Related Experiment Video
Updated: Apr 21, 2026
Animal Model of Implant-Associated Infections in Mice
Published on: June 27, 2025
An optimized mouse thigh infection model for enterococci and its impact on antimicrobial pharmacodynamics
Carlos A Rodriguez1, Maria Agudelo2, Javier M Gonzalez2
1GRIPE (Grupo Investigador de Problemas en Enfermedades Infecciosas), Department of Pharmacology and Toxicology, School of Medicine, Universidad de Antioquia, Medellín, Colombia.
Abstract:
Negligible in vivo growth of enterococci and high-level dispersion of data have led to inaccurate estimations of antibiotic pharmacodynamics (PD). Here we improved an in vivo model apt for PD studies by optimizing the in vitro culture conditions for enterococci. The PD of vancomycin (VAN), ampicillin-sulbactam (SAM), and piperacillin-tazobactam (TZP) against enterococci were determined in vivo, comparing the following different conditions of inoculum preparation: aerobiosis, aerobiosis plus mucin, and anaerobiosis plus mucin. Drug exposure was expressed as the ratio of the area under the concentration-time curve for the free, unbound fraction of the drug to the MIC (fAUC/MIC) (VAN) or the time in a 24-h period that the drug concentration for the free, unbound fraction exceeded the MIC under steady-state pharmacokinetic conditions (fT(>MIC)) (SAM and TZP) and linked to the change in log10 CFU/thigh. Only anaerobiosis plus mucin enhanced the in vivo growth, yielding significant PD parameters with all antibiotics. In conclusion, robust in vivo growth of enterococci was crucial for better determining the PD of tested antibacterial agents, and this was achieved by optimizing the procedure for preparing the inoculum.
Insights
Optimizing in vitro culture conditions for enterococci significantly improved in vivo growth, enabling accurate antibiotic pharmacodynamics (PD) assessments. This enhanced model is crucial for understanding drug efficacy against enterococcal infections.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Inaccurate antibiotic pharmacodynamics (PD) estimations for enterococci stem from poor in vivo growth.
- Developing a reliable in vivo model is essential for accurate PD studies.
Purpose of the Study:
- To optimize in vitro culture conditions for enterococci to improve in vivo growth.
- To determine the in vivo pharmacodynamics of vancomycin, ampicillin-sulbactam, and piperacillin-tazobactam against enterococci.
Main Methods:
- Compared inoculum preparation methods: aerobiosis, aerobiosis plus mucin, and anaerobiosis plus mucin.
- Determined drug exposure using fAUC/MIC for vancomycin and fT(>MIC) for ampicillin-sulbactam and piperacillin-tazobactam.
- Linked drug exposure to changes in log10 CFU/thigh.
Main Results:
- Only anaerobiosis plus mucin significantly enhanced in vivo enterococcal growth.
- This optimized condition yielded significant PD parameters for all tested antibiotics.
- Robust in vivo growth is critical for accurate PD parameter determination.
Conclusions:
- Optimizing inoculum preparation is crucial for establishing robust enterococcal in vivo growth.
- This improved in vivo model facilitates accurate determination of antibiotic PD against enterococci.
- The findings support better therapeutic strategies for enterococcal infections.
