title: Evaluation of ceftobiprole medocaril against Enterococcus faecalis in a mouse peritonitis model.
abstract: OBJECTIVE
  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 beta-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 10 x 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 <or=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.
authors.affiliation: 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.
authors.forename: Cesar A
authors.initials: CA
authors.lastname: Arias
authors.forename: Kavindra V
authors.initials: KV
authors.lastname: Singh
authors.forename: Diana
authors.initials: D
authors.lastname: Panesso
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Murray
mesh_terms: D000668:Ampicillin Resistance; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002511:Cephalosporins / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D013293:Enterococcus faecalis / Q000187:drug effects / Q000201:enzymology; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000201:enzymology / Q000382:microbiology; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D010538:Peritonitis / Q000188:drug therapy* / Q000382:microbiology; D020713:Vancomycin Resistance; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D001618:beta-Lactamases; C505439:ceftobiprole medocaril