Interactions of formylamino- and methoxy-substituted beta-lactam antibiotics with beta-lactamases.

Cephem and nocardicin-type monocyclic beta-lactam antibiotics with a formylamino substituent were highly resistant to hydrolysis by both penicillinases and cephalosporinases. Among antibiotics with a methoxy substituent, an N-sulfonated monocyclic beta-lactam antibiotic, sulfazecin was resistant to beta-lactamases, but cephem antibiotics were sensitive to the cephalosporinase of Enterobacter cloacae. The resistance of the antibiotics to the beta-lactamases depended primarily on the presence of the substituent, but affinity for the beta-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 beta-lactamases as semisynthetic 7-methoxycephalosporins, but naturally occurring 7-methoxycephalosporins were poor inducers. The inducer activities of the antibiotics were not necessarily related to their beta-lactamase stabilities. The stabilities of the compounds to the beta-lactamases were well reflected in their antibacterial activities against beta-lactamase producing bacteria.