Variability of murine bacterial pneumonia models used to evaluate antimicrobial agents
Rakel Arrazuria1, Bernhard Kerscher1, Karen E Huber1
1Division of Microbiology, Paul-Ehrlich-Institut, Langen, Germany.
Abstract:
Antimicrobial resistance has become one of the greatest threats to human health, and new antibacterial treatments are urgently needed. As a tool to develop novel therapies, animal models are essential to bridge the gap between preclinical and clinical research. However, despite common usage of in vivo models that mimic clinical infection, translational challenges remain high. Standardization of in vivo models is deemed necessary to improve the robustness and reproducibility of preclinical studies and thus translational research. The European Innovative Medicines Initiative (IMI)-funded "Collaboration for prevention and treatment of MDR bacterial infections" (COMBINE) consortium, aims to develop a standardized, quality-controlled murine pneumonia model for preclinical efficacy testing of novel anti-infective candidates and to improve tools for the translation of preclinical data to the clinic. In this review of murine pneumonia model data published in the last 10 years, we present our findings of considerable variability in the protocols employed for testing the efficacy of antimicrobial compounds using this in vivo model. Based on specific inclusion criteria, fifty-three studies focusing on antimicrobial assessment against Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii were reviewed in detail. The data revealed marked differences in the experimental design of the murine pneumonia models employed in the literature. Notably, several differences were observed in variables that are expected to impact the obtained results, such as the immune status of the animals, the age, infection route and sample processing, highlighting the necessity of a standardized model.
Insights
Standardizing animal models for antibacterial research is crucial. This review highlights significant variability in murine pneumonia models, hindering the development of new treatments for antimicrobial resistance.
Area of Science:
- Infectious Diseases
- Microbiology
- Pharmacology
Background:
- Antimicrobial resistance (AMR) poses a significant global health threat, necessitating novel antibacterial therapies.
- Animal models are vital for preclinical research, bridging the gap to clinical applications, but face translational challenges.
- Standardization of *in vivo* models is essential for enhancing the reproducibility and reliability of preclinical studies.
Purpose of the Study:
- To review and analyze the variability in murine pneumonia models used for antimicrobial efficacy testing.
- To identify key differences in experimental protocols that impact the translation of preclinical data.
- To underscore the need for a standardized, quality-controlled murine pneumonia model for developing new anti-infective treatments.
Main Methods:
- A systematic review of 53 studies published in the last 10 years focusing on antimicrobial assessment against *Pseudomonas aeruginosa*, *Klebsiella pneumoniae*, and *Acinetobacter baumannii*.
- Inclusion criteria were applied to select studies utilizing murine pneumonia models for antimicrobial compound efficacy testing.
- Detailed analysis of experimental design variables, including animal immune status, age, infection route, and sample processing.
Main Results:
- Considerable variability was found in the protocols of murine pneumonia models used in published studies.
- Significant differences were observed in critical experimental parameters such as animal immune status, age, infection route, and sample processing.
- These protocol variations impact the robustness and reproducibility of antimicrobial efficacy testing.
Conclusions:
- The current lack of standardization in murine pneumonia models presents a significant hurdle for translational research in antibacterial drug development.
- A standardized, quality-controlled murine pneumonia model is urgently needed to improve the reliability of preclinical efficacy testing.
- Standardization efforts, like those by the COMBINE consortium, are critical for advancing the development of novel anti-infective therapies to combat antimicrobial resistance.
