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

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, November 2000, p. 3017-3021, Vol. 44, No. 11
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Activity of LY333328 Combined with Gentamicin In Vitro and in Rabbit Experimental Endocarditis Due to Vancomycin-Susceptible or -Resistant Enterococcus faecalis

Agnès Lefort,1 Azzam Saleh-Mghir,1 Louis Garry,1 Claude Carbon,1,2 and Bruno Fantin1,3,*

EMI 9933, Hôpital Bichat-Claude Bernard, Institut National de la Santé et de la Recherche Médicale,1 and Service de Médecine Interne, Hôpital Bichat,2 Paris, and Service de Médecine Interne, Hôpital Beaujon, Clichy,3 France

Received 7 April 2000/Returned for modification 13 June 2000/Accepted 9 August 2000

We investigated the activity of LY333328 alone and combined with gentamicin, both in vitro and in a rabbit model of experimental endocarditis, against the susceptible strain Enterococcus faecalis JH2-2 and its two glycopeptide-resistant transconjugants, BM4316 (VanA) and BM4275 (VanB). MICs of LY333328 and gentamicin were 2 and 16 µg/ml, respectively, for the three strains. In vitro, LY333328 alone was bactericidal at 24 h against JH2-2 at a concentration of 2 µg/ml and against BM4316 and BM4275 at a concentration of 30 µg/ml. The combination of LY333328 and gentamicin (4 µg/ml) was synergistic and bactericidal after 24 h of incubation against the three strains at LY333328 concentrations of 2 µg/ml for JH2-2 and 8 µg/ml for BM4275 and BM4316. The combination of LY333328 and gentamicin was the only regimen demonstrating in vitro bactericidal activity against BM4316. In vivo, intravenous treatment with LY333328 alone, providing peak and trough serum levels of 83.3 ± 1.3 and 3.8 ± 0.2 µg/ml, respectively, was inactive against BM4316 and BM4275 and selected mutants resistant to LY333328 in half of the rabbits infected with the VanA-type strain (MICs, 8 to 20 µg/ml). However, the LY333328-gentamicin combination was active against the three strains and prevented the emergence of mutants resistant to both components of the combination. We conclude that the LY333328-gentamicin combination might be of interest for the treatment of enterococcal infections, particularly against VanA-type strains.

* Corresponding author. Mailing address: Service de Médecine Interne, Hôpital Beaujon, 100, Blvd. du Général Leclerc, 92118 Clichy Cedex, France. Phone: (33) (1) 40 87 58 90. Fax: (33) (1) 40 87 54 95. E-mail: bruno.fantin{at}bjn.ap-hop-paris.fr.

Antimicrobial Agents and Chemotherapy, November 2000, p. 3017-3021, Vol. 44, No. 11
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Belley, A., Neesham-Grenon, E., McKay, G., Arhin, F. F., Harris, R., Beveridge, T., Parr, T. R. Jr., Moeck, G. (2009). Oritavancin Kills Stationary-Phase and Biofilm Staphylococcus aureus Cells In Vitro. Antimicrob. Agents Chemother. 53: 918-925 [Abstract] [Full Text]  
  • Belley, A., Neesham-Grenon, E., Arhin, F. F., McKay, G. A., Parr, T. R. Jr., Moeck, G. (2008). Assessment by Time-Kill Methodology of the Synergistic Effects of Oritavancin in Combination with Other Antimicrobial Agents against Staphylococcus aureus. Antimicrob. Agents Chemother. 52: 3820-3822 [Abstract] [Full Text]  
  • Rouzet, F., Hernandez, M. D., Hervatin, F., Sarda-Mantel, L., Lefort, A., Duval, X., Louedec, L., Fantin, B., Le Guludec, D., Michel, J.-B. (2008). Technetium 99m-Labeled Annexin V Scintigraphy of Platelet Activation in Vegetations of Experimental Endocarditis. Circulation 117: 781-789 [Abstract] [Full Text]  
  • Scapellato, P. G., Ormazabal, C., Scapellato, J. L., Bottaro, E. G. (2005). Meningitis Due to Vancomycin-Resistant Enterococcus faecium Successfully Treated with Combined Intravenous and Intraventricular Chloramphenicol. J. Clin. Microbiol. 43: 3578-3579 [Full Text]  
  • Boylan, C. J., Campanale, K., Iversen, P. W., Phillips, D. L., Zeckel, M. L., Parr, T. R. Jr. (2003). Pharmacodynamics of Oritavancin (LY333328) in a Neutropenic-Mouse Thigh Model of Staphylococcus aureus Infection. Antimicrob. Agents Chemother. 47: 1700-1706 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»