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

Konig, Christina, Braune, Stephan, Roberts, Jason A., Nierhaus, Axel, Steinmetz, Oliver M., Baehr, Michael, Frey, Otto R., Langebrake, Claudia and Kluge, Stefan (2017) Population pharmacokinetics and dosing simulations of ceftazidime in critically ill patients receiving sustained low-efficiency dialysis. Journal of Antimicrobial Chemotherapy, 72 5: 1433-1440. doi:10.1093/jac/dkw592


Author Konig, Christina
Braune, Stephan
Roberts, Jason A.
Nierhaus, Axel
Steinmetz, Oliver M.
Baehr, Michael
Frey, Otto R.
Langebrake, Claudia
Kluge, Stefan
Title Population pharmacokinetics and dosing simulations of ceftazidime in critically ill patients receiving sustained low-efficiency dialysis
Journal name Journal of Antimicrobial Chemotherapy   Check publisher's open access policy
ISSN 1460-2091
0305-7453
Publication date 2017-05-01
Year available 2017
Sub-type Article (original research)
DOI 10.1093/jac/dkw592
Open Access Status Not yet assessed
Volume 72
Issue 5
Start page 1433
End page 1440
Total pages 8
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Abstract Objectives: To describe the population PKs of ceftazidime in critically ill patients receiving sustained low-efficiency dialysis (SLED).
Formatted 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 PmetricsVR. 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 offSLED 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.
Keyword Extended Daily Dialysis
Acute-Renal-Failure
Acute Kidney Injury
Continuous Venovenous Hemofiltration
Care-Unit Patients
Septic Shock
Replacement Therapy
Severe Sepsis
Hemodialysis
Removal
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID APP1117065
APP1099452
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
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