Simulation Approach for Dosage Optimization of Colistimethate Sodium in Critically Ill South Indian Patients - A Pilot Study

Abstract

Rationale use of antibiotics has become a global need with the existence of only a handful of antibiotics and rapid emergence of the antibiotic resistant microbial strains over the past two decades. Management of infections in critically ill patientswith drug resistance is a major healthcare challenge and Colistin (Polymyxin E) is one such last-resort antibiotic that is extensively being utilised as a salvage therapy in these patients. The present study aimed to estimate the primary pharmacokinetic (PK) parametersofColistin from plasma concentrationsobtained from eight critically ill renal compromised patientsby the conventional two-stage approach and suchparameters were leveraged to simulate the plasma drug concentrations with Creatinine clearance (CrCl)as a covariate.Primary PK parameters (Clearance (CL) and Volume of Distribution (V)) were found to be 9.29 L/h and 13.92 L respectively.Further simulations for 90 subjects with three ranges of CrClrevealed a wide deviation from the target concentration of Colistin with peak and trough plasma concentrations(mg/L) 2.05±0.95, 3.07±1.18, 5.45±2.16 and 0.39±0.28, 0.98±0.52, 1.85±1.73 respectively in the three groups with declining CrCl. These findings reinforce the need to perform TDM and dose optimization of colistin in critically ill patients.