Population pharmacokinetics of colistin methanesulfonate and formed colistin in critically ill patients from a multicenter study provide dosing suggestions for various categories of patients

Garonzik, S.M., Li, J., Thamlikitkul, V., Paterson, D.L., Shoham, S., Jacob, J., Silveira, F.P., Forrest, A. and Nation, R.L. (2011) Population pharmacokinetics of colistin methanesulfonate and formed colistin in critically ill patients from a multicenter study provide dosing suggestions for various categories of patients. Antimicrobial Agents and Chemotherapy, 55 7: 3284-3294. doi:10.1128/AAC.01733-10

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Author Garonzik, S.M.
Li, J.
Thamlikitkul, V.
Paterson, D.L.
Shoham, S.
Jacob, J.
Silveira, F.P.
Forrest, A.
Nation, R.L.
Title Population pharmacokinetics of colistin methanesulfonate and formed colistin in critically ill patients from a multicenter study provide dosing suggestions for various categories of patients
Journal name Antimicrobial Agents and Chemotherapy   Check publisher's open access policy
ISSN 0066-4804
1098-6596
Publication date 2011-07-01
Year available 2011
Sub-type Article (original research)
DOI 10.1128/AAC.01733-10
Open Access Status File (Publisher version)
Volume 55
Issue 7
Start page 3284
End page 3294
Total pages 11
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Abstract With increasing clinical emergence of multidrug-resistant Gram-negative pathogens and the paucity of new agents to combat these infections, colistin (administered as its inactive prodrug colistin methane-sulfonate [CMS]) has reemerged as a treatment option, especially for critically ill patients. There has been a dearth of pharmacokinetic (PK) data available to guide dosing in critically ill patients, including those on renal replacement therapy. In an ongoing study to develop a population PK model for CMS and colistin, 105 patients have been studied to date; these included 12 patients on hemodialysis and 4 on continuous renal replacement therapy. For patients not on renal replacement, there was a wide variance in creatinine clearance, ranging from 3 to 169 ml/min/1.73 m 2. Each patient was treated with a physician-selected CMS dosage regimen, and 8 blood samples for PK analysis were collected across a dosage interval on day 3 or 4 of therapy. A linear PK model with two compartments for CMS and one compartment for formed colistin best described the data. Covariates included creatinine clearance on the total clearance of CMS and colistin, as well as body weight on the central volume of CMS. Model-fitted parameter estimates were used to derive suggested loading and maintenance dosing regimens for various categories of patients, including those on hemodialysis and continuous renal replacement. Based on our current understanding of colistin PK and pharmacodynamic relationships, colistin may best be used as part of a highly active combination, especially for patients with moderate to good renal function and/or for organisms with MICs of ≥1.0 mg/liter.
Keyword Microbiology
Pharmacology & Pharmacy
Microbiology
Pharmacology & Pharmacy
MICROBIOLOGY
PHARMACOLOGY & PHARMACY
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID R01AI070896
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2012 Collection
School of Medicine Publications
 
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Created: Wed, 05 Oct 2011, 21:26:30 EST by Matthew Lamb on behalf of School of Medicine