Interactions of formylamino— and methoxy-substituted β-lactam antibiotics with β-lactamases

Abstract

Cephem and nocardicin-type monocyclic, β-lactam antibiotics with aformylamino substituent were highly resistant to hydrolysis by both penicillinases and cephalosporinases. Among antibiotics with a methoxy substituent, an β-sulfonated monocyclic β-lactam antibiotic, sulfazecin was resistant to β-lactamases, but cephem antibiotics were sensitive to the cephalosporinase of Enterobacter cloacae. The resistance of the antibiotics to the β-lactamases depended primarily on the presence of the substituent, but affinity for the β-lactamases was affected not only by the substituent but also by the presence of other side chains. Formylamino compounds and sulfazecin were as good inducers of β-lactamases as semisynthetic 7-methoxycephalosporins, but naturally occurring 7-methoxycephalosporins were poor inducers. The inducer activities of the antibioticswere not necessarily related to their β-lactamase stabilities. The stabilities of the compounds to the β-lactamases were well reflected in their antibacterial activities against β-lactamase producing bacteria. © 1985, JAPAN ANTIBIOTICS RESEARCH ASSOCIATION. All rights reserved.