U-76,252（CS-807）的体外评估：抗菌谱、β-内酰胺酶稳定性及酶抑制作用

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

作者信息

Jones R N, Barry A L

机构信息

Clinical Microbiology Institute, Tualatin, OR 97062.

出版信息

Diagn Microbiol Infect Dis. 1987 Dec;8(4):245-9. doi: 10.1016/0732-8893(87)90056-3.

DOI:10.1016/0732-8893(87)90056-3

PMID:2856864

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).

摘要

化合物U - 76,252（由Upjohn公司生产）是一种头孢菌素酯，可增强活性游离酸头孢烯U - 76,253的口服吸收。其活性形式在结构上类似于肠外氨基噻唑基 - 甲氧基亚氨基头孢菌素，如头孢噻肟及其去乙酰代谢产物。在口服头孢菌素中，U - 76,253 A（U - 76,253的钠盐）对革兰氏阴性菌的抗菌活性与头孢克肟最为相似，且比头孢克洛或头孢呋辛更强。针对革兰氏阳性菌，U - 76,253 A比头孢克肟更具活性。U - 76,253 A对五种β - 内酰胺酶（Ia型、TEM - 1、K1、CARB - 2和OXA - 1）的水解作用相对稳定，这种稳定性与头孢噻肟最为相似，且优于头孢克洛。只有Ia型（P99）酶受到U - 76,253的显著抑制（IC50 = 2.0微摩尔）。