Population pharmacokinetics of ceftriaxone administered as continuous or intermittent infusion in critically ill patients. (4th March 2020)

• Record Type: Journal Article
• Authors: Leegwater, E; Kraaijenbrink, B V C; Moes, D J A R; Purmer, I M; Wilms, E B
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 75:Number 6(2020)
• Page Start: 1554
• Page End: 1558
• Publication Date: 2020-03-04
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkaa067
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract: Objectives: To describe the population pharmacokinetics and protein-binding characteristics of unbound ceftriaxone administered as continuous or intermittent infusion. Additionally, to determine the optimal dosing regimen in critically ill patients. Methods: A pharmacokinetic study was performed in the ICU of a tertiary teaching hospital. Patients were treated with ceftriaxone as continuous or intermittent infusion. A population pharmacokinetic model was developed with non-linear mixed-effects analysis. Subsequently, the PTA of a 100% T >MIC was assessed for influential patient characteristics using Monte Carlo simulation. Results: Fifty-five patients were included. The pharmacokinetics of ceftriaxone was best described by a one-compartment model with non-linear saturable protein binding including the following covariates: body weight, estimated CLCR, serum albumin concentration and mode of administration. For pathogens with an MIC of 1 mg/L, the simulation demonstrated that intermittent infusion of 2 g/24 h only resulted in a ≥90% PTA in patients with a reduced CLCR (0–60 mL/min). Intermittent infusion of 2 g/12 h led to sufficient exposure if CLCR was 0–90 mL/min and continuous infusion of 2 g/24 h led to a ≥90% PTA in all simulations (CLCR 0–180 mL/min). Conclusions: In the critically ill, the clearance of unbound ceftriaxone is closely related to CLCR . Furthermore, ceftriaxone protein binding is saturable, variable and dependent on serum albumin concentration. Intermittent dosing of 2 g/24 h ceftriaxone leads to subtherapeutic exposure in patients with a normal or increased CLCR . Treating these patients with continuous infusion of 2 g/24 h is more effective than an intermittent dosing regimen of 2 g/12 h.