Ceftobiprole, an investigational
beta-lactam antibiotic, has been shown to have a broad spectrum of activity against Gram-positive and Gram-negative pathogens. Unlike currently available
beta-lactams,
ceftobiprole has been shown to be active against methicillin-resistant staphylococci because of its high affinity for
penicillin-binding protein (PBP) 2' (2a).
Ceftobiprole has undergone extensive evaluation in phase I studies to characterise dose, pharmacokinetics, and safety/tolerability. In an early phase II study, all 35 clinically evaluable patients (n = 40) with complicated skin and skin structure
infections (cSSSIs) receiving intravenous
ceftobiprole 750 mg twice-daily were cured, including four of four patients with methicillin-resistant Staphylococcus aureus (MRSA). Microbiological eradication was achieved in 91% (21/23) of evaluable patients. On the basis of these results, phase III studies of
ceftobiprole for the treatment of cSSSIs were initiated. One study compared intravenous
ceftobiprole (500 mg every 12 h) to intravenous
vancomycin (1 g every 12 h) in patients with cSSSIs due to Gram-positive bacteria. Staphylococci were the predominant pathogens, and more than 25% of the microbiologically evaluable patients had
infections caused by MRSA. In the clinically evaluable population, efficacy and adverse events were comparable between treatment arms. Additional clinical trials in cSSSI and
pneumonia patients are underway to evaluate
ceftobiprole for the treatment of
infections due to both Gram-positive and Gram-negative bacteria.
Ceftobiprole is the first
cephalosporin to demonstrate clinical efficacy in patients with
infections due to methicillin-resistant staphylococci and, if approved by regulatory authorities, is expected to be a useful addition to the armamentarium of agents for the treatment of complicated skin
infections and
pneumonia.