Abstract
The aim of this study was to investigate optimal loading doses prior to continuous infusion of meropenem in critically ill patients. A previously published and successfully evaluated pharmacokinetic model of critically ill patients was used for stochastic simulations of virtual patients. Maintenance doses administered as continuous infusion of 1.5–6 g/24 h with preceding loading doses (administered as 30 min infusion) of 0.15–2 g were investigated. In addition to the examination of the influence of individual covariates, a best-case and worst-case scenario were simulated. Dosing regimens were considered adequate if the 5th percentile of the concentration–time profile did not drop at any time below four times the S/I breakpoint (= 2 mg/L) of Pseudomonas aeruginosa according to the EUCAST definition. Low albumin concentrations, high body weight and high creatinine clearances increased the required loading dose. A maximum loading dose of 0.33 g resulted in sufficient plasma concentrations when only one covariate showed extreme values. If all three covariates showed extreme values (= worst-case scenario), a loading dose of 0.5 g was necessary. Higher loading doses did not lead to further improvements of target attainment. We recommend the administration of a loading dose of 0.5 g meropenem over 30 min immediately followed by continuous infusion.
Highlights
The aim of this study was to investigate optimal loading doses prior to continuous infusion of meropenem in critically ill patients
Abbreviations S/I Susceptible/susceptible with increased exposure EUCAST European Committee on Antimicrobial Susceptibility Testing PK/PD Pharmacokinetic/Pharmacodynamic fT > MIC Time of the free drug above the minimal inhibitory concentration CLCR Clearance creatinine according to Cockcroft and Gault LD Loading dose
This study aimed to identify the optimal loading dose when meropenem is subsequently administered as continuous infusion in critically ill patients
Summary
The aim of this study was to investigate optimal loading doses prior to continuous infusion of meropenem in critically ill patients. Administering meropenem as a continuous infusion and starting with the maintenance rate would lead to a period below the MIC in the increasing part of the concentration-time profile. This should be avoided especially at the beginning of a course of treatment, when adequate antibiotic exposure is k ey[2,5]. This study aimed to identify the optimal loading dose when meropenem is subsequently administered as continuous infusion in critically ill patients. For this purpose, a simulation study was conducted based on data of a prospective PK study
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