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Human-Simulated Antimicrobial Regimens in Animal Models: Transparency and Validation Are Imperative
Christian M Gill1, Tomefa E Asempa1, David P Nicolau2,3
1Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA.
Antimicrobial Agents and Chemotherapy
|May 20, 2020
Summary
Human-simulated regimens (HSRs) in animal models optimize antimicrobial dosing. This study compares two meropenem-vaborbactam HSR profiles in mice to assess their impact on bacterial killing and clinical relevance.
Area of Science:
- Pharmacology
- Infectious Diseases
- Microbiology
Background:
- Animal infection models are crucial for optimizing human antimicrobial dosage.
- Human-simulated regimens (HSRs) allow antimicrobial efficacy evaluation at clinically relevant concentrations.
- Pharmacokinetic studies in infected animals are essential for assessing drug concentrations.
Purpose of the Study:
- To present and compare two murine meropenem-vaborbactam HSR profiles.
- To evaluate the potential impact of these HSRs on bacterial killing.
- To assess the clinical translatability of meropenem-vaborbactam HSRs in a murine model.
Main Methods:
- Establishing and characterizing two distinct meropenem-vaborbactam HSR profiles in infected mice.
- Conducting pharmacokinetic analyses to confirm HSR profiles.
- Evaluating bacterial killing and drug concentration relationships.
Main Results:
- Comparison of two meropenem-vaborbactam HSR profiles in a murine infection model.
- Assessment of the impact of different HSRs on antimicrobial efficacy.
- Analysis of pharmacokinetic parameters and their correlation with bacterial killing.
Conclusions:
- Meropenem-vaborbactam HSR profiles can be established in murine models.
- Different HSRs may lead to varying outcomes in bacterial killing.
- Understanding HSRs is key for translating preclinical findings to human clinical use.
