Related Experiment Video
Updated: Jun 11, 2026

Antimicrobial Synergy Testing by the Inkjet Printer-assisted Automated Checkerboard Array and the Manual Time-kill Method
Published on: April 18, 2019
Pharmacokinetic-pharmacodynamic modeling using combined time-kill data for meropenem and colistin or polymyxin B
Hiie Soeorg1, Sihong Lyu1, Frank Kloprogge2
1Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
Abstract:
Acinetobacter baumannii is a high-priority pathogen with increasing antimicrobial resistance levels, requiring combination treatment. We aimed to develop a pharmacokinetic-pharmacodynamic model of meropenem with colistin/polymyxin B against A. baumannii based on a systematic review of time-kill experiments to inform the effectiveness of this combination. PubMed was systematically searched for all studies describing time-kill experiments of meropenem and colistin/polymyxin B combinations against A. baumannii. Time-kill data and strain metadata were extracted. A pharmacokinetic-pharmacodynamic model with logistic growth, sigmoidal Emax killing functions of monotherapies, time-dependent attenuation of drug effect, and general pharmacodynamic interaction for the combination effect was fitted. Simulations were performed to produce dose recommendations. A total of 21 eligible papers were found reporting data from 369 experiments on 53 strains. Minimum inhibitory concentration (MIC) on EC50 (concentration achieving half-maximum killing), inoculum on Emax (maximum killing rate), and beta-lactamases on Emax for meropenem were covariates and both drugs. EC50 of both drugs included interisolate variability. The model showed that colistin/polymyxin B increased meropenem Emax and decreased its EC50. No interisolate variability in the interaction was supported by the model. Simulations showed that in pneumonia, undetectable growth at 24 h can be achieved with a probability of >90% only in strains with meropenem MIC ≤16 mg/L. The model suggests that colistin/polymyxin B enhances meropenem activity across a diverse set of strains but does not achieve adequate target attainment in resistant strains (colistin/polymyxin B MIC ≥1 mg/L and/or meropenem MIC >8 mg/L). The presence of acquired beta-lactamases reduces the effect of meropenem.
More Related Videos
09:17A Robust Pneumonia Model in Immunocompetent Rodents to Evaluate Antibacterial Efficacy against S. pneumoniae, H. influenzae, K. pneumoniae, P. aeruginosa or A. baumannii
Published on: January 2, 2017
07:16Development of a Polymicrobial Colony Biofilm Model to Test Antimicrobials in Cystic Fibrosis
Published on: September 20, 2024
Related Concept Videos
Pharmacodynamic Models: Overview
Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions
Combined Effects of Drugs: Synergism
Such synergistic combinations...
Pharmacokinetic–Pharmacodynamic Relationship: Influence of Elimination Half-Life on Effect Duration
Pharmacokinetic Models: Overview
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal assumptions,...
Pharmacokinetic–Pharmacodynamic Relationship: Problems