{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:16:25Z","timestamp":1785417385312,"version":"3.56.0"},"reference-count":27,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["853967"],"award-info":[{"award-number":["853967"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,3,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      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\u2014key 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\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      isolates. Fifteen met predefined virulence criteria\u2014showing at least a 1 log\n                      <jats:sub>\u2081\u2080<\/jats:sub>\n                      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 protocol can enhance the reliability and consistency of preclinical efficacy assessments and help reduce the number of animals required, aligning with the 3R principles\u2014reduce, refine, replace\u2014in animal research.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The rise of antibiotic-resistant bacteria has made it increasingly difficult to treat common infections, such as pneumonia. To develop new antibiotics, scientists rely on animal infection models to test how well potential drugs work before human trials. However, inconsistent methods between laboratories make it hard to compare results and slow the progress of new treatments. This study established and validated a standardized mouse pneumonia model for\n                        <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                        and\n                        <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                        \u2014two major pneumonia pathogens\u2014across three international research centers. By identifying and sharing a set of well-characterized bacterial strains and a common experimental protocol, we provide a reliable foundation for comparing drug efficacy data. This model will help improve the quality and reproducibility of preclinical antibiotic research, reduce unnecessary animal use, and accelerate the discovery of new treatments against life-threatening bacterial infections.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.03464-25","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T14:02:31Z","timestamp":1768399351000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["The COMBINE pneumonia model: a multicenter study to standardize a mouse pneumonia model with\n                    <i>Pseudomonas aeruginosa<\/i>\n                    and\n                    <i>Klebsiella pneumoniae<\/i>\n                    for antibiotic development"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6410-5755","authenticated-orcid":true,"given":"Jon U.","family":"Hansen","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0417ye583","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Bacteria, Parasites and Fungi, Statens Serum Institut","place":["Copenhagen, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0757-3915","authenticated-orcid":true,"given":"Rakel","family":"Arrazuria","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00yssnc44","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Microbiology, Paul-Ehrlich-Institut","place":["Langen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6769-7541","authenticated-orcid":true,"given":"Jennifer 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