Pharmacodynamics of ceftaroline fosamil for complicated skin and skin structure infection: rationale for improved anti-methicillin-resistant Staphylococcus aureus activity.
Ceftaroline fosamil is a new β-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 MIC₉₀ 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 log₁₀ 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.
Ordway Research Institute, Albany, NY 12208, USA.
George L
GL
Drusano
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D002511:Cephalosporins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006207:Half-Life; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D046915:Penicillin-Binding Proteins / Q000378:metabolism; D017192:Skin Diseases, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D018461:Soft Tissue Infections / Q000188:drug therapy* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D000097583:Ceftaroline
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D046915:Penicillin-Binding Proteins; D000097583:Ceftaroline