{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:19:03Z","timestamp":1787062743111,"version":"build-2736575974"},"reference-count":104,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T00:00:00Z","timestamp":1622073600000},"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>Clinical evidence suggests that nebulized colistimethate sodium (CMS) has benefits for treating lower respiratory tract infections caused by multidrug-resistant Gram-negative bacteria (GNB). Colistin is positively charged, while CMS is negatively charged, and both have a high molecular mass and are hydrophilic. These physico-chemical characteristics impair crossing of the alveolo-capillary membrane but enable the disruption of the bacterial wall of GNB and the aggregation of the circulating lipopolysaccharide. Intravenous CMS is rapidly cleared by glomerular filtration and tubular excretion, and 20\u201325% is spontaneously hydrolyzed to colistin. Urine colistin is substantially reabsorbed by tubular cells and eliminated by biliary excretion. Colistin is a concentration-dependent antibiotic with post-antibiotic and inoculum effects. As CMS conversion to colistin is slower than its renal clearance, intravenous administration can lead to low plasma and lung colistin concentrations that risk treatment failure. Following nebulization of high doses, colistin (200,000 international units\/24h) lung tissue concentrations are &gt; five times minimum inhibitory concentration (MIC) of GNB in regions with multiple foci of bronchopneumonia and in the range of MIC breakpoints in regions with confluent pneumonia. Future research should include: (1) experimental studies using lung microdialysis to assess the PK\/PD in the interstitial fluid of the lung following nebulization of high doses of colistin; (2) superiority multicenter randomized controlled trials comparing nebulized and intravenous CMS in patients with pandrug-resistant GNB ventilator-associated pneumonia and ventilator-associated tracheobronchitis; (3) non-inferiority multicenter randomized controlled trials comparing nebulized CMS to intravenous new cephalosporines\/\u00df-lactamase inhibitors in patients with extensive drug-resistant GNB ventilator-associated pneumonia and ventilator-associated tracheobronchitis.<\/jats:p>","DOI":"10.3390\/microorganisms9061154","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T23:16:46Z","timestamp":1622157406000},"page":"1154","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Nebulized Colistin in Ventilator-Associated Pneumonia and Tracheobronchitis: Historical Background, Pharmacokinetics and Perspectives"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7416-548X","authenticated-orcid":false,"given":"Yinggang","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Hua-Dong Hospital, Fudan University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Monsel","sequence":"additional","affiliation":[{"name":"Multidisciplinary Intensive Care Unit, Department of Anaesthesiology and Critical Care, La Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Assistance Publique H\u00f4pitaux de Paris, Medicine Sorbonne University, 75012 Paris, France"},{"name":"Unit\u00e9 Mixte de Recherche (UMR)-S 959, Immunology-Immunopathology-Immunotherapy (I3), Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), 75012 Paris, France"},{"name":"Biotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Assistance Publique-H\u00f4pitaux de Paris, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6218-435X","authenticated-orcid":false,"given":"Jason","family":"Roberts","sequence":"additional","affiliation":[{"name":"Biotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Assistance Publique-H\u00f4pitaux de Paris, 75012 Paris, France"},{"name":"University of Queensland Centre for Clinical Research, Faculty of Medicine The University of Queensland, 4006 Brisbane, Australia"},{"name":"Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women\u2019s Hospital, 4006 Brisbane, Australia"},{"name":"Division of Anaesthesiology Critical Care Emergency and Pain Medicine, N\u00eemes University Hospital, University of Montpellier, 30029 N\u00eemes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Pontikis","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, First Department of Respiratory Medicine, School of Medicine, Sotiria General Hospital, National and Kapodistrian University of Athens, 15772 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Mimoz","sequence":"additional","affiliation":[{"name":"Anaesthesiology and Intensive Care Department, University Hospital of Poitiers, University of Poitiers, 86000 Poitiers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Rello","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Research & Innovation in Pneumonia & Sepsis, Vall d\u2019Hebron Institute of Research (VHIR), 08035 Barcelona, Spain"},{"name":"Clinical Research, CHU N\u00eemes, Universit\u00e9 Montpellier-N\u00eemes, 30029 N\u00eemes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieming","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Rui-jin Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai 200127, China"},{"name":"Institute of Respiratory Disease, Shanghai Jiao-tong University School of Medicine, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Jacques","family":"Rouby","sequence":"additional","affiliation":[{"name":"Multidisciplinary Intensive Care Unit, Department of Anaesthesiology and Critical Care, La Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Assistance Publique H\u00f4pitaux de Paris, Medicine Sorbonne University, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the European Investigator Network for Nebulized Antibiotics in Ventilator-Associated Pneumonia (ENAVAP)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/160263a0","article-title":"\u201cAerosporin\u201d, an Antibiotic Produced by Bacillus aerosporus Greer","volume":"159","author":"Ainsworth","year":"1947","journal-title":"Nature"},{"key":"ref_2","unstructured":"World Health Organization (2012). 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