Ceftobiprole: in-vivo profile of a bactericidal cephalosporin

Abstract

Resistance to antimicrobials is a significant and growing problem, limiting treatment options, especially for serious Gram-positive infections. Ceftobiprole is a novel broad-spectrum cephalosporin that is active in vitro against streptococci and staphylococci, including penicillin-resistant strains of pneumococci and methicillin-resistant Staphylococcus aureus (MRSA). It maintains the activity of extended-spectrum cephalosporins against Gram-negative bacteria, including Enterobacteriaceae. The in-vivo activity of ceftobiprole has been demonstrated in mouse sepsis and subcutaneous abscess models of infection. Its activity also has been examined in several discriminative models of infection that mimic specific diseases in humans and permit testing of antimicrobial activity under a variety of defined pharmacokinetic conditions. These include experimental pneumonia in mice, a tissue cage model of foreign body infection in rats, and endocarditis models in rats and rabbits. In these models, ceftobiprole exhibits activity equivalent or superior to that of comparators against MRSA, including vancomycin-intermediate strains. These models also confirm the in-vivo activity of ceftobiprole against Gram-negative bacteria that are susceptible in vitro. The results from animal models support the evaluation of the clinical efficacy of ceftobiprole in humans and also predict clinical efficacy in the empirical treatment of severe infections. The broad spectrum of activity may allow ceftobiprole to be used as monotherapy for serious hospital-acquired infections where combination therapy would otherwise be required.