The evolution of resistance to cephalosporins.

The expression of resistance to cephalosporins is highly varied and due to various mechanisms. The greatest disadvantage of the cephalosporins is that they are inactivated by the array of beta-lactamases produced by bacteria. The high levels of chromosomal enzymes produced by these organisms are a major cause of cephalosporin resistance. Plasmid-mediated beta-lactamases (PMBLs) have also been implicated as causes of resistance, and other cephalosporinases have been described. Point mutations of specific amino acids of well-recognized PMBLs (e.g., TEM-1 and SHV-1) have also produced enzymes capable of attacking a wider spectrum of beta-lactam agents. The availability of newer beta-lactams may be conducive to the development of such beta-lactamases, in which chromosomal and newer plasmid derivatives that may or may not contain the AmpC gene are selected. The occurrence of such enzymes is likely to continue to increase.