Moxalactam: the first of a new class of beta-lactam antibiotics.

Abstract

Moxalactam is the first member of a new class of beta-lactam antibiotics to be evaluated clinically. Although structurally related to cephalosporins, moxalactam has an oxygen atom where the cephalosporin nucleus has a sulfur atom. The substitution of oxygen for sulfur in moxalactam provides it with greater antibacterial activity than that of its cephalosporin analog. Moxalactam has three other structural elements that affect biologic activity: the methyltetrazolethio moiety, which maximizes in vitro activity; the 7-alpha-methoxy substituent, which confers beta-lactamase stability; and the p-hydroxyphenylmalonyl group, which positively influences not only beta-lactamase stability and the antibacterial spectrum of moxalactam, but also its pharmacokinetics, and leads to a long half-life without high serum binding.