Are Standard Dosing Regimens of Ceftriaxone Adapted for Critically Ill Patients with Augmented Creatinine Clearance?

Autor: Ollivier J; Pharmacy and Clinical Pharmacy Department, CHU Bordeaux, Bordeaux, France., Carrié C; Anesthesiology and Critical Care Department, CHU Bordeaux, Bordeaux, France cedric.carrie@chu-bordeaux.fr., d'Houdain N; Pharmacy and Clinical Pharmacy Department, CHU Bordeaux, Bordeaux, France., Djabarouti S; Pharmacy and Clinical Pharmacy Department, CHU Bordeaux, Bordeaux, France.; Pharmacokinetics and PK/PD Group, INSERM 1034, Université Bordeaux, Bordeaux, France., Petit L; Anesthesiology and Critical Care Department, CHU Bordeaux, Bordeaux, France., Xuereb F; Pharmacy and Clinical Pharmacy Department, CHU Bordeaux, Bordeaux, France.; Pharmacokinetics and PK/PD Group, INSERM 1034, Université Bordeaux, Bordeaux, France.; Université Bordeaux Segalen, Bordeaux, France., Legeron R; Pharmacy and Clinical Pharmacy Department, CHU Bordeaux, Bordeaux, France.; Pharmacokinetics and PK/PD Group, INSERM 1034, Université Bordeaux, Bordeaux, France.; Université Bordeaux Segalen, Bordeaux, France., Biais M; Anesthesiology and Critical Care Department, CHU Bordeaux, Bordeaux, France.; Université Bordeaux Segalen, Bordeaux, France., Breilh D; Pharmacy and Clinical Pharmacy Department, CHU Bordeaux, Bordeaux, France.; Pharmacokinetics and PK/PD Group, INSERM 1034, Université Bordeaux, Bordeaux, France.; Université Bordeaux Segalen, Bordeaux, France.
Jazyk: angličtina
Zdroj: Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2019 Feb 26; Vol. 63 (3). Date of Electronic Publication: 2019 Feb 26 (Print Publication: 2019).
DOI: 10.1128/AAC.02134-18
Abstrakt: The objective of the present study was to determine whether augmented renal clearance (ARC) impacts negatively on ceftriaxone pharmacokinetic (PK)/pharmacodynamic (PD) target attainment in critically ill patients. Over a 9-month period, all critically ill patients treated with ceftriaxone were eligible. During the first 3 days of antimicrobial therapy, every patient underwent 24-h creatinine clearance (CL CR ) measurements and therapeutic drug monitoring of unbound ceftriaxone. ARC was defined by a CL CR of ≥150 ml/min. Empirical underdosing was defined by a trough unbound ceftriaxone concentration under 2 mg/liter (percentage of the time that the concentration of the free fraction of drug remained greater than the MIC [ fT >MIC ], 100%). Monte Carlo simulation (MCS) was performed to determine the probability of target attainment (PTA) of different dosing regimens for various MICs and three groups of CL CR (<150, 150 to 200, and >200 ml/min). Twenty-one patients were included. The rate of empirical ceftriaxone underdosing was 62% (39/63). A CL CR of ≥150 ml/min was associated with empirical target underdosing with an odds ratio (OR) of 8.8 (95% confidence interval [CI] = 2.5 to 30.7; P  < 0.01). Ceftriaxone PK concentrations were best described by a two-compartment model. CL CR was associated with unbound ceftriaxone clearance ( P  = 0.02). In the MCS, the proportion of patients who would have failed to achieve a 100% fT >MIC was significantly higher in ARC patients for each dosage regimen (OR = 2.96; 95% CI = 2.74 to 3.19; P  < 0.01). A dose of 2 g twice a day was best suited to achieve a 100% fT >MIC When targeting a 100% fT >MIC for the less susceptible pathogens, patients with a CL CR of ≥150 ml/min remained at risk of empirical ceftriaxone underdosing. These data emphasize the need for therapeutic drug monitoring in ARC patients.
(Copyright © 2019 American Society for Microbiology.)
Databáze: MEDLINE
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