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Changing Trends of Commonly Used Intensive Care Unit Antibiotics Due to Differential Membrane Permeability in Resistant Escherichia coli Collected in EASE Programme

Manu Chaudhary and Anurag Payasi

In order to understand resistance pattern of Escherichia coli clinical isolates, the outer membrane permeability trend of different antibiotics was studied. The outer membrane permeability of Elores was compared with other commonly used intensive care unit (ICU) drugs being used in the treatment of various infections caused by resistant E. coli. A total of fifty three isolates collected under EASE programme from North Indian hospitals, fifteen extended spectrum β-lactamases (ESBL) positive clinical isolates of E. coli were included in the study. Michaelis constants (Km) and maximal rates of substrate hydrolysis (Vmax) were determined from Lineweaver-Burk plot. Permeability coefficient was determined using the method described by Zimmermann and Rosslet. Elores demonstrated the lowest Vmax/Km ratio further indicating its lower affinity (high Km 209.9 ± 17.4 μM) towards β-lactamase or more stability against β-lactamase enzyme. The other comparator drugs including penems, colistin, β-lactam and β-lactamase inhibitor combinations exhibited three to ten folds higher Vmax/Km ratio compared to Elores indicating very high affinity for β-lactamase induced degradation. Elores penetrated the outer membrane of ESBL producing resistant E. coli with permeability coefficient approximately 1.8, 2.2, 6.9, 2.5 and 2.3 times higher than imipenem plus cilastatin, meropenem, colistin, cefoperazone plus sulbactam, piperacillin plus tazobactam, respectively. The increased penetration of the Elores leads to higher periplasmic concentration of the drug resulting in reduced MIC. Our results clearly demonstrated that Elores exhibited the highest permeability coefficient, enhanced penetration, greater stability and periplasmic concentration leading to higher susceptibility towards resistant E. coli compared to other drugs. Therefore, Elores can be considered as an empiric drug of choice for the treatment of infections caused by E. coli positive with ESBL.