A novel method for evaluating the outer membrane permeability to beta-lactamase-stable beta-lactam antibiotics

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