{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:54:04Z","timestamp":1790650444368,"version":"4.1.0"},"reference-count":73,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T00:00:00Z","timestamp":1685491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Hospital-acquired pneumonia, including ventilator-associated pneumonia (VAP) due to difficult-to-treat-resistant (DTR) Gram-negative bacteria, contributes significantly to morbidity and mortality in ICUs. In the era of COVID-19, the incidences of secondary nosocomial pneumonia and the demand for invasive mechanical ventilation have increased dramatically with extremely high attributable mortality. Treatment options for DTR pathogens are limited. Therefore, an increased interest in high-dose nebulized colistin methanesulfonate (CMS), defined as a nebulized dose above 6 million IU (MIU), has come into sight. Herein, the authors present the available modern knowledge regarding high-dose nebulized CMS and current information on pharmacokinetics, clinical studies, and toxicity issues. A brief report on types of nebulizers is also analyzed. High-dose nebulized CMS was administrated as an adjunctive and substitutive strategy. High-dose nebulized CMS up to 15 MIU was attributed with a clinical outcome of 63%. High-dose nebulized CMS administration offers advantages in terms of efficacy against DTR Gram-negative bacteria, a favorable safety profile, and improved pharmacokinetics in the treatment of VAP. However, due to the heterogeneity of studies and small sample population, the apparent benefit in clinical outcomes must be proven in large-scale trials to lead to the optimal use of high-dose nebulized CMS.<\/jats:p>","DOI":"10.3390\/microorganisms11061459","type":"journal-article","created":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T01:40:56Z","timestamp":1685583656000},"page":"1459","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["High-Dose Nebulized Colistin Methanesulfonate and the Role in Hospital-Acquired Pneumonia Caused by Gram-Negative Bacteria with Difficult-to-Treat Resistance: A Review"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2226-0239","authenticated-orcid":false,"given":"Ilias","family":"Karaiskos","sequence":"first","affiliation":[{"name":"First Department of Internal Medicine-Infectious Diseases, Hygeia General Hospital, 4, Erythrou Stavrou Str. & Kifisias, 15123 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5644-8208","authenticated-orcid":false,"given":"Aikaterini","family":"Gkoufa","sequence":"additional","affiliation":[{"name":"Infectious Diseases and COVID-19 Unit, Medical School, Laiko General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Polyzou","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Patras, 26504 Patras, Greece"},{"name":"Department of Internal Medicine and Infectious Diseases, University General Hospital of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7963-1865","authenticated-orcid":false,"given":"Georgios","family":"Schinas","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe","family":"Athanassa","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, Sismanoglio General Hospital, 15126 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4289-9494","authenticated-orcid":false,"given":"Karolina","family":"Akinosoglou","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Patras, 26504 Patras, Greece"},{"name":"Department of Internal Medicine and Infectious Diseases, University General Hospital of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e61","DOI":"10.1093\/cid\/ciw353","article-title":"Management of Adults with Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society","volume":"63","author":"Kalil","year":"2016","journal-title":"Clin. 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