title: In vitro evaluations of U-76,252 (CS-807): antimicrobial spectrum, beta-lactamase stability, and enzyme inhibition.
abstract: 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).
authors.affiliation: Clinical Microbiology Institute, Tualatin, OR 97062.
authors.forename: R N
authors.initials: RN
authors.lastname: Jones
authors.forename: A L
authors.initials: AL
authors.lastname: Barry
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D015296:Ceftizoxime / Q000031:analogs & derivatives*; D002511:Cephalosporins / Q000378:metabolism / Q000494:pharmacology*; D004341:Drug Evaluation; D004355:Drug Stability; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000494:pharmacology*; D000097627:Cefpodoxime Proxetil
chemical_list: D000900:Anti-Bacterial Agents; D015296:Ceftizoxime; D002511:Cephalosporins; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases; D000097627:Cefpodoxime Proxetil