Meropenem dosing optimization on day 1 and steady state in critically ill patients without significant renal impairment

This study aimed to characterize meropenem pharmacokinetics and optimise dosing for the initial and steady state in critically ill patients. Adult patients receiving meropenem were recruited, with sampling performed on days 1 (Occasion 1) and 3 (Occasion 2) of therapy. A composite target of free drug concentrations above the minimum inhibitory concentration for the entire dosing interval (100%ƒT > MIC) and a concentration below the toxicity threshold of 45 mg/L was used. Thirty-seven patients, with a median age of 52 years, and a median estimated creatinine clearance (CLcr) and CKD Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (eGFR) of 68.6 mL/min and 78.2 mL/min/1.73 m², respectively, were recruited. Twenty-four patients reached the composite target on Occasion 1, and 21 on Occasion 2. No significant factors influenced target attainment on Occasion 1, but plasma albumin, CLcr, recent surgery, and infusion methods significantly influenced it on Occasion 2. A two-compartment model with first-order elimination best characterized meropenem's plasma pharmacokinetics, with CKD-EPI eGFR and recent surgery significantly affecting clearance. Continuous infusion achieved the highest probability of target attainment in dosing simulations for isolates with MIC of 2-8 mg/L. Our study demonstrates that renal function, recent surgical interventions, and infusion methods should be considered in optimizing meropenem dosing in critically ill patients.