In vitro evaluations of U-76,252 (CS-807): antimicrobial spectrum, beta-lactamase stability, and enzyme inhibition

Compound U-76,252 (Upjohn) is a cephalosporin ester that enhances oral absorption of the active free acid cephem, U-76,253. The active form structurally resembles parenteral aminothiazolyl-methoxyimino cephalosporins such as cefotaxime and its desacetyl metabolite. The g-negative antimicrobial activity of U-76,253 A (sodium salt of U-76,253) was most similar to that of cefixime and more potent than that of cefaclor or cefuroxime among the orally administered cephalosporins. Against g-positive bacteria, U-76,253 A was more active than cefixime. U-76,253 A was relatively stable to hydrolysis by five beta-lactamases (Type Ia, TEM-1, K1, CARB-2, and OXA-1), a stability most similar to cefotaxime and superior to that of cefaclor. Only the Type Ia (P99) enzyme was significantly inhibited by U-76,253 (IC 50 = 2.0 microM).