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两性霉素B脂质制剂与三唑类药物对人多形核白细胞的相互作用及其对接合菌的抗真菌活性

Interaction of amphotericin B lipid formulations and triazoles with human polymorphonuclear leucocytes for antifungal activity against Zygomycetes.

作者信息

Simitsopoulou Maria, Roilides Emmanuel, Maloukou Avgi, Gil-Lamaignere Cristina, Walsh Thomas J

机构信息

Laboratory of Infectious Diseases, Third Department of Pediatrics, Aristotle University, Hippokration Hospital, Thessaloniki, Greece.

出版信息

Mycoses. 2008 Mar;51(2):147-54. doi: 10.1111/j.1439-0507.2007.01457.x.

DOI:10.1111/j.1439-0507.2007.01457.x
PMID:18254752
Abstract

The frequency of zygomycosis has increased considerably over recent years mainly in immunocompromised and diabetic patients. Little is known about the effects of host innate immunity against different Zygomycetes especially under the influence of antifungal agents. The antifungal activity of human polymorphonuclear leucocytes (PMN) in combination with liposomal amphotericin B (LAMB), amphotericin B lipid complex (ABLC), voriconazole (VRC) and posaconazole (PSC) against Rhizopus oryzae and Rhizopus microsporus, frequently isolated Zygomycetes, were studied and compared with Absidia corymbifera, a less pathogenic Zygomycete. Antifungal activity was evaluated as per cent of hyphal damage using the XTT metabolic assay. While A. corymbifera was more susceptible to PMN than the other two Zygomycetes, R. microsporus appeared to be the most susceptible to combined effects of amphotericin B formulations and VRC with PMN. LAMB exhibited synergistic activity with PMN in inducing hyphal damage to R. microsporus but not to the other fungi. In contrast, ABLC exhibited synergistic or additive activity with PMN against all three fungi. Among triazoles, only VRC exhibited additive effect with PMN against R. microsporus. Lipid formulations of amphotericin B and particularly ABLC interact with PMN predominantly in inducing augmented hyphal damage to three different species of Zygomycetes.

摘要

近年来,接合菌病的发病率显著上升,主要见于免疫功能低下和糖尿病患者。关于宿主固有免疫对不同接合菌的影响,尤其是在抗真菌药物作用下的影响,人们了解甚少。研究了人多形核白细胞(PMN)与脂质体两性霉素B(LAMB)、两性霉素B脂质复合物(ABLC)、伏立康唑(VRC)和泊沙康唑(PSC)联合对常见分离的米根霉和少根根霉的抗真菌活性,并与致病性较低的伞枝犁头霉进行比较。使用XTT代谢分析法,以菌丝损伤百分比评估抗真菌活性。与其他两种接合菌相比,伞枝犁头霉对PMN更敏感,而少根根霉似乎对两性霉素B制剂和VRC与PMN的联合作用最敏感。LAMB与PMN联合对少根根霉具有协同诱导菌丝损伤的活性,但对其他真菌无此作用。相比之下,ABLC与PMN联合对所有三种真菌均表现出协同或相加活性。在三唑类药物中,只有VRC与PMN联合对少根根霉具有相加作用。两性霉素B的脂质制剂,尤其是ABLC,与PMN相互作用,主要表现为对三种不同接合菌诱导增强的菌丝损伤。

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