Mechanisms of bacterial resistance to antimicrobial agents, with particular reference to cefotaxime and other beta-lactam compounds.

Abstract

Many mechanisms exist by which bacteria can become resistant to antimicrobial agents. Although mutational events are important in the development of resistance to some agents, by far the most important factor in resistance is extrachromosomal genetic material in the form of plasmids. Important mechanisms of bacterial resistance to antibiotics are interference with the transport of the antimicrobial agents into the bacterial cell, inactivation of the agent, and alteration of the target site or metabolic pathway by the microorganism. In order to affect bacteria, beta-lactam antibiotics must pass through proteins at the surface of the cell, must evade destruction by beta-lactamases, and must have an affinity for proteins involved in cell wall synthesis. A number of the new beta-lactam antibiotics, because of their great resistance to destruction by beta-lactamases and their high affinity for penicillin-binding proteins, have overcome many of the mechanisms bacteria have used in the past to resist beta-lactam drugs.