A NOVEL METHOD FOR EVALUATING THE OUTER MEMBRANE PENETRABILITY OF β-LACTAMASESTABLE β-LACTAM ANTIBIOTICS

Abstract

A novel method is described which allows estimation of the outer membrane penetrability of β-lactamase-stable β-lactams by determining antibiotic concentrations in the periplasm. The method is based on measurement of the inhibiting activity of β-lactamase-stable β-lactams on the hydrolysis of a substrate by periplasmic β-lactamase. Application of the method to carbenicillin revealed that the high level of resistance to carbenicillin of an E. coli strain acquiring the plasmid encoding ampicillin resistance resulted from the poor ability of carbenicillin to penetrate the outer membrane of E. coli.