Ceftobiprole/Ceftobiprole medocaril

Abstract

Over the past decade, resistance to antimicrobials has increased dramatically and is limiting the therapeutic options for the treatment and management of serious bacterial infections. Cephalosporins are commonly used to treat bacterial infections due to their broad spectrum of activity and low toxicity. However, the incidence of cephalosporin-resistant strains is increasing, thus decreasing the routine use of these agents. Researchers have focused on developing novel (3-lactam antibiotics which are active against resistant bacteria. One particular novel agent is ceftobiprole, which is the first of a new class of parenteral cephem antibiotics. This fourth-generation cephalosporin was designed to have strong affinity for penicillin-binding proteins conferring resistance in staphylococci, pneumococci and other Gram-positive and Gram-negative pathogens, and was shown to have broad-spectrum efficacy and a low propensity to induce resistance in vitro. Ceftobiprole is administered in vivo as the water-soluble prodrug ceftobiprole medocaril, which is rapidly cleaved in plasma to form ceftobiprole. Ceftobiprole medocaril exhibited potent efficacy in animal infection models and proved safe and effective in a phase II trial in patients with complicated skin and skin structure infections. Ceftobiprole medocaril has advanced to phase III development for the treatment of bacterial infections, particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA).