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3-取代头孢菌素E-1040对囊性纤维化痰液中病原体的体外活性

In vitro activity of E-1040, a 3-substituted cephalosporin, against pathogens from cystic fibrosis sputum.

作者信息

Stutman H R, Akaniro J C, Vidaurre C E, Marks M I

机构信息

Department of Pediatrics, Memorial Miller Children's Hospital, Long Beach, California 90801.

出版信息

Antimicrob Agents Chemother. 1990 Jul;34(7):1366-70. doi: 10.1128/AAC.34.7.1366.

DOI:10.1128/AAC.34.7.1366
PMID:2386368
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC175982/
Abstract

On the basis of preliminary in vitro data, we evaluated E-1040, a new cephalosporin, against 188 cystic fibrosis (CF) sputum isolates obtained from 26 CF centers in the United States. These isolates included mucoid and nonmucoid Pseudomonas aeruginosa, Pseudomonas cepacia, Staphylococcus aureus, Haemophilus influenzae, and Escherichia coli. In addition to MICs measured under standard conditions, selected isolates were tested at various pH values, inoculum sizes, and diluent (CF serum and sputum) conditions. E-1040 activities (MICs for 50 and 90% of the strains) against the isolates were as follows: P. aeruginosa (mucoid and nonmucoid), 1 and 4 micrograms/ml; P. cepacia, 4 and 16 micrograms/ml; S. aureus, 8 and 8 micrograms/ml; H. influenzae, 1 and 4 micrograms/ml; and E. coli, less than or equal to 0.12 and less than or equal to 0.12 microgram/ml. E-1040 activity against mucoid P. aeruginosa was 4-fold greater than that of aztreonam, 16-fold greater than that of ceftazidime, and 32-fold greater than that of piperacillin. E-1040 was similar to other broad-spectrum cephalosporins against S. aureus, H. influenzae, and E. coli. Bactericidal activity was less than or equal to 1 dilution of MIC for 88% of the strains, although kinetic studies with mucoid strains of P. aeruginosa demonstrated effective killing only at eight times the MIC. Variations in pH from 5 to 8, in inoculum size from 10(3) to 10(7) CFU/ml, and in diluent (CF serum or CF sputum) did not affect E-1040 activity.

摘要

基于初步的体外实验数据,我们对一种新型头孢菌素E - 1040进行了评估,该评估针对从美国26个囊性纤维化(CF)中心获取的188株CF痰液分离菌株展开。这些分离菌株包括黏液型和非黏液型铜绿假单胞菌、洋葱伯克霍尔德菌、金黄色葡萄球菌、流感嗜血杆菌以及大肠杆菌。除了在标准条件下测定的最低抑菌浓度(MIC)外,还对选定的分离菌株在不同pH值、接种量以及稀释剂(CF血清和痰液)条件下进行了测试。E - 1040对这些分离菌株的活性(50%和90%菌株的MIC)如下:铜绿假单胞菌(黏液型和非黏液型),1微克/毫升和4微克/毫升;洋葱伯克霍尔德菌,4微克/毫升和16微克/毫升;金黄色葡萄球菌,8微克/毫升和8微克/毫升;流感嗜血杆菌,1微克/毫升和4微克/毫升;大肠杆菌,小于或等于0.12微克/毫升和小于或等于0.12微克/毫升。E - 1040对黏液型铜绿假单胞菌的活性比对氨曲南高4倍,比对头孢他啶高16倍,比对哌拉西林高32倍。E - 1040对金黄色葡萄球菌、流感嗜血杆菌和大肠杆菌的活性与其他广谱头孢菌素相似。对于88%的菌株,杀菌活性小于或等于1倍MIC稀释度,尽管对黏液型铜绿假单胞菌菌株的动力学研究表明仅在8倍MIC时才有有效的杀菌作用。pH值从5到8、接种量从10³到10⁷CFU/毫升以及稀释剂(CF血清或CF痰液)的变化均不影响E - 1040的活性。

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