The COMBINE pneumonia model: a multicenter study to standardize a mouse pneumonia model with Pseudomonas aeruginosa and Klebsiella pneumoniae for antibiotic development
Abstract
ABSTRACT The growing threat of antimicrobial resistance highlights the urgent need for new treatment strategies. Reliable animal data are essential to accelerate antibiotic development, and standardized murine infection models, like the neutropenic mouse pneumonia model, can improve the reproducibility and comparability of efficacy data across laboratories—key for clinical translation. This study aims to develop a standardized murine pneumonia model to enhance the clinical relevance of preclinical findings. Using a consensus lung infection protocol, we tested 32 Klebsiella pneumoniae and Pseudomonas aeruginosa isolates. Fifteen met predefined virulence criteria—showing at least a 1 log₁₀ increase in bacterial load from baseline to endpoint, while maintaining mouse survival for at least 12 h post-inoculation. These isolates are available through the German Collection of Microorganisms and Cell Cultures GmbH (DSMZ). Follow-up studies at independent sites confirmed the virulence of eight isolates with minimal variability in bacterial growth. These were added to the Collaboration for Prevention and Treatment of MDR Bacterial Infection (COMBINE Preclinical Bacterial Strain Repository at DSMZ. Based on this work, we propose a standardized experimental framework using this isolate panel to support robust preclinical testing of new antibacterial therapies. This model offers a reproducible, well-characterized platform for evaluating anti-infective candidates. We believe the COMBINE…
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