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Original Research: CRITICAL CARE MEDICINE |

Steady-State Pharmacokinetics and BAL Concentration of Colistin in Critically Ill Patients After IV Colistin Methanesulfonate Administration

Roberto Imberti, MD; Maria Cusato, PharmD; Paola Villani, BiolD; Livio Carnevale, MD; Giorgio A. Iotti, MD; Martin Langer, MD; Mario Regazzi, PharmD
Author and Funding Information

Fom the Direzione Scientifica (Dr Imberti), Laboratory of Clinical Pharmacokinetics (Drs Cusato, Villani, and Regazzi), Department of Anesthesiology and Critical Care Medicine (Drs Carnevale and Iotti), Fondazione IRCCS Policlinico S. Matteo, Pavia; Department of Anesthesiology, Intensive Care, and Dermatological Sciences (Dr Langer), Università degli Studi, Milano; and Department of Anesthesiology and Critical Care Medicine (Dr Langer), Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.

Correspondence to: Roberto Imberti, MD, Direzione Scientifica, Fondazione IRCCS Policlinco S. Matteo 27100 Pavia, Italy; e-mail: r.imberti@smatteo.pv.it


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;138(6):1333-1339. doi:10.1378/chest.10-0463
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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 (AUC0-8), 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 AUC0-24/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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