Interplay between beta-lactamase activity, outer membrane and active efflux system

The resistance of a Gram-negative bacterial strain to penicillin is determined by the sensitivity of the essential penicillin-binding proteins (PBPs), the amount and properties of the produced beta-lactamase(s), the permeability of the outer membrane and the efficiency of the efflux systems. The interplay between the last three mechanisms is discussed with examples stressing the importance of one or several of them in clinical isolates. Mathematical models are presented. In the relatively simple case of Escherichia coli (in which the efflux systems are often negligible when compared to the beta-lactamase activity) the MICs can be predicted on the basis of these models. Similarly, correct MIC predictions could be made for an Enterobacter cloacae strain which overproduced a class C enzyme