Antifungal Susceptibility and Phylogeny of Opportunistic Members of the Order Mucorales
Antifungal Susceptibility and Phylogeny of Opportunistic Members of the Order Mucorales
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DOI：
10.1128/jcm.06133-11
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发表时间：
2012-01-01
影响因子：
9.4
通讯作者：
Walther, Grit
中科院分区：
文献类型：
--
作者：
Vitale, Roxana G.;de Hoog, G. Sybren;Walther, Grit
测定了66株毛霉菌对8种抗真菌药物(两性霉素B、特比奈芬、伊曲康唑、泊沙康唑、伏立康唑、卡泊芬净、米卡芬净和5-氟胞嘧啶)的体外敏感性。根据核糖体大亚基重建了分子系统发育，以揭示分类单元特异性的敏感性图谱。毛霉目令人印象深刻的系统发育多样性反映在科、属和种水平上的易感性不同。两性霉素B是最有效的药物，但对根霉和坎宁安汉堡菌的作用较弱。泊沙康唑是第二有效的抗真菌药物，但对毛霉菌和克宁汉姆氏菌的活性降低，而伏立康唑对大多数菌株缺乏体外活性。属于毛霉科的属对泊沙康唑、伊曲康唑和特比奈芬有广泛的最低抑菌浓度，并包括耐药菌株。Cunninghamella也包含对所有测试的唑类药物耐药的菌株，但对特比奈芬完全敏感。相比之下，地钱科完全缺乏对这些抗真菌药物敏感性降低的菌株。合头星菌与地钱科植物的感病谱相似。毛霉对唑类的抗性高于根霉。只有根霉和卷叶毛霉对特比奈芬有种特异性反应。观察到对5-氟胞嘧啶、卡泊芬净和米卡芬净的完全或巨大耐药性。在所有测试属中都发现了体外敏感性的种内变异，但在毛霉和根霉中对唑类和特比奈芬的敏感性特别高。准确的病原体分子鉴定是预测治疗结果的必要条件。对于关键属的物种，如毛霉和根霉，表现出较高的种内变异，建议在开始治疗之前进行药敏测试。
The in vitro susceptibilities of 66 molecularly identified strains of the Mucorales to eight antifungals (amphotericin B, terbinafine, itraconazole, posaconazole, voriconazole, caspofungin, micafungin, and 5-fluorocytosine) were tested. Molecular phylogeny was reconstructed based on the nuclear ribosomal large subunit to reveal taxon-specific susceptibility profiles. The impressive phylogenetic diversity of the Mucorales was reflected in susceptibilities differing at family, genus, and species levels. Amphotericin B was the most active drug, though somewhat less against Rhizopus and Cunninghamella species. Posaconazole was the second most effective antifungal agent but showed reduced activity in Mucor and Cunninghamella strains, while voriconazole lacked in vitro activity for most strains. Genera attributed to the Mucoraceae exhibited a wide range of MICs for posaconazole, itraconazole, and terbinafine and included resistant strains. Cunninghamella also comprised strains resistant to all azoles tested but was fully susceptible to terbinafine. In contrast, the Lichtheimiaceae completely lacked strains with reduced susceptibility for these antifungals. Syncephalastrum species exhibited susceptibility profiles similar to those of the Lichtheimiaceae. Mucor species were more resistant to azoles than Rhizopus species. Species-specific responses were obtained for terbinafine where only Rhizopus arrhizus and Mucor circinelloides were resistant. Complete or vast resistance was observed for 5-fluorocytosine, caspofungin, and micafungin. Intraspecific variability of in vitro susceptibility was found in all genera tested but was especially high in Mucor and Rhizopus for azoles and terbinafine. Accurate molecular identification of etiologic agents is compulsory to predict therapy outcome. For species of critical genera such as Mucor and Rhizopus, exhibiting high intraspecific variation, susceptibility testing before the onset of therapy is recommended.