Integration of individual preclinical and clinical anti‐infective PKPD data to predict clinical study outcomes DOI Creative Commons
Vincent Aranzana‐Climent, Wisse van Os, Amir Nutman

et al.

Clinical and Translational Science, Journal Year: 2024, Volume and Issue: 17(7)

Published: July 1, 2024

The AIDA randomized clinical trial found no significant difference in failure or survival between colistin monotherapy and colistin-meropenem combination therapy carbapenem-resistant Gram-negative infections. aim of this reverse translational study was to integrate all individual preclinical pharmacokinetic-pharmacodynamic (PKPD) data from the a pharmacometric framework explore whether individualized predictions bacterial burden were associated with outcomes. compiled dataset included for each 207 patients (i) information on infecting Acinetobacter baumannii isolate (minimum inhibitory concentration, checkerboard assay data, fitness murine model), (ii) plasma concentrations meropenem dosing history, (iii) disease scores demographics. integrated into PKPD models, predicted change count at 24 h patient, as well patient characteristics, correlated outcomes using logistic regression. vivo most important factor count. A model-predicted growth ≥2-log

Language: Английский

Population Pharmacokinetics of Prolonged Infusion for Meropenem: Tailoring Dosing Recommendations for Chinese Critically Ill Patients on Continuous Renal Replacement Therapy with Consideration for Renal Function DOI Creative Commons

Yaru Peng,

Yanan Liu,

Zeneng Cheng

et al.

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 1105 - 1117

Published: Feb. 1, 2025

Extended meropenem infusion is increasingly employed to enhance clinical outcomes in critically ill patients. Nonetheless, investigations into such dosing regimens renal-impaired patients undergoing continuous renal replacement therapy (CRRT) are scarce. This study aims perform a population pharmacokinetic (PK) analysis of prolonged CRRT inform optimal regimens. Ninety-four concentrations from 21 Chinese receiving 1 g every 8-12 hours infused over 2-3 were utilized construct the PK model. Monte Carlo simulations assess efficacy based on PK/PD targets (100% fT>MIC or 100% fT>4×MIC) and risk nephrotoxicity (trough concentration ≥45 mg/L) for extended (0.5-2 with 3-hour administered 6-12 hours). Meropenem data was adequately described by one-compartment model linear elimination, creatinine clearance (CLCR) significantly influenced meropenem's endogenous clearance. 0.5 q6h q8h could achieve desirable attainment target against an MIC≤4 mg/L, negligible toxicity across CLCR range 10-50 mL/min. 2 required targeting fT>4×MIC patients, but associated very high (>20%). A developed may be regimen infusion.

Language: Английский

Citations

0
Sampling from covariate distribution may not always be necessary in PK/PD simulations: illustrative examples with antibiotics DOI
Feiyan Liu,

Zeneng Cheng,

Sanwang Li

et al.

Journal of Pharmacokinetics and Pharmacodynamics, Journal Year: 2025, Volume and Issue: 52(2)

Published: March 4, 2025

Language: Английский

Citations

0
Multistate modeling for survival analysis in critically ill patients treated with meropenem DOI Creative Commons

Yaru Peng,

Iris K. Minichmayr, Han Liu

et al.

CPT Pharmacometrics & Systems Pharmacology, Journal Year: 2023, Volume and Issue: 13(2), P. 222 - 233

Published: Oct. 26, 2023

Abstract Appropriate antibiotic dosing to ensure early and sufficient target attainment is crucial for improving clinical outcome in critically ill patients. Parametric survival analysis a preferred modeling method quantify time‐varying exposure – response effects, whereas bias may be introduced hazard functions when competing events occur. This study investigated predictors of in‐hospital mortality patients treated with meropenem by pharmacometric multistate modeling. A model comprising five states (ongoing treatment, other treatment termination, discharge, death) was developed capture the transitions cohort 577 meropenem. Various factors were as potential transitions, including patient demographics, creatinine clearance calculated Cockcroft–Gault equation (CLCR CG ), time that unbound concentrations exceed minimum inhibitory concentration ( f T >MIC microbiology‐related measures. The probabilities transit from ongoing increased over time. 10 mL/min decrease CLCR found elevate transitioning termination death state 18%. 100% significantly transition rate (by 9.7%), associated improved outcome. prospectively assessed can serve useful tool different infection scenarios, particularly risks are present.

Language: Английский

Citations

4
Integration of individual preclinical and clinical anti‐infective PKPD data to predict clinical study outcomes DOI Creative Commons
Vincent Aranzana‐Climent, Wisse van Os, Amir Nutman

et al.

Clinical and Translational Science, Journal Year: 2024, Volume and Issue: 17(7)

Published: July 1, 2024

The AIDA randomized clinical trial found no significant difference in failure or survival between colistin monotherapy and colistin-meropenem combination therapy carbapenem-resistant Gram-negative infections. aim of this reverse translational study was to integrate all individual preclinical pharmacokinetic-pharmacodynamic (PKPD) data from the a pharmacometric framework explore whether individualized predictions bacterial burden were associated with outcomes. compiled dataset included for each 207 patients (i) information on infecting Acinetobacter baumannii isolate (minimum inhibitory concentration, checkerboard assay data, fitness murine model), (ii) plasma concentrations meropenem dosing history, (iii) disease scores demographics. integrated into PKPD models, predicted change count at 24 h patient, as well patient characteristics, correlated outcomes using logistic regression. vivo most important factor count. A model-predicted growth ≥2-log

Language: Английский

Citations

1