Antimicrobial activity of Liposomal colistin against resistant E. coli in vitro and in vivo

Abstract

T his study was performed to investigate the liposome coated colistin for enhancing the oral pharmacokinetics, bioavailability, delivery and efficacy of the drug against resistant E. coli strain. Minimum inhibitory concentration (MIC) of colistin (C) and liposomal colistin (L) was 1.56 µg/ml and 0.00156 µg/ml for O125 sensitive colistin strain (CS and LS), while 100µg/ml and 0.025 µg/ml for O125 resistant strain (CR and LR). In vitro, time kill kinetics of liposomal colistin against sensitive and resistant O125 recorded 100% and 82.8% as a reduction% at 1 MIC, while ≥99.9% at 2 MIC for both strains after 1hr incubation time. The pharmacokinetic/ pharmacodynamics profiles were studied by single oral dose of colistin and liposomal colistin at 100000 IU/kg b.wt in healthy and diseased chicken. The pharmacokinetic parameters; Cmax/MIC ratio for CS and CR were 3.5 and 0.06. While, liposomal colistin recorded 3.9x10 3 and 247.2 for LS and LR, respectively. AUC/MIC ratios were 13.4, 0.248, 40.9x10 3 and 2.6x10 3 for CS, CR, LS and LR, respectively; proving the high efficacy of liposomal colistin with less significant activity of colistin. There was significant increment of t 1/2 Beta and MRT of liposomal colistin groups in comparison with colistin groups. Contraries, clearance Time (CL/F) was significantly decreased in liposomal colistin than colistin groups. Liposomal colistin en-hanced the bioavailability% from 5.2% to 49.2%. Liver E. coli count re-vealed highly significant decrease of LC for both strains nearly similar to negative control group after repeated treatment for 5 consecutive days; indicating the great effect by liposomal colistin on both E. coli strains especially for colistin resistant strain. This study recommends the liposomal colistin formulation against multidrug resistant E. coli infections.