Ceftaroline: a new cephalosporin with activity against resistant gram-positive pathogens

Molly E Steed, Michael J Rybak
Pharmacotherapy 2010, 30 (4): 375-89
Ceftaroline is a novel, broad-spectrum, advanced-generation cephalosporin whose action is mediated by binding to penicillin-binding proteins in bacteria, consistent with other beta-lactam antibiotics. Ceftaroline is distinct in that it has antimicrobial activity against multidrug-resistant Staphylococcus aureus (including methicillin-resistant S. aureus, vancomycin-intermediate S. aureus [VISA], heteroresistant VISA, and vancomycin-resistant S. aureus), Streptococcus pneumonia (including drug-resistant strains), and respiratory gram-negative pathogens such as Moraxella catarrhalis and Haemophilus influenzae (including beta-lactamase-positive strains). Development of resistance to ceftaroline occurs rarely in gram-positive bacteria and at a similar rate to that of other oxyimino-cephalosporins in gram-negative bacteria. The inactive prodrug, ceftaroline fosamil, is administered by intravenous infusion and rapidly undergoes biotransformation to ceftaroline. Ceftaroline then follows a two-compartment pharmacokinetic model and is eliminated primarily by renal excretion, with a half-life of approximately 3 hours. Similar to other cephalosporins, time above the minimum inhibitory concentration is the pharmacodynamic parameter that best predicts efficacy for ceftaroline. Ceftaroline 600 mg intravenously every 12 hours has been shown to have similar efficacy to vancomycin plus aztreonam for the treatment of complicated skin and skin structure infections and to ceftriaxone for the treatment of community-acquired bacterial pneumonia in phase III clinical trials. Ceftaroline displayed a safety profile similar to that of other cephalosporins in clinical trials. Dosage adjustment is required for moderate renal impairment and for patients receiving hemodialysis. Ceftaroline breakpoints have been proposed but not confirmed. Ceftaroline is a renally excreted broad-spectrum cephalosporin that is clinically effective for the treatment of complicated skin and skin structure infections and community-acquired bacterial pneumonia, and it has distinctive activity against some difficult-to-treat multidrug-resistant gram-positive organisms.

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