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

J Antimicrob Chemother. 2017 May 1;72(5):1433-1440. doi: 10.1093/jac/dkw592.

Abstract

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.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / pharmacology
  • Ceftazidime / administration & dosage
  • Ceftazidime / blood
  • Ceftazidime / pharmacokinetics*
  • Ceftazidime / pharmacology
  • Computer Simulation*
  • Critical Illness
  • Female
  • Hospitals, University
  • Humans
  • Intensive Care Units
  • Kinetics
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Monte Carlo Method
  • Pseudomonas aeruginosa / drug effects
  • Renal Dialysis*
  • Sepsis / complications
  • Sepsis / drug therapy

Substances

  • Anti-Bacterial Agents
  • Ceftazidime