Interaction with CEP-1 beta-lactamase of RU 51746-2, the active form of the new oral cephalosporin RU 51807

Abstract

RU 51746-2 (which is the water soluble Na-salt of RU 51763) proved stable toward the most common beta-lactamases tested, with the sole exception of CEP-1, a plasmid-determined enzyme which is homologous to chromosomal beta-lactamases of some enterobacterial species. We studied the interaction of RU 51746-2 with CEP-1 in an E. coli C600 derivative containing pNU104, a multicopy plasmid in which an up-promoter mutation has increased the level of beta-lactamase expression. We found that RU 51746-2 was indeed hydrolyzed with slow, but significant, rates, which might account for the high minimum inhibitory concentration (MIC) values (> 128 microg/ml) we found for this laboratory strain. However, when the same test was performed with an 100-fold dilution of the sonic extract, in order to obtain enzyme levels comparable to those usually found in clinical isolates, no appreciable hydrolysis could be measured. This suggests that the slow hydrolysis of RU 51746-2 has no clinical meaning, since the activity of this drug is virtually unaffected by the amount of beta-lactamases usually found in wild strains.