{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T00:16:28Z","timestamp":1769300188913,"version":"3.49.0"},"reference-count":25,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Ventilator-associated bacterial pneumonia (VABP) is among the most intractable of carbapenem-resistant Gram-negative bacterial infections. New antimicrobial agents are critically needed for the treatment of VABP. However, current conventionally used animal model systems are inadequate to meet this challenge. We, therefore, developed rabbit models of VABP caused by carbapenem-resistant\n              <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n              . Persistently neutropenic New Zealand White rabbits were used throughout the study. The early-phase intubated model (0\u201324 h) received mechanical ventilation, while the late-phase intubated model (72\u201396 h) was ambulatory. The following outcome parameters were studied: survival, residual tissue bacterial burden (CFU\/g), residual BAL bacterial burden (CFU\/mL), lung weights, pulmonary lesion score, histology, O\n              <jats:sub>2<\/jats:sub>\n              saturation, radiographic imaging, and histology. Each anesthetized rabbit received a predetermined endotracheal bacterial inoculum, and ventilators were set to FiO\n              <jats:sub>2<\/jats:sub>\n              = 40% and PEEP = 8 mmHg. Within the first 12 h post-inoculation, mean bacterial burdens in lung tissue and BAL fluid, respectively, were established at approximately 10\n              <jats:sup>7<\/jats:sup>\n              CFU\/g and 10\n              <jats:sup>6<\/jats:sup>\n              CFU\/mL, persisted through 24 h in the early-phase model and increased in the late-phase model to approximately 10\n              <jats:sup>8<\/jats:sup>\n              CFU\/g and 10\n              <jats:sup>7<\/jats:sup>\n              CFU\/mL. Mean max SpO\n              <jats:sub>2<\/jats:sub>\n              was \u226598 mmHg, and mean nadir SpO\n              <jats:sub>2<\/jats:sub>\n              was \u226568 mmHg. Serial thoracic radiographs demonstrated progressive multilobar pneumonic infiltrates. Lung histology revealed progressive focal bronchopneumonia, coagulative necrosis, intra-alveolar hemorrhage, alveolar epithelial cell necrosis, and bacterial microcolonies. The new rabbit model of VABP produced by carbapenem-resistant\n              <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n              recapitulates the pathophysiological, microbiological, diagnostic imaging, and histological patterns of human disease by which to assess critically needed new antimicrobial agents against this lethal infection.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.00205-24","type":"journal-article","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T13:02:07Z","timestamp":1714482127000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Development of rabbit models of ventilator-associated bacterial pneumonia produced by carbapenem-resistant\n            <i>Pseudomonas aeruginosa<\/i>"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6811-4467","authenticated-orcid":true,"given":"Vidmantas","family":"Petraitis","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, New York, New York, USA"},{"name":"The Biological Research Center, Lithuanian University of Health Sciences, Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3269-8058","authenticated-orcid":true,"given":"Ruta","family":"Petraitiene","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, New York, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Povilas","family":"Kavaliauskas","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, New York, New York, USA"},{"name":"The Biological Research Center, Lithuanian University of Health Sciences, Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ethan","family":"Naing","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, New York, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Garcia","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, New York, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vilma","family":"Zigmantaite","sequence":"additional","affiliation":[{"name":"The Biological Research Center, Lithuanian University of Health Sciences, Kaunas, Lithuania"},{"name":"Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramune","family":"Grigaleviciute","sequence":"additional","affiliation":[{"name":"The Biological Research Center, Lithuanian University of Health Sciences, Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrius","family":"Kucinskas","sequence":"additional","affiliation":[{"name":"The Biological Research Center, Lithuanian University of Health Sciences, Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alius","family":"Pockevicius","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, Veterinary Academy, Pathology Center, Lithuanian University of Health Sciences, Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rimantas","family":"Stakauskas","sequence":"additional","affiliation":[{"name":"The Biological Research Center, Lithuanian University of Health Sciences, Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4142-8711","authenticated-orcid":true,"given":"Thomas J.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, New York, New York, USA"},{"name":"Center for Innovative Therapeutics and Diagnostics, Richmond, Virginia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","published-online":{"date-parts":[[2024,4,30]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu612"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40121-017-0146-1"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/tid.12762"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw243"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx483"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw113"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix893"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu052"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02157-19"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00618-22"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00344-19"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00527-22"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2015.05.004"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200900768"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/379333a0"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113540"},{"key":"e_1_3_2_18_2","first-page":"982","article-title":"The 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The pathology of experimental anthrax in rabbits exposed by inhalation and subcutaneous inoculation. Arch Pathol Lab Med 122:982\u2013992.","journal-title":"Arch Pathol Lab Med"},{"key":"e_1_3_2_19_2","first-page":"467","article-title":"Chronic Silastic central venous catheterization for induction, maintenance and support of persistent granulocytopenia in rabbits","volume":"38","author":"Walsh TJ","year":"1988","unstructured":"Walsh TJ, Bacher J, Pizzo PA. 1988. Chronic Silastic central venous catheterization for induction, maintenance and support of persistent granulocytopenia in rabbits. 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National Academy Press, Washington."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00205-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00205-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T13:02:11Z","timestamp":1714482131000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00205-24"}},"subtitle":[],"editor":[{"given":"Anne-Catrin","family":"Uhlemann","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,4,30]]},"references-count":25,"alternative-id":["10.1128\/aac.00205-24"],"URL":"https:\/\/doi.org\/10.1128\/aac.00205-24","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,30]]},"assertion":[{"value":"2024-02-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00205-24"}}