Chest
Original ResearchCritical Care MedicineSteady-State Pharmacokinetics and BAL Concentration of Colistin in Critically Ill Patients After IV Colistin Methanesulfonate Administration
Section snippets
Study Population
The pharmacokinetics and concentration of colistin in BAL were evaluated in 13 adult patients (aged 20-70 years; 10 men, three women) who during their ICU stay developed ventilator-associated pneumonia caused by A baumannii (11 patients) and P aeruginosa (two patients). In nine patients, Acinetobacter was multidrug resistant. Patients with creatinine clearance < 80 mL/min were excluded. The creatinine clearance was calculated according to the formula ClCr = UCr × V/PCr, where UCr is the
Pharmacokinetics of Colistin
The mean ± SD dose of CMS administered, calculated from the most accurate approximation of each patient's weight, was 2.19 ± 0.38 mg/kg per dose (range 1.58-3.16). The time course of the plasma concentration of colistin is shown in Figure 1.
A wide interindividual variability was seen in all pharmacokinetic parameters. The maximum concentration of colistin occurred 1 h after beginning CMS infusion, confirming the previously reported relatively rapid conversion of CMS to colistin.1 At steady
Pharmacokinetics of Colistin
Information about the pharmacokinetics of colistin in critically ill patients is very limited.17, 18, 19 Moreover, the dose regimens commonly used until now are based on pharmacokinetic studies in which colistin was measured by microbiological assays that were not able to discriminate between CMS (inactive) and colistin (the active form). In this study conducted in critically ill patients with ventilator-associated pneumonia, we have investigated the steady-state plasma pharmacokinetics and the
Conclusions
In critically ill adult patients, the IV administration of CMS, 2 million International Units (174 mg) q8h, results in apparently suboptimal plasma concentration of colistin, which, moreover, was undetectable in BAL. However, because despite all these limits IV CMS has been successful in the treatment of multidrug-resistant gram-negative infections, and because colistin binds to tissues, the pharmacokinetic-pharmacodynamic relationship of this antibiotic should be investigated further.
Acknowledgments
Author contributions: Dr Imberti: contributed to study design, data analysis and interpretation, writing the manuscript, and providing final approval of the version submitted for publication.
Dr Cusato: contributed to study design, performing HPLC measurements, data analysis and interpretation, writing the manuscript, and providing final approval of the version submitted for publication.
Dr Villani: contributed to performing HPLC measurements, interpreting data, and providing final approval of
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2022, International Journal of Antimicrobial AgentsCitation Excerpt :Notably, in many cases colistin is the only available agent when tackling infections caused by carbapenemase-producing P. aeruginosa or A. baumannii [7]. There has been an increased interest in nebulised CMS for the treatment of VAP caused by XDR Gram-negative bacteria, considering that epithelial lining fluid (ELF) formed colistin concentrations are undetectable after IV CMS administration [5,8]. Nebulised CMS has the advantage of directly reaching the lung parenchyma by avoiding crossing membranes of the lung, with decreased systemic toxicity compared with IV administration [9,10].
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