COMBINE Pneumonia Model
The COMBINE project has developed a lung infection model that provides a reproducible and well-characterised experimental framework for evaluating small-molecule antibiotics, along with a repository of virulent bacterial strains.
The model includes a consensus lung infection protocol developed by researchers at Statens Serum Institut (SSI) in Denmark, GSK in the United States and the Paul-Ehrlich-Institut in Germany. Klebsiella pneumoniae and Pseudomonas aeruginosa isolates were tested against predefined virulence criteria, and followed up by independent sites to confirm virulence with minimal variability in bacterial growth. These isolates are now available via the German Collection of Microorganisms and Cell Cultures GmbH (DSMZ) through the IMI COMBINE Preclinical Bacterial Strain Repository (PBSR). Based on this effort, COMBINE has developed a standardised experimental framework using this panel of isolates to enable robust preclinical testing of new antibiotics.
The protocol has standardised key methodological procedures that can influence study outcomes, including the use of available virulent bacterial isolates, animal sex, breed, immune status and age, as well as inoculation techniques. These parameters were discussed with the scientific community before proposing a consensus protocol.
IMI COMBINE Preclinical Bacterial Strain Repository
The IMI COMBINE Preclinical Bacterial Strain Repository consists of well-characterised and virulent strains of the 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.
Contact COMBINE for more information
For more information about the animal model, strain repository and PKPD-studies, please contact:
- Animal model: Jon Ulf Hansen, Statens Serum Institut (SSI)
- Strain repository: Bernhard Kerscher, Paul-Ehrlich-Institut
- PKPD: Lena Friberg, Uppsala University
Publications on the COMBINE Pneumonia Model
The COMBINE Pneumonia Model protocol is described in a paper published in Microbiology Spectrum (2026). Supporting publications include a summary of an expert workshop on parameters for the consensus protocol, and a study exploring the variability of murine pneumonia models.
Describing the model: publications from COMBINE
- 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. 2026. The COMBINE pneumonia model: a multicenter study to standardize a mouse pneumonia model with Pseudomonas aeruginosa and Klebsiella pneumoniae for antibiotic development. Microbiol Spectr 14:e03464-25. Doi: 1128/spectrum.03464-25
- Vera-Yunca D, Matias C, Vingsbo Lundberg C, Friberg LE. Model-based translation of the PKPD-relationship for linezolid and vancomycin on methicillin-resistant Staphylococcus aureus : from in vitrotime–kill experiments to a mouse pneumonia model. Journal of Antimicrobial Chemotherapy. 2025;80(7);1860-1868. doi:10.1093/jac/dkaf140
- Arrazuria R, Kerscher B, Huber KE, et al. Expert workshop summary: Advancing toward a standardized murine model to evaluate treatments for antimicrobial resistance lung infections. Frontiers in Microbiology. 2022;13:988725. doi:10.3389/fmicb.2022.988725
- 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. doi:10.3389/fmicb.2022.988728
Posters
- Vingsbo Lundberg, C., Vera-Yunca, D., Arrazuria, R., Kerscher, B., Hoover, J. L., Tassi, N., Sordello, S., Bekeredjian-Ding, I., Hughes, D., Friberg, L. E., & Hansen, J. U. (2026). The COMBINE Pneumonia Model: Multicenter Confirmation of Virulence (Version v1). 10th AMR Conference: Novel Antimicrobials and AMR Diagnostics, presented at the AMR Conference 2025, Basel, Switzerland. Zenodo. https://doi.org/10.5281/zenodo.19604414
- Matias, C. S., Vera-Yunca, D., Friberg, L. E., Vingsbo Lundberg, C. (2025) Development of a Murine Pneumonia Model with Methicillin-resistant Staphylococcus aureus (MRSA) to Evaluate Antibiotic Treatments, presented at the ESCMID Global 2025, Vienna, Austria. doi: 10.5281/zenodo.17668732
Applying the model: Publications from collaborators
- Fratoni AJ, Padgett AM, Duffy EM, Nicolau DP. Quantitative performance of humanized plasma and epithelial lining fluid exposures of meropenem, cefiderocol and tobramycin against a challenge set of Klebsiella pneumoniae and Pseudomonas aeruginosa in a standardized neutropenic murine pneumonia model. J Antimicrob Chemother. 2025 Jun 3;80(6):1552-1559. doi: 1093/jac/dkaf100.
- Fratoni AJ, Padgett AM, Roenfanz HF, Duffy EM, Nicolau DP. Development and confirmation of humanized plasma and epithelial lining fluid exposures of meropenem, cefiderocol and tobramycin in a standardized neutropenic murine pneumonia model. J Antimicrob Chemother. 2025 Feb 3;80(2):478-484. doi: 10.1093/jac/dkae432.
- Fratoni AJ, Padgett AM, Duffy EM, Nicolau DP. Establishment of a diverse pheno-genotypic challenge set of Klebsiella pneumoniae and Pseudomonas aeruginosa suitable for use in the murine pneumonia model. J Antimicrob Chemother. 2025 Jan 3;80(1):154-161. doi: 10.1093/jac/dkae388..
- Fratoni AJ, Padgett AM, Duffy EM, Nicolau DP. Quantitative performance of humanized serum and epithelial lining fluid exposures of tigecycline and levofloxacin against a challenge set of Klebsiella pneumoniae and Pseudomonas aeruginosa in a standardized neutropenic murine pneumonia model. J Antimicrob Chemother. 2024 Dec 2;79(12):3142-3149. doi: 10.1093/jac/dkae333.
Posters presenting the IMI COMBINE Preclinical Bacterial Strain Repository (PBSR)
- Kerscher, B., Arrazuria, R., Vingsbo Lundberg, C., Hansen, J. U., Hoover, J. L., Sordello, S., Gribbon, P., Hughes, D., Friberg, L. E., Bekeredjian-Ding, I. (2024) The COMBINE Preclinical Bacterial Strain Repository (PBSR): a new resource for preclinical lung infection models to assess antibiotic efficacy, presented at the 8th AMR Conference, Basel, Switzerland.
Posters describing the IMI COMBINE Pneumonia Model
- Matias, C. S., Vera-Yunca, D., Friberg, L. E., Vingsbo Lundberg, C. (2025) Development of a Murine Pneumonia Model with Methicillin-resistant Staphylococcus aureus(MRSA) to Evaluate Antibiotic Treatments, presented at the ESCMID Global 2025, Vienna, Austria.
- Fernow, J., Robijns, C., Vingsbo-Lundberg, C., Deroose, F., Sjöquist, M. (2024) Communicating about animal research in antibiotics drug development, presented at the Uppsala Antibiotic Days, Sweden.
- Vera-Yunca, D., Friberg, L. E. (2024) A multistate model for the analysis of clinical outcomes in nosocomial pneumonia patients, presented at the ESCMID Global 2024, Barcelona, Spain.
- Vingsbo Lundberg, C., Hansen, J. U., Vera, D., Arrazuria, R., Kerscher, B., Hoover, J. L., Sordello, S., Bekeredjian-Ding, I., Hugues, D., Friberg, L. E. (2024) A standard protocol for the murine pneumonia model to investigate antibiotic treatment effect of MDR bacteria infections, presented at the 2024 Gordon Research Conference on Innovative Approaches in Antibacterial Research and Development to Fight the Antibiotic Resistance Crisis, Ventura, United States.
- Vingsbo Lundberg, C., Hansen, J. U., Vera, D., Arrazuria, R., Kerscher, B., Hoover, J. L., Sordello, S., Bekeredjian-Ding, I., Hughes, D., Friberg, L. E. (2023) Evaluation of a standard protocol for the murine pneumonia model to investigate antibiotic treatment effect of infections with MDR Gram negative bacteria, presented at the 2023 Joint ESCMID/ASM Conference, Boston, US.
- Vera-Yunca, D., Friberg, L. E. (2023) A translational semi-mechanistic pharmacokinetic-pharmacodynamic framework to design animal studies: Application to linezolid and vancomycin, presented at 31st PAGE Meeting 2023, Palexco A Coruña, Spain.
- Hansen, J. U., Arrazuria, R., Kerscher, B., Hoover, J. L., Vingsbo Lungberg, C., Sordello, S., Aranzana-Climent, V., Bekeredjian-Ding, I., Hughes, D., Gribbon, P., Friberg, L. E. (2022) A standard protocol for the murine pneumonia model to evaluate treatments for AMR lung infections, presented at the 2022 ESCMID/ASM Joint Conference, Dublin, Ireland, and at the 7th AMR Conference, Basel, Switzerland.
- Vingsbo Lundberg, C., Arrazuria, R., Kerscher, B., Huber, K. E., Hoover, J. L., Hansen, J. U., Sordello, S., Renard, S., Aranzana-Climent, V., Hughes, D., Gribbon, P., Friberg, L. E., Bekeredjian-Ding, I. (2022) A standardized murine pneumonia model to evaluate antibiotic treatments, presented at the Gordon Research Conference on Disruptive Antibiotics and Non-Antibiotic Therapies to Combat Drug-Resistant Bacterial Infections, Lucca, Italy.
