Cefepime population pharmacokinetics and target attainment in critically ill patients on continuous renal replacement therapy.

Sepsis causes half of acute kidney injuries in the intensive care unit (ICU). ICU patients may need continuous renal replacement therapy (CRRT) which will affect their antimicrobial exposure. We aim to build a cefepime population pharmacokinetic (PK) model in CRRT ICU patients and perform simulations to assess target attainment. Patients who were ≥18 years old, admitted to the ICU, and received cefepime 2 g every 8 hours as 4-hour infusion while on CRRT were enrolled prospectively. Samples were collected from the predialyzer, postdialyzer ports, and effluent fluid at times 1, 2, 3, 4, and 8 hours after the first dose and at steady state. Age, sex, weight, urine output, and CRRT parameters were recorded. Pmetrics was used for population PK and simulations. The target exposure was 100% fT>MIC Ten patients were included and their mean age was 53 years and weight 119 kg. Seventy percent were males. Cefepime was described by a five-compartment model. The downtime was applied to the CRRT flow rates which were used to describe the rates of transfer between the compartments. At MIC of ≤8 mg/L, cefepime 2g intermittent infusion every 8 hours achieved good target attainment both early in therapy and at steady state. Only extended and continuous infusion regimens achieved good target attainment at MIC 16 mg/L. In conclusion, cefepime 2g infused over 30 minutes followed by 2g extended infusion every 8 hours achieved good target attainment at MIC ≤16 mg/L with different CRRT flow rates and may be considered in resistant bacterial infections.