Simulated endocardial vegetation model highlights the complexity of high-inoculum infections among β-lactamase-producing organisms

TL;DR

This study shows that standard antibiotic testing methods may not accurately predict treatment outcomes for high-inoculum infections caused by bacteria that produce β-lactamase.

Contribution

The study introduces a simulated endocardial vegetation model to better understand antibiotic efficacy and resistance in high-inoculum infections.

Findings

MIC values were often not predictive of antibiotic efficacy in high-inoculum scenarios.

Resistance emergence and β-lactamase expression varied with antibiotic exposure in the model.

Standard inoculum testing may underestimate challenges in treating β-lactamase-producing infections.

Abstract

Conventionally, susceptibility testing and pharmacokinetic/pharmacodynamic relationships are determined using standard inoculum (i.e., 105–106 CFU). These may be poorly predictive of efficacy for high-inoculum infections, especially amongst β-lactamase-producing organisms. A. J. Kunz-Coyne, R. Gray, E. May, H. Curry, et al. (Antimicrob Agents Chemother 69:e01170-25, 2025, https://doi.org/10.1128/aac.01170-25) used a 96-h simulated endocardial vegetation model to describe pharmacodynamic efficacy, resistance emergence, and β-lactamase expression that resulted after clinically relevant exposures of antibiotics against three Enterobacter cloacae complex isolates, demonstrating that MIC values were often poorly predictive of efficacy in the model.