Population pharmacokinetics and dosing simulations of ceftazidime in critically ill patients receiving sustained low-efficiency dialysis

Objectives: To describe the population PKs of ceftazidime in critically ill patients receiving sustained low-efficiency dialysis (SLED). Patients and methods: This study was performed in ICUs of a university hospital. We collected blood samples during three consecutive days of SLED sessions in patients receiving ceftazidime. Concentration versus time curves were analysed using a population PKs approach with Pmetrics®. Monte Carlo simulation for the first 24 h including a 6 h SLED session was performed with the final model. The fractional target attainment against the MIC of Pseudomonas aeruginosa was executed using targets of 50 and 100% fT > MIC. Results: In total, 211 blood samples of 16 critically ill patients under SLED were collected. SLED treatments were 299.3 (68.4) min in duration. A two-compartment linear population PK model was most appropriate. The mean (SD) CL of ceftazidime on SLED, and off SLED were 5.32 (3.2), 1.06 (1.0) L/h respectively. The PTA for 50% fT > MIC for a dose of 1 g intravenously every 8 h was 98%. Assuming a target of 100% fT > MIC a dose of 2 g every 12 h covers isolates with MIC ≤8 mg/L with a PTA of 96%. Conclusion: In critically ill patients receiving SLED, ceftazidime 1 g every 8 h and ceftazidime 2 g every 12 h appear to be sufficient for achieving traditional (50% fT > MIC) and aggressive PD targets (100% fT > MIC) for susceptible isolates (MIC ≤8 mg/L), respectively.