{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T19:55:22Z","timestamp":1770148522928,"version":"3.49.0"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Intubated patients with methicillin\u2010resistant <jats:styled-content style=\"fixed-case\"><jats:italic>Staphylococcus aureus<\/jats:italic><\/jats:styled-content> pneumonia, fail optimized treatment with intravenous (IV) vancomycin (serum trough 15\u201320\u2009\u03bcg\/mL) in 38\u201379% of cases. Airway blood flow is diminished compared to alveoli and we hypothesized that vancomycin concentrations achieved in airway secretions are suboptimal and nonbactericidal. Targeted therapy by inhalation may overcome this deficit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Airway pharmacokinetics of optimized IV and inhaled vancomycin in infected clinically stable prolonged mechanically ventilated patients were measured. First, IV vancomycin was given until optimized concentrations were achieved (15\u201320\u2009\u03bcg\/mL), and, at the same time point, sputum vancomycin concentrations were measured. Then, sputum concentrations were re\u2010assessed after 4 treatments of inhaled vancomycin (120\u2009mg\/2\u00a0mL) via a previously characterized nebulizing system that deposited 18\u2009\u00b1\u00a02\u00a0mg in the lungs. Vancomycin post\u2010distribution phase serum peak and trough concentrations were also obtained. Serum albumin was measured to assess binding to vancomycin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mean serum trough concentration was 18.4\u00a0\u00b1\u00a06.5\u00a0\u03bcg\/mL. Sputum concentrations were affected by serum albumin. Only patients with severe hypoalbuminaemia had penetration of drug leading to <jats:italic>therapeutic<\/jats:italic> (15.7\u201317\u2009\u03bcg\/mL) sputum concentrations. Following inhaled vancomycin, sputum concentrations increased significantly to 199\u2009\u00b1\u200937.0\u00a0\u03bcg\/mL (<jats:italic>P<\/jats:italic>\u00a0=\u2009.002) exceeding minimum inhibitory concentration by 2 orders of magnitude.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Despite optimized serum concentrations, patients with albumin near normal had suboptimal concentrations of vancomycin in their sputum. Inhaled therapy may be clinically important for successful treatment of ventilator\u2010associated methicillin\u2010resistant <jats:styled-content style=\"fixed-case\"><jats:italic>Staphylococcus aureus<\/jats:italic><\/jats:styled-content> infection. Further studies of inhaled therapy are needed to define their role as adjunctive therapy in ventilator\u2010associated pneumonia and as single therapy in tracheobronchitis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16225","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T11:16:03Z","timestamp":1725534963000},"page":"127-133","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacokinetics of vancomycin in sputum of intubated patients: Optimized intravenous delivery <i>vs<\/i>. inhaled therapy"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1835-968X","authenticated-orcid":false,"given":"Lucy B.","family":"Palmer","sequence":"first","affiliation":[{"name":"Pulmonary, Critical Care and Sleep Division, Department of Medicine Health Sciences Center  Stony Brook NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melinda","family":"Monteforte","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Department of Medicine L3\u2010560 Stony Brook Hospital  Stony Brook NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerald C.","family":"Smaldone","sequence":"additional","affiliation":[{"name":"Pulmonary, Critical Care and Sleep Division, Department of Medicine Health Sciences Center  Stony Brook NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,9,5]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw353"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134\u2010003\u20102088\u20101"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00712\u201011"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01726369"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.37.2.281"},{"issue":"3","key":"e_1_2_14_7_1","first-page":"44","article-title":"Plasma and intrapulmonary concentrations of oritavancin and vancomycin in normal healthy adults","volume":"10","author":"Rodvold KA","year":"2004","journal-title":"Clin Microbiol Infect"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1592\/phco.26.4.539"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.2146\/ajhp080434"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13104\u2010016\u20102252\u20107"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.3947\/ic.2014.46.4.219"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000002824"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix055"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200210\u20101167OC"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajhp\/zxaa128"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.149.1.8111585"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1515\/DMDI.2009.24.2\u20104.259"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e31817c0f9e"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1086\/491712"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/9.4.713"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/2.3.340"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201312\u20102161OC"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.16225","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T02:37:32Z","timestamp":1735267052000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.16225"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,5]]},"references-count":21,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1111\/bcp.16225"],"URL":"https:\/\/doi.org\/10.1111\/bcp.16225","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,5]]}}}