Ghannoum M A, Chen A, Buhari M, Chandra J, Mukherjee P K, Baxa D, Golembieski A, Vazquez J A
Center for Medical Mycology, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, OH 44106, USA.
Clin Microbiol Infect. 2009 Mar;15(3):274-9. doi: 10.1111/j.1469-0691.2008.02660.x. Epub 2009 Feb 5.
Recent studies suggest that differences in antifungal activity among echinocandins may exist. In this study, the activities of three echinocandins (anidulafungin, caspofungin, and micafungin) against Candida parapsilosis isolates from burn unit patients, healthcare workers and the hospital environment were determined. Additionally, the effect of these echinocandins on the cell morphology of caspofungin-susceptible and caspofungin-non-susceptible isolates was assessed using scanning electron microscopy (SEM). The C. parapsilosis isolates obtained from patients were susceptible to anidulafungin, but were less so to caspofungin and micafungin. Isolates obtained from healthcare workers or environmental sources were susceptible to all antifungals. SEM data demonstrated that although anidulafungin and caspofungin were equally active against a caspofungin-susceptible C. parapsilosis strain, they differed in their ability to damage a caspofungin-non-susceptible strain, for which lower concentrations of anidulafungin (1 mg/L) than of caspofungin (16 mg/L) were needed to induce cellular damage and distortion of the cellular morphology. To determine whether the difference in the antifungal susceptibility of C. parapsilosis isolates to anidulafungin as compared to the other two echinocandins could be due to different mutations in the FKS1 gene, the sequences of the 493-bp region of this gene associated with echinocandin resistance were compared. No differences in the corresponding amino acid sequences were observed, indicating that differences in activity between anidulafungin and the other echinocandins are not related to mutations in this region. The results of this study provide evidence that differences exist between the activities of anidulafungin and the other echinocandins.
近期研究表明，棘白菌素类药物之间可能存在抗真菌活性差异。在本研究中，测定了三种棘白菌素（阿尼芬净、卡泊芬净和米卡芬净）对烧伤病房患者、医护人员以及医院环境中分离出的近平滑念珠菌的活性。此外，使用扫描电子显微镜（SEM）评估了这些棘白菌素对卡泊芬净敏感和卡泊芬净不敏感菌株细胞形态的影响。从患者中分离出的近平滑念珠菌对阿尼芬净敏感，但对卡泊芬净和米卡芬净的敏感性较低。从医护人员或环境来源分离出的菌株对所有抗真菌药物均敏感。SEM数据表明，尽管阿尼芬净和卡泊芬净对卡泊芬净敏感的近平滑念珠菌菌株具有同等活性，但它们对卡泊芬净不敏感菌株的破坏能力有所不同，对于该菌株，诱导细胞损伤和细胞形态畸变所需的阿尼芬净浓度（1 mg/L）低于卡泊芬净（16 mg/L）。为了确定近平滑念珠菌菌株对阿尼芬净与其他两种棘白菌素的抗真菌敏感性差异是否可能归因于FKS1基因的不同突变，比较了该基因与棘白菌素耐药性相关的493 bp区域的序列。未观察到相应氨基酸序列的差异，这表明阿尼芬净与其他棘白菌素之间的活性差异与该区域的突变无关。本研究结果提供了证据，证明阿尼芬净与其他棘白菌素的活性之间存在差异。
