Efficacies of ceftobiprole medocaril and comparators in a rabbit model of osteomyelitis due to methicillin-resistant Staphylococcus aureus.
The pharmacokinetics and distribution into bone tissue of ceftobiprole in uninfected New Zealand White rabbits were determined after subcutaneous administration of the prodrug ceftobiprole medocaril. Serum exposure (maximum concentration of the drug in serum, trough concentration, area under the concentration-time curve) to ceftobiprole at 20 and 80 mg/kg was dose proportional, and there was no accumulation of ceftobiprole following repeated (every 6 h [q6h]) injections of the antibiotic. Ceftobiprole titers in the tibial matrix and marrow were 3.2 +/- 1.3 microg/g and 11.2 +/- 6.5 microg/g, respectively, in uninfected animals treated with 20 mg/kg of the antibiotic and 13.4 +/- 7.3 microg/g and 66.3 +/- 43.2 microg/g, respectively, in uninfected animals treated with 80 mg/kg of the antibiotic. No differences in ceftobiprole titers were observed between right and left tibiae for either bone matrix or marrow. The efficacies of 4 weeks of treatment with ceftobiprole (40 mg/kg administered subcutaneously [s.c.] q6h), vancomycin (30 mg/kg administered s.c. q12h), or linezolid (60 mg/kg administered orally q8h) were compared, using a rabbit model of methicillin-resistant Staphylococcus aureus tibial osteomyelitis. After treatment with ceftobiprole, the bacterial titers in all infected left tibiae from evaluable rabbits were below the level of detection, whereas only 73% of infected left tibiae from vancomycin- or linezolid-treated animals had bacterial titers below the level of detection; the mean titers of ceftobiprole were 3 to 5 times higher in infected left tibiae than in uninfected right tibiae. These results indicate that ceftobiprole provided effective parenteral treatment of osteomyelitis in this rabbit model.
Yin
Li-Yan
LY
Department of Orthopaedic Surgery, University of Missouri, One Hospital Drive, Columbia, Missouri 65212, USA.
Calhoun
Jason H
JH
Thomas
Jacob K
JK
Shapiro
Stuart
S
Schmitt-Hoffmann
Anne
A
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002511:Cephalosporins / Q000493:pharmacokinetics / Q000494:pharmacology*; D004195:Disease Models, Animal; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D010019:Osteomyelitis / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects*; D013977:Tibia / Q000187:drug effects / Q000382:microbiology / Q000473:pathology
D002511:Cephalosporins; C505439:ceftobiprole medocaril