A New Cephalosporin with a Dual Mode of Action

Abstract

A cephalosporin, (6R,7R)-7-[(2R)-2-hydroxy-2-phenylacetamido]-3-(pyrid-2-yl- N -oxide) thiomethylceph-3-em-4-carboxylic acid (MCO), that could lead to a novel approach to the problem of β-lactamase destruction is described. The compound is slightly more resistant to some β-lactamases than is cephalothin, but it is still hydrolyzed by many to a varying degree. Hydrolysis of the β-lactam bond of a cephalosporin releases the 3-substituent, which in MCO is itself an antibacterial agent, 2-mercaptopyridine- N -oxide. Thus, MCO has a dual mode of action, and bacteria that do not produce an effective amount of a β-lactamase are inhibited by the intact cephalosporin, whereas those that do hydrolyze it are inhibited by the released antibacterial compound.