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 β-lactamases produced by bacteria. The high levels of chromosomal enzymes produced by these organisms are a major cause of cephalosporin resistance. Plasmid-mediated β-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 β-lactam agents. The availability of newer β-lactams may be conducive to the development of such β-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.