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阿奇霉素及其他大环内酯类抗生素的亚抑菌浓度对铜绿假单胞菌毒力因子的抑制作用

Inhibition of Pseudomonas aeruginosa virulence factors by subinhibitory concentrations of azithromycin and other macrolide antibiotics.

作者信息

Molinari G, Guzmán C A, Pesce A, Schito G C

机构信息

Institute of Microbiology, University of Genoa, Italy.

出版信息

J Antimicrob Chemother. 1993 May;31(5):681-8. doi: 10.1093/jac/31.5.681.

DOI:10.1093/jac/31.5.681
PMID:8392997
Abstract

The ability of three macrolide antibiotics (erythromycin, clarithromycin and azithromycin) to inhibit the expression of several pathogenicity traits of Pseudomonas aeruginosa at concentrations that do not affect the rate of growth of this microorganism was investigated. Sub-MICs of azithromycin manifested the broadest spectrum of action and strongly suppressed the synthesis of elastase, proteases, lecithinase and DNase. Clarithromycin and erythromycin were far less effective. Gelatinase was reduced almost to the same level by the three antibiotics, while haemolysins and lipase were only marginally affected. Loss of motility was a strain and drug-dependent event, but all the macrolides tested shared the ability to induce this effect. However, only azithromycin totally suppressed synthesis of pyocyanin in all isolates. These results indicate that newer macrolides and especially axithromycin are endowed with a remarkable ability to inhibit in vitro the expression of a number of physiological processes that are considered more essential than replication in the pathogenesis of P. aeruginosa. Since erythromycin sub-MICs have already been shown to exert beneficial effects in clinical practice, our data, pointing to a much higher potency of azithromycin, suggest its use in future studies.

摘要

研究了三种大环内酯类抗生素(红霉素、克拉霉素和阿奇霉素)在不影响铜绿假单胞菌生长速率的浓度下抑制该微生物几种致病性状表达的能力。阿奇霉素的亚抑菌浓度表现出最广泛的作用谱,并强烈抑制弹性蛋白酶、蛋白酶、卵磷脂酶和脱氧核糖核酸酶的合成。克拉霉素和红霉素的效果则差得多。三种抗生素使明胶酶减少到几乎相同的水平,而溶血素和脂肪酶仅受到轻微影响。运动能力丧失是菌株和药物依赖性事件,但所有测试的大环内酯类药物都具有诱导这种效应的能力。然而,只有阿奇霉素能完全抑制所有分离株中绿脓菌素的合成。这些结果表明,新型大环内酯类抗生素尤其是阿奇霉素具有显著的能力,能在体外抑制许多在铜绿假单胞菌发病机制中被认为比复制更重要的生理过程的表达。由于红霉素亚抑菌浓度已在临床实践中显示出有益效果,我们的数据表明阿奇霉素效力更高,建议在未来研究中使用。

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