Antibacterial in vitro activity of fourth generation cephalosporins

Cefpirome, cefepime and cefaclidine are distinguished by having a positively charged quaternary ammonium at carbon 3 of the dihydrothiazone ring. This confers the distinctive advantages of higher permeability across the outer membrane and low affinity for chromosomal cephalosporinases compared to the third generation cephalosporins which lack this quaternary ammonium moiety. These properties result in a marked advantage against resistant mutants of several species containing either derepressed class C chromosomal beta-lactamases or variant class A beta-lactamase. These unique properties have led to the suggestion that these compounds represent a "fourth generation" of cephalosporins.