Garcia-Effron Guillermo
Laboratorio de Micología y Diagnóstico Molecular, Cátedra de Parasitología y Micología, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, C.P. 3000 Santa Fe, Argentina.
Consejo Nacional de Investigaciones Científicas y Tecnológicas, C.P. 3000 Santa Fe, Argentina.
J Fungi (Basel). 2020 Nov 1;6(4):262. doi: 10.3390/jof6040262.
Rezafungin (formerly CD101) is a new β-glucan synthase inhibitor that is chemically related with anidulafungin. It is considered the first molecule of the new generation of long-acting echinocandins. It has several advantages over the already approved by the Food and Drug Administration (FDA) echinocandins as it has better tissue penetration, better pharmacokinetic/phamacodynamic (PK/PD) pharmacometrics, and a good safety profile. It is much more stable in solution than the older echinocandins, making it more flexible in terms of dosing, storage, and manufacturing. These properties would allow rezafungin to be administered once-weekly (intravenous) and to be potentially administered topically and subcutaneously. In addition, higher dose regimens were tested with no evidence of toxic effect. This will eventually prevent (or reduce) the selection of resistant strains. Rezafungin also has several similarities with older echinocandins as they share the same in vitro behavior (very similar Minimum Inhibitory Concentration required to inhibit the growth of 50% of the isolates (MIC) and half enzyme maximal inhibitory concentration 50% (IC)) and spectrum, the same target, and the same mechanisms of resistance. The selection of mutants occurred at similar frequency for rezafungin than for anidulafungin and caspofungin. In this review, rezafungin mechanism of action, target, mechanism of resistance, and in vitro data are described in a comparative manner with the already approved echinocandins.
瑞扎芬净（曾用名CD101）是一种新型β-葡聚糖合酶抑制剂，与阿尼芬净在化学结构上相关。它被认为是新一代长效棘白菌素的首个分子。与已获美国食品药品监督管理局（FDA）批准的棘白菌素相比，它具有多项优势，因为它具有更好的组织穿透力、更优的药代动力学/药效学（PK/PD）参数以及良好的安全性。它在溶液中的稳定性比旧款棘白菌素高得多，这使其在给药、储存和生产方面更具灵活性。这些特性将使瑞扎芬净能够每周一次（静脉注射）给药，并且有可能进行局部和皮下给药。此外，还测试了更高剂量方案，未发现毒性作用证据。这最终将防止（或减少）耐药菌株的产生。瑞扎芬净与旧款棘白菌素也有一些相似之处，因为它们具有相同的体外行为（抑制50%分离株生长所需的最低抑菌浓度（MIC）和半数酶最大抑制浓度50%（IC）非常相似）和抗菌谱、相同的靶点以及相同的耐药机制。瑞扎芬净产生突变体的频率与阿尼芬净和卡泊芬净相似。在本综述中，将瑞扎芬净的作用机制、靶点、耐药机制及体外数据与已获批准的棘白菌素进行了比较描述。
