Nebulized Colistin in Ventilator-Associated Pneumonia and Tracheobronchitis: Historical Background, Pharmacokinetics and Perspectives

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Institut Català de la Salut
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[Zhu Y] Department of Pulmonary and Critical Care Medicine, Hua-Dong Hospital, Fudan University, Shanghai 200433, China. [Monsel A] Multidisciplinary Intensive Care Unit, Department of Anaesthesiology and Critical Care, La Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, Medicine Sorbonne University, 75012 Paris, France. Unité Mixte de Recherche (UMR)-S 959, Immunology-Immunopathology-Immunotherapy (I3), Institut National de la Santé et de la Recherche Médicale (INSERM), 75012 Paris, France. Biotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 75012 Paris, France. [Roberts JA] Biotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 75012 Paris, France. University of Queensland Centre for Clinical Research, Faculty of Medicine The University of Queensland, 4006 Brisbane, Australia. Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women’s Hospital, 4006 Brisbane, Australia. Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, 30029 Nîmes, France. [Pontikis K] Intensive Care Unit, First Department of Respiratory Medicine, School of Medicine, Sotiria General Hospital, National and Kapodistrian University of Athens, 15772 Athens, Greece. [Mimoz O] Anaesthesiology and Intensive Care Department, University Hospital of Poitiers, University of Poitiers, 86000 Poitiers, France. [Rello J] Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain. Recerca Clínica/Innovació en la Pneumònia i Sèpsia (CRIPS), Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Clinical Research, CHU Nîmes, Université Montpellier-Nîmes, 30029 Nîmes, France
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Vall d'Hebron Barcelona Hospital Campus
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Zhu, Yinggang
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Monsel, Antoine
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Roberts, Jason A.
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Pontikis, Konstantinos
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Mimoz, Olivier
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Rello Condomines, Jordi
dc.date.accessioned
2025-10-24T08:52:42Z
dc.date.available
2025-10-24T08:52:42Z
dc.date.issued
2021-12-16T12:32:23Z
dc.date.issued
2021-12-16T12:32:23Z
dc.date.issued
2021-05-27
dc.identifier
Zhu Y, Monsel A, Roberts J, Pontikis K, Mimoz O, Rello J, et al. Nebulized Colistin in Ventilator-Associated Pneumonia and Tracheobronchitis: Historical Background, Pharmacokinetics and Perspectives. Microorganisms. 2021 May 27;9(6):1154.
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2076-2607
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https://hdl.handle.net/11351/6700
dc.identifier
10.3390/microorganisms9061154
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34072189
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000666104300001
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http://hdl.handle.net/11351/6700
dc.description.abstract
Colistin; Phramacokinetic; Technique of nebulization
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Colistina; Farmacocinètica; Tècnica de nebulització
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Colistina; Farmacocinético; Técnica de nebulización
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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 20–25% 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 > 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/ß-lactamase inhibitors in patients with extensive drug-resistant GNB ventilator-associated pneumonia and ventilator-associated tracheobronchitis.
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This research received no external funding.
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application/pdf
dc.language
eng
dc.publisher
MDPI
dc.relation
Microorganisms;9(6)
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https://doi.org/10.3390/microorganisms9061154
dc.rights
Attribution 4.0 International
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http://creativecommons.org/licenses/by/4.0/
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info:eu-repo/semantics/openAccess
dc.source
Scientia
dc.subject
Pneumònia - Tractament
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Medicaments antibacterians - Ús terapèutic
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Malalties bacterianes gramnegatives - Tractament
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DISEASES::Bacterial Infections and Mycoses::Infection::Cross Infection::Pneumonia, Ventilator-Associated
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Other subheadings::Other subheadings::Other subheadings::/drug therapy
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CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial Agents
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Other subheadings::Other subheadings::Other subheadings::/administration & dosage
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ENFERMEDADES::infecciones bacterianas y micosis::infección::infección hospitalaria::neumonía asociada al ventilador
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Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
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COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antibacterianos
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Otros calificadores::Otros calificadores::Otros calificadores::/administración & dosificación
dc.title
Nebulized Colistin in Ventilator-Associated Pneumonia and Tracheobronchitis: Historical Background, Pharmacokinetics and Perspectives
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion


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