Evaluation of Empirical Dosing Regimens for Meropenem in Intensive Care Unit Patients Using Population Pharmacokinetic Modeling and Target Attainment Analysis
01/2023
Journal Article
Authors:
An, G.;
Creech, C. B.;
Wu, N.;
Nation, R. L.;
Gu, K.;
Nalbant, D.;
Jimenez-Truque, N.;
Fissell, W.;
Rolsma, S.;
Patel, P. C.;
Watanabe, A.;
Fishbane, N.;
Kirkpatrick, C. M. J.;
Landersdorfer, C. B.;
Winokur, P.
Volume:
67
Pagination:
e0131222
Issue:
1
Journal:
Antimicrob Agents Chemother
PMID:
36622154
URL:
https://www.ncbi.nlm.nih.gov/pubmed/36622154
Keywords:
Humans Meropenem/pharmacokinetics *Anti-Bacterial Agents/pharmacokinetics Prospective Studies Creatinine Bayes Theorem *Intensive Care Units Critical Illness/therapy
Monte Carlo Method Microbial Sensitivity Tests ICU patients meropenem dose regimen population pharmacokinetics target attainment analysis
Abstract:
In the present study, population pharmacokinetic (PK) analysis was performed based on meropenem data from a prospective study conducted in 114 critically ill patients with a wide range of renal functions and various disease conditions. The final model was a one-compartment model with linear elimination, with creatinine clearance and continuous renal replacement therapy affecting clearance, and total bodyweight impacting the volume of distribution. Our model is a valuable addition to the existing meropenem population PK models, and it could be particularly useful during implementation of a therapeutic drug monitoring program combined with Bayesian forecasting. Based on the final model developed, comprehensive Monte Carlo simulations were performed to evaluate the probability of target attainment (PTA) of 16 different dosing regimens. Simulation results showed that 2 g administered every 8 h with 3-h prolonged infusion (PI) and 4 g/day by continuous infusion (CI) appear to be two empirical dosing regimens that are superior to many other regimens when both target attainment and potential toxicity are considered and renal function information is not available. Following a daily CI dose of 6 g or higher, more than 30% of the population with a creatinine clearance of <60 mL/min is predicted to have neurotoxicity. With the availability of institution- and/or unit-specific meropenem susceptibility patterns, as well as an individual patient's renal function, our PTA results may represent useful references for physicians to make dosing decisions.
