Ceftaroline: a comprehensive update.

Ceftaroline is a novel broad-spectrum cephalosporin antibiotic currently under US Food and Drug Administration (FDA) review for a new drug application (NDA), filed by Cerexa, Inc. (a wholly owned subsidiary of Forest Laboratories), for the treatment of complicated skin and skin-structure infections (cSSSIs) and community-associated pneumonia (CAP). The antibiotic acts by binding to penicillin-binding proteins in bacteria, consistent with other β-lactams. The antimicrobial spectrum of ceftaroline ranges from aerobic and anaerobic Gram-positive bacteria, including drug-resistant isolates of staphylococci, i.e. heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA), vancomycin-intermediate S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA), to anaerobic Gram-negative pathogens such as Moraxella catarrhalis and Haemophilus influenzae (including β-lactamase-positive strains), as well as bacteria with multiple resistance phenotypes. Ceftaroline fosamil is the prodrug that is rapidly dephosphorylated by in vivo plasma phosphatases to the active drug ceftaroline, which follows a two-compartmental pharmacokinetic model and is eliminated primarily by renal excretion, with a plasma half-life of ca. 2.5 h. Ceftaroline is well tolerated, which is consistent with its good safety profile similar to other cephalosporins in clinical trials. Thus, it would be a promising drug to fight multidrug-resistant superbugs such as S. aureus and Streptococcus pneumoniae for the treatment of cSSSIs and CAP.