The emergence of beta-lactam resistance among strains of Enterobacter cloacae and Pseudomonas aeruginosa.

The development of multiresistant bacterial strains associated with the use of the new beta-lactam antibiotic agents has prompted investigation into the mechanisms involved. Factors influencing beta-lactamase production, alterations of target-protein structure or production and decreases in bacterial outer membrane permeability have been identified as the three general mechanisms of beta-lactam resistance in aerobic Gram-negative bacteria. Because there is no DNA interaction by beta-lactam agents, emergence of resistance results from either spontaneous mutation or the presence of resistant subpopulations; the presence of antibiotics allows for overgrowth of resistant strains. Studies have indicated that there is a significant relationship between the rate of emerging resistance and the ratio of the minimum inhibitory concentration of a beta-lactam to the drug concentration used to select for resistance in vitro or achieved at the infection site in vivo. It is concluded that the use of synergistic combinations of agents should reduce the emergence of beta-lactam-resistant bacterial strains. Thus the choice of an appropriate therapeutic agent requires thorough evaluation of the specific pathogen for susceptibility to a variety of beta-lactam agents and aminoglycosides.