JAC Advance Access published online on July 2, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm237
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Evaluation of ceftobiprole medocaril against Enterococcus faecalis in a mouse peritonitis model
1 Center for the Study of Emerging and Reemerging Pathogens, Division of Infectious Diseases, University of Texas Medical School at Houston, 6431 Fannin Street, MSB 2.112, Houston, TX 77030, USA 2 Department of Internal Medicine, University of Texas Medical School at Houston, 6431 Fannin Street, MSB 2.112, Houston, TX 77030, USA 3 Molecular Genetics and Antimicrobial Resistance Unit, Universidad El Bosque, Transv 9a No. 133-25, Bogota, Colombia 4 Department of Microbiology and Molecular Genetics, University of Texas Medical School at Houston, 6431 Fannin Street, MSB 2.112, Houston, TX 77030, USA
Received 23 April 2007; returned 10 May 2007; revised 5 June 2007; accepted 6 June 2007
* Corresponding author. Tel: +1-713-500-6745; Fax: +1-713-500-6766; E-mail: bem.asst{at}uth.tmc.edu
Objectives: Ceftobiprole is a novel broad-spectrum cephalosporin with good in vitro activity against methicillin-resistant Staphylococcus aureus and Enterococcus faecalis. The objective of this study was to assess the in vivo activity of ceftobiprole against four strains of E. faecalis, including ß-lactamase- producing (Bla+) and vancomycin-resistant strains.
Methods: Mice were infected intraperitoneally with strains of E. faecalis: (i) the Bla+ strain HH22; (ii) two vancomycin-resistant strains (TX2484 and V583); and (iii) OG1RF (a laboratory strain), using 10x the LD50 for each strain. Ceftobiprole doses of 25, 12.5 and 6.25 mg/kg (single doses) and ampicillin 50, 25, 12.5 and 6.25 mg/kg (single and double doses) were administered subcutaneously immediately after bacterial challenge and mice were monitored for 96 h.
Results: All four E. faecalis had ceftobiprole MICs 
0.5 mg/L. Despite being susceptible in vitro at the standard inoculum, ampicillin (single and double doses) did not protect mice against intraperitoneal challenge with Bla+ E. faecalis HH22, with a 50% protective dose (PD50) of >100 mg/kg, whereas ceftobiprole was protective (PD50 of 2 mg/kg). Ceftobiprole PD50s for vancomycin-resistant isolates TX2484 and V583 were 7.7 and 5.2 mg/kg, respectively, similar to those of single dose ampicillin (12.5 and 16.4 mg/kg, respectively). For OG1RF, both ampicillin and ceftobiprole protected all mice at doses of 25 and 12.5 mg/kg, respectively, with a PD50 of 4.2 and 8 mg/kg for ceftobiprole and ampicillin, respectively.
Conclusions: Ceftobiprole had comparable in vivo activity to that of ampicillin against vancomycin-resistant and ampicillin-susceptible strains of E. faecalis in the mouse peritonitis model. Ceftobiprole was superior in vivo to ampicillin against the Bla+ strain HH22. Our data support the further study of ceftobiprole as a therapeutic agent in humans infected with E. faecalis.
Key Words: enterococci , cephalosporins , animal model
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. D Anderson and J. G Gums Ceftobiprole: An Extended-Spectrum Anti-Methicillin-Resistant Staphylococcus aureus Cephalosporin Ann. Pharmacother., June 1, 2008; 42(6): 806 - 816. [Abstract] [Full Text] [PDF]
|
|