Steady-state pharmacokinetic and pharmacodynamic profiling of colistin in critically ill patients with multi-drug-resistant gram-negative bacterial infections, along with differences in clinical, microbiological and safety outcome

摘要

Limited data are present regarding the steady-state pharmacokinetics and pharmacodynamics of colistin in critically ill patients suffering from multi-drug-resistant gram-negative bacterial (MDR-GNB) infections. We aimed to profile the steady-state pharmacokinetics and pharmacodynamics of colistin in critically ill patients with MDR-GNB infections, along with determining the predictors that could influence the clinical, microbiological and safety outcome. We recruited 30 critically ill patients suffering from MDR-GNB infections in our prospective open-label study. Intravenous colistimethate sodium (CMS) 2 million IU was administered concurrently with inhalational CMS 1 million IU every 8 hours. Steady-state plasma colistin levels were measured. Logistic regression analysis was used to identify various predictors of clinical, microbiological and safety outcome. A large variability was observed in the steady-state colistin pharmacokinetic/pharmacodynamic parameters, along with the factors that influenced the clinical, microbiological and safety outcome. In conclusion, steady-state colistin pharmacokinetic and pharmacodynamic parameters observed in our study were largely consistent with those reported in previous studies. High acute physiology and chronic health evaluation II scores were associated with poor clinical outcome. Log-transformed colistin maximum concentration, area under the plasma concentration curve for 8 hours, apparent total body clearance and apparent volume of distribution were significantly associated with the safety outcome.