The COMBINE Pneumonia Model: Multicenter Confirmation of Virulence

Background and Introduction

• Reliable pre-clinical efficacy data generated in animal infection models is essential to accelerate antibiotic development. Standardized murine infection models can improve the reproducibility and comparability of efficacy data across laboratories.   
• This study establishes and validates the performance of a standardized murine pneumonia model with Klebsiella pneumoniae and Pseudomonas aeruginosa isolates using a consensus lung infection protocol across 3 independent laboratories. 

Results

• 4 K. pneumoniae isolates and 4 P. aeruginosa isolates, displayed reproducible in-vivo performance at all 3 laboratories with >1 log₁₀ CFU increase from baseline to endpoint while maintaining mouse survival for at least 12 hours post-inoculation.
• These 8 isolates are now available to the research community from the COMBINE Preclinical Bacterial Strain Repository (PBSR) at PEI and distributed by DSMZ. 

K. pneumoniae

• Uniform in vivo growth
• No lag phase
• increasing 0.6–1.6 log₁₀ CFU at 8 h
• peaking at ~9 log₁₀ CFU by 26 h
• survived 26-hour

P. aeruginosa

• Heterogeneous growth kinetics
• Lag phase
• Inter-experiment variability
• Reached the humane endpoint between 10–18 h

COMBINE Pneumonia Model

The COMBINE pneumonia model and related resources are described in Hansen JU, Arrazuria R, Hoover JL, Kerscher B, Huseby DL, Sordello S, Gribbon P, Gadiya Y, Berlin Lv, Witt G, Tassi N, Rosenborg F, Cao S, Bekeredjian-Ding I, Lindahl O, Hughes D, Friberg LE, Vingsbo Lundberg C. The COMBINE pneumonia model: a multicenter study to standardize a mouse pneumonia model with Pseudomonas aeruginosa and Klebsiella pneumoniae for antibiotic development. Microbiol Spectr. 2026 Jan 14:e0346425. doi: 10.1128/spectrum.03464-25. 

IMI-COMBINE Preclinical Bacterial Strain Repository

The IMI COMBINE Preclinical Bacterial Strain Repository consists of well-characterised and virulent strains of Gram-negative bacteria Klebsiella pneumoniae and Pseudomonas aeruginosa. The repository is part of a collection of reference materials hosted on the website of the Paul-Ehrlich-Institut, the German Federal Institute for Vaccines and Biomedicines. The strains have been deposited to the German Collection of Microorganisms and Cell Cultures (DSMZ), where they can be ordered for distribution.