Pharmacodynamics of ceftaroline fosamil for complicated skin and skin structure infection: rationale for improved anti-methicillin-resistant Staphylococcus aureus activity.
J Antimicrob Chemother. 2010 Nov;65 Suppl 4:iv33-9
Authors: Drusano GL
Ceftaroline fosamil is a new ?-lactam antibiotic with an altered 3' side chain that allows it to interact with penicillin-binding protein (PBP) 2a, resulting in lower MIC values for methicillin-resistant Staphylococcus aureus (MRSA). Large MRSA collections repeatedly demonstrate MIC?? values of 1 mg/L. The pharmacokinetics for ceftaroline fosamil are straightforward and reminiscent of many other cephalosporin antibiotics, with a terminal half-life of ?2.6 h. Pharmacodynamic evaluation demonstrates that relatively short free drug T? > ?MIC results in stasis or 1 log?? cfu/g bacterial kill (mean values for four S. aureus isolates of 26% and 33% of the dosing interval, respectively). Monte Carlo simulation demonstrated high expected target attainment rates (> 97%) and clinical trial data showed clinically evaluable and microbiologically evaluable cure rates (96.7%) that are highly concordant with the pharmacodynamic analyses. Clinical trial data for ceftaroline fosamil are in excellent concordance with the pharmacodynamic analysis. Ceftaroline fosamil at a dose of 600 mg administered intravenously every 12 h is highly likely to be successful in clinical practice for treatment of complicated skin and skin structure infections.
PMID: 21115453 [PubMed - in process]