Pharmacokinetic and Pharmacodynamic Target Attainment in Adult and Pediatric Patients Following Administration of Ceftaroline Fosamil as a 5‐Minute Infusion

The key pharmacokinetic/pharmacodynamic (PK/PD) efficacy index for β-lactam antibiotics is the percentage of time that free drug concentrations exceed the minimum inhibitory concentration (MIC) of bacteria during each dosing interval (fT>MIC). Ceftaroline fosamil, the prodrug of the β-lactam ceftaroline, was initially approved for administration as 60-minute intravenous (IV) infusions. Population PK analyses comparing exposure and PK/PD target attainment for 5-minute and 60-minute IV infusions, described here, have supported ceftaroline fosamil labeling updates to include variable infusion durations of 5 to 60 minutes in adults and children aged ≥2 months. A 2-compartment disposition PK model for ceftaroline fosamil and ceftaroline was used to predict steady-state ceftaroline exposures (maximum plasma concentrations [Cmax,ss ] and area under the plasma concentration-time curve over 24 hours [AUCss,0-24 ]) and probability of target attainment in simulated adult and pediatric patients with various degrees of renal function receiving standard doses of ceftaroline fosamil as 5-minute or 60-minute IV infusions. Across age groups and renal function categories, median ceftaroline AUCss,0-24 values were similar for 5-minute and 60-minute infusions, whereas Cmax,ss was up to 42% higher for 5-minute infusions. Both infusion durations achieved >99% probability of target attainment based on PK/PD targets for Staphylococcus aureus (35% fT>MIC) and Streptococcus pneumoniae (44% fT>MIC) at European Committee on Antimicrobial Susceptibility Testing/Clinical and Laboratory Standards Institute MIC breakpoints (1 mg/L and 0.25/0.5 mg/L, respectively). These findings support administration of standard ceftaroline fosamil doses over 5 to 60 minutes for adults and children aged ≥2 months, providing added flexibility to clinicians and patients.