Ceftaroline fosamil pharmacokinetics during cardiac surgery with cardiopulmonary bypass

Surgical site infections remain significant complications after cardiac surgery and perioperative antibiotic exposure may be altered by cardiopulmonary bypass and patient characteristics. Ceftaroline fosamil is active against methicillin resistant Staphylococcus aureus (MRSA) and may be a potential alternative for patients with risk factors for MRSA. However, parasternal subcutaneous tissue exposure during cardiac surgery has not been studied. This prospective, randomized pharmacokinetic study investigated plasma and parasternal subcutaneous concentrations in patients undergoing cardiac surgery with cardiopulmonary bypass. Fourteen patients were randomized to receive a total dose of 1,800 mg of ceftaroline fosamil administered either intermittently or by continuous infusion following a loading dose. Plasma and subcutaneous tissue concentrations were measured for 24 h using arterial blood sampling and in vivo microdialysis. Pharmacokinetic parameters and pharmacodynamic target attainment were assessed for both dosing regimens. In plasma, free drug concentrations remained above the MIC of 1 mg/L for nearly the entire dosing interval in both groups (mean fT>MIC ∼99–100%). Subcutaneous parasternal tissue concentrations were lower in both groups and showed marked interindividual variability. At an MIC of 1 mg/L, mean tissue fT>MIC ranged from 93% to 99% with intermittent and 75%–86% during continuous administration. These findings demonstrate that ceftaroline penetration into subcutaneous parasternal tissue is highly variable in cardiac surgery patients and may limit tissue exposure under perioperative conditions despite favorable plasma concentrations. While continuous infusion improves plasma exposure, this does not necessarily translate into superior tissue exposure. Therefore, measurement of tissue concentrations is important when evaluating antibiotic dosing strategies in the perioperative setting.