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However, intravenous (IV) antibiotics often achieve suboptimal pulmonary concentrations. We therefore aimed to evaluate the effect of inhaled amikacin (AMK) plus IV meropenem (MEM) on bactericidal efficacy in a swine model of monolateral MDR <jats:italic>P. aeruginosa<\/jats:italic> pneumonia.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We ventilated 18 pigs with monolateral MDR <jats:italic>P. aeruginosa<\/jats:italic> pneumonia for up to 102\u00a0h. At 24\u00a0h after the bacterial challenge, the animals were randomized to receive 72\u00a0h of treatment with either inhaled saline (control), IV MEM only, or IV-MEM plus inhaled AMK (MEM\u2009+\u2009AMK). We dosed IV MEM at 25\u00a0mg\/kg every 8\u00a0h and inhaled AMK at 400\u00a0mg every 12\u00a0h. The primary outcomes were the <jats:italic>P. aeruginosa<\/jats:italic> burden and histopathological injury in lung tissue. Secondary outcomes included the <jats:italic>P. aeruginosa<\/jats:italic> burden in tracheal secretions and bronchoalveolar lavage fluid, the development of antibiotic resistance, the antibiotic distribution, and the levels of inflammatory markers.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The median (25\u201375th percentile) <jats:italic>P. aeruginosa<\/jats:italic> lung burden for animals in the control, MEM only, and MEM\u2009+\u2009AMK groups was 2.91 (1.75\u20135.69), 0.72 (0.12\u20133.35), and 0.90 (0\u20134.55) log<jats:sub>10<\/jats:sub> CFU\/g (<jats:italic>p<\/jats:italic>\u2009=\u20090.009). Inhaled therapy had no effect on preventing dissemination compared to systemic monotherapy, but it did have significantly higher bactericidal efficacy in tracheal secretions only. Remarkably, the minimum inhibitory concentration of MEM increased to\u2009&gt;\u200932\u00a0mg\/L after 72-h exposure to monotherapy in 83% of animals, while the addition of AMK prevented this increase (<jats:italic>p<\/jats:italic>\u2009=\u20090.037). Adjunctive therapy also slightly affected interleukin-1\u03b2 downregulation. Despite finding high AMK concentrations in pulmonary samples, we found no paired differences in the epithelial lining fluid concentration between infected and non-infected lungs. Finally, a non-significant trend was observed for higher amikacin penetration in low-affected lung areas.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In a swine model of monolateral MDR <jats:italic>P. aeruginosa<\/jats:italic> pneumonia, resistant to the inhaled AMK and susceptible to the IV antibiotic, the use of AMK as an adjuvant treatment offered no benefits for either the colonization of pulmonary tissue or the prevention of pathogen dissemination. However, inhaled AMK improved bacterial eradication in the proximal airways and hindered antibiotic resistance.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13054-023-04331-x","type":"journal-article","created":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T14:05:11Z","timestamp":1676383511000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Inhaled amikacin for pneumonia treatment and dissemination prevention: an experimental model of severe monolateral Pseudomonas aeruginosa pneumonia"],"prefix":"10.1186","volume":"27","author":[{"given":"Ana","family":"Motos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluigi","family":"Li Bassi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minlan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Meli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Battaglini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Cabrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquim","family":"Bobi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Pagliara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Frigola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Camprub\u00ed-Rimblas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laia","family":"Fern\u00e1ndez-Barat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montserrat","family":"Rigol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoni","family":"Ferrer-Segarra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasra","family":"Kiarostami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Martinez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Nicolau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Artigas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Pelosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Vila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoni","family":"Torres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,2,14]]},"reference":[{"issue":"3","key":"4331_CR1","doi-asserted-by":"publisher","first-page":"1700582","DOI":"10.1183\/13993003.00582-2017","volume":"50","author":"A Torres","year":"2017","unstructured":"Torres A, Niederman MS, Chastre J, Ewig S, Fernandez-Vandellos P, Hanberger H, et al. 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Documented approval from University of Barcelona Institutional Review Board was obtained prior to the study started (number approval 9772).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"A. Torres and G. Li Bassi received an unrestrictive grant from Bayer AG (Berlin, Germany) through their affiliated institution. Bayer AG, the manufacturer of inhaled amikacin, provided funds to support this research. Bayer AG had no role in the data collection, data analysis, or data interpretation. Bayer AG reviewed the final manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interest"}}],"article-number":"60"}}