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

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.