Simulated endocardial vegetation model highlights the complexity of high-inoculum infections among...

Area of Science:

• Microbiology
• Pharmacology
• Infectious Diseases

Background:

• Standard inoculum concentrations (10^5–10^6 CFU) in susceptibility testing may not reflect high-inoculum infections.
• This limitation is particularly relevant for beta-lactamase-producing organisms, potentially impacting treatment efficacy predictions.

Purpose of the Study:

• To evaluate antibiotic pharmacodynamic efficacy, resistance emergence, and beta-lactamase expression.
• To assess the predictive value of standard minimum inhibitory concentration (MIC) breakpoints in a simulated high-inoculum infection model.

Main Methods:

• Utilized a 96-hour simulated endocardial vegetation model.
• Exposed three *Enterobacter cloacae* complex isolates to clinically relevant antibiotic exposures.
• Monitored pharmacodynamic efficacy, resistance development, and beta-lactamase activity.

Main Results:

• Minimum inhibitory concentration (MIC) values were frequently poor predictors of antibiotic efficacy in the simulated high-inoculum model.
• Observed resistance emergence and beta-lactamase expression under clinically relevant antibiotic exposures.
• Demonstrated limitations of standard MIC testing for high-inoculum *Enterobacter cloacae* infections.

Conclusions:

• Standard susceptibility testing using conventional inoculum may not accurately predict outcomes for high-inoculum infections caused by beta-lactamase-producing bacteria.
• A simulated endocardial vegetation model provides a more relevant platform for assessing antibiotic efficacy and resistance dynamics in complex infections.