Evaluation of ceftobiprole in a rabbit model of aortic valve endocarditis due to methicillin-resistant and vancomycin-intermediate Staphylococcus aureus

Abstract

Ceftobiprole is a novel broad-spectrum cephalosporin that binds with high affinity to PBP 2a, the methicillin-resistance determinant of staphylococci, and is active against methicillin- and vancomycin-resistant Staphylococcus aureus. Ceftobiprole was compared to vancomycin in a rabbit model of methicillin-resistant S. aureus aortic valve endocarditis. Ceftobiprole and vancomycin were equally effective against endocarditis caused by methicillin-resistant S. aureus strain 76, whereas ceftobiprole was more effective than vancomycin against the vancomycin-intermediate S. aureus strain HIP5836. The activity of ceftobiprole against drug-resistant strains of S. aureus warrants its further clinical development.

FIG. 1.

Structures of ceftobiprole and its dioxolenylmethyl carbamate prodrug, ceftobiprole medocaril.

FIG. 2.

Time-kill studies of MRSA strain 76 comparing ceftobiprole at 1 and 5 μg/ml (BPR 1 and BPR 5, respectively) with vancomycin at 10 μg/ml (Van 10) and nafcillin at 32 μg/ml (Naf 32).

FIG. 3.

Time-kill studies of VISA strain HIP5836 comparing ceftobiprole at 1 and 5 μg/ml (BPR 1 and BPR 5, respectively) with vancomycin at 10 μg/ml (Van 10) and nafcillin at 32 μg/ml (Naf 32).

FIG. 4.

Survival curves for rabbits with endocarditis caused by MRSA strain 76, comparing treatment with ceftobiprole to treatment with vancomycin (Vanco).

FIG. 5.

Survival curves for rabbits with endocarditis caused by VISA strain HIP5836, comparing treatment with ceftobiprole to treatment with vancomycin (Vanco).