Mechanisms of resistance to beta-lactam antibiotics in strains of Staphylococcus aureus.

There are three major mechanisms of resistance of Staphylococcus aureus to beta-lactam antibiotics: enzyme mediated (penicillinase or beta-lactamase) by which the antibiotic is inactivated; intrinsic, which is not due to drug inactivation, and accounts for methicillin-resistance; and tolerance, in which there is a dissociation of the inhibitory and killing actions of beta-lactam antibiotics. In enzyme-mediated resistance, there are at least three different staphylococcal beta-lactamases, which probably account for differences in the inoculum effect with different cephalosporins. The intrinsic resistance is associated with differences in the affinity of beta-lactams for penicillin-binding proteins, but intrinsic resistance is probably more complex, because the pH of the medium, chelating agents, visible light, and temperature also effect its expression. Tolerance is clearly due to decreased autolytic enzyme activity (reflecting persistence of an enzyme inhibitor) of those tolerant organisms that need 32 (or more) times as much antibiotic for a bactericidal effect as for simple inhibition.