Abstract:
The efficacy of different echinocandins is assessed by evaluating the in vitro activity of a novel antifungal, rezafungin, against invasive fungal isolates in comparison with anidulafungin and caspofungin. Using the broth microdilution (BMD) method, the susceptibility of 1000 clinical Candida isolates (including 400 C. albicans, 200 C. glabrata, 200 C. parapsilosis, 150 C. tropicalis and 50 C. krusei) and 150 Aspergillus isolates (100 A. fumigatus and 50 A. flavus) from the Eastern China Invasive Fungi Infection Group (ECIFIG) was tested for the antifungals including anidulafungin, rezafungin, caspofungin and fluconazole. The echinocandins showed strong activity against C. albicans that was maintained against fluconazole-resistant isolates. The GM MIC (geometric mean minimum inhibitory concentration) value of rezafungin was found to be comparable to that of anidulafungin or caspofungin against the five tested common Candida species. C. tropicalis exhibited higher resistance rates (about 8.67-40.67% in different antifungals) than the other four Candida species. Through the sequencing of FKS genes, we searched for mutations in echinocandin-resistant C. tropicalis isolates and found that all displayed alterations in FKS1 S654P. The determined MEC (minimal effective concentration) values against A. fumigatus and A. flavus for rezafungin (0.116 μg/mL, 0.110 μg/mL) are comparable to those of caspofungin (0.122 μg/mL, 0.142 μg/mL) but higher than for anidulafungin (0.064 μg/mL, 0.059 μg/mL). Thus, the in vitro activity of rezafungin appears comparable to anidulafungin and caspofungin against most common Candida and Aspergillus species. Rezafungin showed higher susceptibility rates against C. glabrata. Rezafungin indicates its potent activity for potential clinical application.
摘要:
通过评估新型抗真菌药的体外活性来评估不同棘白菌素的功效,rezafungin,与Anidulafungin和caspofungin相比,针对侵袭性真菌分离株。使用肉汤微量稀释(BMD)方法,1000株临床念珠菌(包括400株白色念珠菌,200C.光滑,200℃。测试了来自中国东部侵袭性真菌感染组(ECIFIG)的150个热带曲霉和50个克氏曲霉)和150个曲霉分离物(100个烟曲霉和50个黄曲霉)的抗真菌药,包括anidulafungin,rezafungin,卡泊芬净和氟康唑.棘白菌素类对白色念珠菌显示出很强的活性,其对氟康唑抗性分离株保持不变。发现rezafungin的GMMIC(几何平均最小抑制浓度)值与Anidulafungin或卡泊芬净相对于五种测试的常见念珠菌的GMMIC值相当。与其他四种念珠菌相比,热带念珠菌表现出更高的耐药率(在不同的抗真菌药中约为8.67-40.67%)。通过对FKS基因的测序,我们搜索了对棘白菌素耐药的热带梭菌分离株的突变,发现所有的FKS1S654P都显示出改变。瑞扎芬净对烟曲霉和黄曲霉的MEC(最小有效浓度)值(0.116μg/mL,0.110μg/mL)与卡泊芬净(0.122μg/mL,0.142μg/mL),但高于anidulafungin(0.064μg/mL,0.059μg/mL)。因此,对最常见的念珠菌和曲霉属物种,rezafungin的体外活性似乎与anidulafungin和卡泊芬净相当。Rezafungin对光滑梭菌的敏感性较高。Rezafungin表明其潜在的临床应用的有效活性。