Data for study "A Multicenter Study to Standardize a Mouse Pneumonia Model with Pseudomonas aeruginosa and Klebsiella pneumoniae for Antibiotic Development"

The rise of antimicrobial resistance (AMR) underscores the urgent need for new therapeutic strategies. Reliable animal data is crucial for accelerating antibiotic development, and standardized murine infection models, such as the neutropenic mouse pneumonia model, could be key to enabling the generation of efficacy data with improved reproducibility and comparability among different laboratories. Improving reproducibility is essential for enhancing clinical translation. This study aims to establish a standardized murine pneumonia model to enhance the translation of preclinical findings into clinical applications. 

Using a consensus lung infection protocol, we tested 32 Klebsiella pneumoniae and Pseudomonas aeruginosa strains. Fifteen strains met our predefined virulence criteria—demonstrating at least a one log₁₀ increase in bacterial load from baseline to endpoint while sustaining mouse survival for at least 12 hours post-inoculation. These strains are deposited at the German Collection of Microorganisms and Cell Cultures GmbH (DSMZ) and available to researchers.

Further studies at two or three independent sites (depending on strain) confirmed the virulence of eight strains, showing minimal variability in bacterial growth. These strains were incorporated into the COMBINE Preclinical Bacterial Strain Repository (PBSR) held at DSMZ. Based on these findings, we propose standardized experimental conditions, together with this defined strain panel, as a robust murine pneumonia model for preclinical testing of novel antibacterial therapies. This model provides a reproducible and well-characterized foundation for evaluating new anti-infective candidates. Ultimately, we believe the COMBINE protocol can improve the reliability and comparability of preclinical efficacy testing, and potentially reduce the number of animals needed, thus also contributing to the 3R (reduce, refine, replace) principles in animal welfare.

COMBINE Pneumonia Model resources

• COMBINE preclinical repository with bacterial strains found to be reproducibly virulent and fulfilling performance criteria in the COMBINE standardised pneumonia mouse model.
• Data from the COMBINE Multicenter Study to Standardize a Mouse Pneumonia Model with Pseudomonas aeruginosa and Klebsiella pneumoniae for Antibiotic Development  
• Arrazuria R, Kerscher B, Huber KE, Hoover JL, Lundberg CV, Hansen JU, Sordello S, Renard S, Aranzana-Climent V, Hughes D, Gribbon P, Friberg LE, Bekeredjian-Ding I (2022): Expert workshop summary: Advancing toward a standardized murine model to evaluate treatments for antimicrobial resistance lung infections.
  Front Microbiol 13: 988725.
• Arrazuria R, Kerscher B, Huber KE, et al. Variability of murine bacterial pneumonia models used to evaluate antimicrobial agents. Frontiers in Microbiology. 2022;13:988728.