Abstract
Understanding the pharmacokinetics parameter of colistin methanesulfonate sodium (CMS) and colistin is needed to optimize the dosage regimen in critically ill patients. However, there is a scarcity of pharmacokinetics parameters in this population. This review provides a comprehensive understanding of CMS and colistin pharmacokinetics parameters in this population. The relevant studies published in English that reported on the pharmacokinetics of CMS and colistin from 2000 until 2020 were systematically searched using the PubMed and Scopus electronic databases. Reference lists of articles were reviewed to identify additional studies. A total of 252 citation titles were identified, of which 101 potentially relevant abstracts were screened, and 25 full-text articles were selected for detailed analysis. Of those, 15 studies were included for the review. This review has demonstrated vast inter-study discrepancies in colistin plasma concentration and the pharmacokinetics parameter estimates. The discrepancies might be due to complex pathophysiological changes in the population studied, differences in CMS brand used, methodology, and study protocol. Application of loading dose of CMS and an additional dose of CMS after dialysis session was recommended by some studies. In view of inter-patient and intra-patient variability in colistin plasma concentration and pharmacokinetics parameters, personalized colistin dosing for this population is recommended.
Highlights
Colistin is an antibiotic that is used as a last resort to treat infections caused by multidrug-resistant Gram-negative bacteria
A total of 707 patients were enrolled in the pharmacokinetics studies that were conducted from different study sites, such as Greece [3,9,10,20,21], France [11,15,22], Italy [23], Switzerland [14], Israel [2], India [4,5,12], United States of America [6], and Thailand [6]
The use of different colistin methanesulfonate sodium (CMS) formulations may have contributed to the interstudy discrepancies
Summary
Colistin is an antibiotic that is used as a last resort to treat infections caused by multidrug-resistant Gram-negative bacteria. Studies have found inter- and intra-individual variability in the pharmacokinetics of colistin, resulting in extremely varied plasma concentrations following the same dosage schedule [2,3,4,5]. CMS has complex pharmacokinetics and variable bioconversion, in patients with varying degrees of renal function [2,6]. CMS conversion to colistin is slow, while CMS excretion from the body system is high in individuals with good renal function, making it difficult to achieve the desired colistin plasma concentration (2–4 mg/L) [7]. For polymyxin-induced bacterial death, rapid achievement of the desired concentration has been demonstrated to be crucial [8].Earlier pharmacokinetic results revealed that starting colistin therapy with a loading dosage resulted in faster
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