glabrata, an Emerging Oral Opportunistic Pathogen. JDR 86: 204-215 [Abstract] [Full Text]  
  • Paterson, D. L., Stiefel, U., Donskey, C. J. (2006). Effect of a Selective Decontamination of the Digestive Tract Regimen Including Parenteral Cefepime on Establishment of Intestinal Colonization with Vancomycin-Resistant Enterococcus spp. and Klebsiella pneumoniae in Mice.. Antimicrob. Agents Chemother. 50: 2537-2540 [Abstract] [Full Text]  
  • Freeman, J., Baines, S. D., Jabes, D., Wilcox, M. H. (2005). Comparison of the efficacy of ramoplanin and vancomycin in both in vitro and in vivo models of clindamycin-induced Clostridium difficile infection. J Antimicrob Chemother 56: 717-725 [Abstract] [Full Text]  
  • Farver, D. K, Hedge, D. D, Lee, S. C (2005). Ramoplanin: A Lipoglycodepsipeptide Antibiotic. The Annals of Pharmacotherapy 39: 863-868 [Abstract] [Full Text]  


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