Population pharmacokinetics and dosing simulations of ceftazidime in critically ill patients receiving sustained low-efficiency dialysis.
To describe the population PKs of ceftazidime in critically ill patients receiving sustained low-efficiency dialysis (SLED).



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 .



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%.



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.
Hospital Pharmacy, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.|Department of Intensive Care Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Christina
C
König
Department of Intensive Care Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Stephan
S
Braune
Burns, Trauma, and Critical Care Research Centre and Centre for Translational Anti-infective Pharmacodynamics, The University of Queensland, Brisbane, Australia.
Jason A
JA
Roberts
Department of Intensive Care Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Axel
A
Nierhaus
University Medical Center Hamburg-Eppendorf, Department of Internal Medicine III. (Nephrology/Rheumatology with Section Endocrinology), Hamburg, Germany.
Oliver M
OM
Steinmetz
Hospital Pharmacy, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Michael
M
Baehr
Hospital Pharmacy, General Hospital of Heidenheim, Heidenheim, Germany.
Otto R
OR
Frey
Hospital Pharmacy, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.|Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Claudia
C
Langebrake
Department of Intensive Care Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Stefan
S
Kluge
D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D002442:Ceftazidime / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D003198:Computer Simulation; D016638:Critical Illness; D005260:Female; D006785:Hospitals, University; D006801:Humans; D007362:Intensive Care Units; D007700:Kinetics; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009010:Monte Carlo Method; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D006435:Renal Dialysis; D018805:Sepsis / Q000150:complications / Q000188:drug therapy
D000900:Anti-Bacterial Agents; D002442:Ceftazidime