| Steady-state pharmacokinetics and BAL concentration of colistin in critically Ill patients after IV colistin methanesulfonate administration. | |
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MedLine Citation:
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PMID: 20558557 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Infections caused by multidrug-resistant gram-negative bacteria have caused a resurgence of interest in colistin. To date, information about pharmacokinetics of colistin is very limited in critically ill patients, and no attempts have been made to evaluate its concentration in BAL. METHODS: In this prospective, open-label study, 13 adult patients with ventilator-associated pneumonia caused by gram-negative bacteria were treated with colistin methanesulfonate (CMS) IV, 2 million International Units (174 mg) q8h, a usually recommended dose, for at least 2 days. Blood samples were collected from each patient at time intervals after the end of infusion. BAL was performed at 2 h. Colistin was measured by a selective, sensitive high-performance liquid chromatography-based method. Pharmacokinetic parameters were determined by noncompartmental analysis. RESULTS: Patients received 2.19 ± 0.38 mg/kg (range, 1.58-3.16) of CMS per dose. At steady state, mean ± SD plasma colistin maximum (Cmax) and trough (Ctrough) concentrations were 2.21 ± 1.08 and 1.03 ± 0.69 μg/mL, respectively. Mean ± SD area under the plasma concentration-time curve from 0 to 8 h (AUC(0-8)), apparent elimination half-life, and apparent volume of distribution were 11.5 ± 6.2 μg × h/mL, 5.9 ± 2.6 h, and 1.5 ± 1.1 L/kg, respectively. Cmax/minimum inhibitory concentration (MIC) ratio and AUC(0-24)/MIC ratio (MIC = 2 μg/mL) were 1.1 ± 0.5 and 17.3 ± 9.3, respectively. Colistin was undetectable in BAL. Nephrotoxicity was not observed. CONCLUSIONS: Although the pharmacodynamic parameters that better predict the efficacy of colistin are not known in humans, in critically ill adult patients the IV administration of CMS 2 million International Units (174 mg) q8h results in apparently suboptimal plasma concentrations of colistin, which is undetectable in BAL. A better understanding of the pharmacokinetic-pharmacodynamic relationship of colistin is urgently needed to determine the optimal dosing regimen. |
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Authors:
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Roberto Imberti; Maria Cusato; Paola Villani; Livio Carnevale; Giorgio A Iotti; Martin Langer; Mario Regazzi |
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Publication Detail:
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Type: Journal Article Date: 2010-06-17 |
Journal Detail:
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Title: Chest Volume: 138 ISSN: 1931-3543 ISO Abbreviation: Chest Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-08 Completed Date: 2011-01-13 Revised Date: 2011-01-21 |
Medline Journal Info:
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Nlm Unique ID: 0231335 Medline TA: Chest Country: United States |
Other Details:
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Languages: eng Pagination: 1333-9 Citation Subset: AIM; IM |
Affiliation:
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Direzione Scientifica, Fondazione IRCCS Policlinco S. Matteo 27100 Pavia, Italy. r.imberti@smatteo.pv.it |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Anti-Bacterial Agents / pharmacokinetics*, therapeutic use Bronchoalveolar Lavage Fluid / chemistry* Colistin / pharmacokinetics*, therapeutic use Critical Illness Dose-Response Relationship, Drug Drug Administration Schedule Female Follow-Up Studies Gram-Negative Bacteria / drug effects Gram-Negative Bacterial Infections / diagnosis, drug therapy* Humans Infusions, Intravenous Intensive Care Units Male Middle Aged Pneumonia, Ventilator-Associated / diagnosis, drug therapy*, mortality Prospective Studies Survival Rate Treatment Outcome Young Adult |
| Chemical | |
Reg. No./Substance:
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0/Anti-Bacterial Agents; 1066-17-7/Colistin |
| Comments/Corrections | |
Comment In:
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Chest. 2011 Jan;139(1):234; author reply 234-5
[PMID:
21208893
]
Chest. 2011 Jan;139(1):232-3; author reply 233-4 [PMID: 21208892 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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