Duke, Carleigh

Parker, Suzanne L

Zam, Betty B

Chiong, Fabian

Sajiv, Cherian

Pawar, Basant

Ashok, Aadith

Cooper, Brynley

Tong, Steven Y C

Janson, Sonja

Wallis, Steven C

Roberts, Jason A

Tsai, Danny

2024-11-04

To describe the population pharmacokinetics of cefazolin in infected hospitalized patients requiring intermittent haemodialysis (IHD).This prospective population pharmacokinetic study was conducted in IHD patients prescribed cefazolin 2 g three times weekly. Plasma samples were collected at prespecified timepoints and assayed for total and unbound concentrations using validated LC. Pharmacokinetic modelling and dosing simulations were performed using Pmetrics®. PTA in plasma suitable for MSSA (unbound trough concentrations of ≥2 mg/L for the final 24 h of a 72 h interval) were simulated for different dosing regimens. A PTA of ≥95% was deemed acceptable.A total of 260 cefazolin concentrations (130 total, 130 unbound) were collected from 16 patients (14 female) with a median age of 51 years. The median (IQR) pre-dialysis unbound cefazolin concentration for a 3 day dose interval trough was 17.7 (13.5-31.4) mg/L. The median (IQR) unbound fraction was 0.38 (0.32-0.46). The lowest pre-dialysis unbound concentration was 9.1 mg/L. A two-compartment model with a complex protein-binding component adequately described the data. The mean unbound cefazolin CL during IHD was 16.4 ± 4.26 L/h, compared with 0.40 ± 0.19 L/h when dialysis was off. Duration of time on haemodialysis (TOH) was the only covariate supported in the final model. The 2 g three-times-weekly regimen was associated with a PTA of 99.7% on dosing simulations to maintain unbound concentrations of ≥2 mg/L with TOH of 6 months. The 1 g three-times-weekly post-dialysis was associated with a PTA of 95.4%.A 2 g three-times-weekly post-dialysis cefazolin regimen is supported for MSSA infections.

College of Medicine and Public Health, Flinders University, Corner Skinner and Simpson Streets, Darwin 0870, Northern Territory, Australia.

University of Queensland Centre for Clinical Research, University of Queensland, Brisbane, Queensland, Australia.

Pharmacy Department, Alice Springs Hospital, Alice Springs, Northern Territory, Australia.

Department of Medicine, Alice Springs Hospital, Alice Springs, Northern Territory, Australia.

Department of Nephrology, Alice Springs Hospital, Alice Springs, Northern Territory, Australia.

Victorian Infectious Diseases Service, The Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.

Department of Medicine, Alice Springs Hospital, Alice Springs, Northern Territory, Australia.

Pharmacy Department, Alice Springs Hospital, Alice Springs, Northern Territory, Australia.

Department of Nephrology, Alice Springs Hospital, Alice Springs, Northern Territory, Australia.

Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.

Department of Infectious Diseases, Royal Darwin Hospital, Darwin, Northern Territory, Australia.

University of Queensland Centre for Clinical Research, University of Queensland, Brisbane, Queensland, Australia.

University of Queensland Centre for Clinical Research, University of Queensland, Brisbane, Queensland, Australia.

Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.

Herston Infectious Diseases Institute (HeIDI), Metro North Health, Brisbane, QLD, Australia.

Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France.

College of Medicine and Public Health, Flinders University, Corner Skinner and Simpson Streets, Darwin 0870, Northern Territory, Australia.

University of Queensland Centre for Clinical Research, University of Queensland, Brisbane, Queensland, Australia.

Pharmacy Department, Alice Springs Hospital, Alice Springs, Northern Territory, Australia.

J Antimicrob Chemother . 2024 Nov 4;79(11):2980-2989. doi: 10.1093/jac/dkae318.

1460-2091

0009-0002-3093-7403

0000-0002-6124-7475

0000-0002-1368-8356

0000-0002-2392-9854

0000-0001-6218-435X

0000-0002-7059-8808

https://pubmed.ncbi.nlm.nih.gov/39255245/?otool=iaurydwlib

https://hdl.handle.net/10137/13786

Humans

Cefazolin

Middle Aged

Female

Male

Renal Dialysis

Anti-Bacterial Agents

Prospective Studies

Aged

Adult

Hospitalization

Bacterial Infections

Drug Administration Schedule

Population pharmacokinetics of unbound cefazolin in infected hospitalized patients requiring intermittent high-flux haemodialysis: can a three-times-weekly post-dialysis dosing regimen provide optimal treatment?

Journal Article

Publication