Are Standard Dosing Regimens of Ceftriaxone Adapted for Critically Ill Patients with Augmented Creatinine Clearance? - Biology of Cardiovascular Diseases Accéder directement au contenu
Article Dans Une Revue Antimicrobial Agents and Chemotherapy Année : 2019

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

Résumé

ABSTRACT 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 \textgreaterMIC ], 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 (\textless150, 150 to 200, and \textgreater200 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 \textless 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 \textgreaterMIC was significantly higher in ARC patients for each dosage regimen (OR = 2.96; 95% CI = 2.74 to 3.19; P \textless 0.01). A dose of 2 g twice a day was best suited to achieve a 100% fT \textgreaterMIC . When targeting a 100% fT \textgreaterMIC 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.

Mots clés

Dates et versions

hal-03007510 , version 1 (16-11-2020)

Identifiants

Citer

Julien Ollivier, Cédric Carrié, Nicolas D’houdain, Sarah Djabarouti, Laurent Petit, et al.. Are Standard Dosing Regimens of Ceftriaxone Adapted for Critically Ill Patients with Augmented Creatinine Clearance?. Antimicrobial Agents and Chemotherapy, inPress, 63 (3), pp.e02134-18. ⟨10.1128/AAC.02134-18⟩. ⟨hal-03007510⟩

Collections

CNRS U1034
22 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More