三唑类联合棘白菌素类抗真菌药物对曲霉的体外抑菌活性

In Vitro Antifungal Activity of Single or Combination of Triazole and Echinocandin against Aspergillus Species

目的观察三唑类联合棘白菌素类抗真菌药物对曲霉的体外抑菌活性。方法采用EUCAST方法检测62株曲霉对伏立康唑(VRC)、伊曲康唑(ICZ)、卡泊芬净(CAS)和米卡芬净(MICA)的体外敏感性,观察各药物的100%被抑菌最小浓度(MIC-0),VRC和ICZ的50%被抑菌最小浓度(MIC-2),以及CAS和MICA的最低有效浓度(MEC)。分别以MIC-0和MIC-2与MEC为观察终点,采用棋盘法检测VRC或ICZ联合CAS或MICA的分数抑菌浓度(FIC)。结果以MIC-0为终点的FIC,有2株烟曲霉对ICZ联合CAS或MICA表现为无关作用,其他烟曲霉株以及黄曲霉株和黑曲霉株对VRC或ICZ联合CAS或MICA均表现为协同作用;以MIC-2与MEC为终点的FIC,对VRC和CAS、VRC和MICA、ICZ和CAS以及ICZ和MICA的联合表现为协同作用的烟曲霉(n=35)分别有16株、21株、11株和14株,黄曲霉(n=20)分别有9株、13株、9株和11株,黑曲霉(n=7)分别有0株、2株、1株和1株。结论不同的观察终点,两药联合的敏感性结果差异较大,体外无法判断三唑类联合棘白菌素类抗真菌药物对曲霉抑菌活性的影响,需要在侵袭性曲霉病动物实验中进一步证实。

Objective To investigate antifungal activity in vitro of single or combination of triazole and echinocandin against Aspergillus species. Methods Based on EUCAST protocol, the susceptibilities of 62 isolates of Aspergillus spp. were determined for voriconazole （ VRC） , itraconazole （ ICZ） , caspofungin （ CAS） and micafungin （ MICA） . For VRC and ICZ, MIC-0 and MIC-2 were determined. For CAS and MICA,minimum effective concentration （ MEC） and MIC-2 were determined. The fractional inhibitory concentration （ FIC） was used to evaluate the effect of combination of triazole and echinocandin. Results Indifference was found in 2 isolates of Aspergillus fumigatus in combination of ICZ and CAS or MICA by using MIC-0 endpoint. Synergy was found in all other isolates of Aspergillus spp. With MIC-2 and MEC endpoints, synergy for VRC and CAS, VRC and MICA, ICZ and CAS and ICZ and MICA was found in 16,21, 11 and 14 isolates of Aspergillus fumigatus, 9, 13, 9 and 11 isolates of Aspergillus flavus, 0, 2, 1 and 1 isolates of Aspergillus niger, respectively. Conclusions The in vitro sensitivity results of combination of triazole and echinocandin are different with different endpoints. Thus, the efficacy of combination of triazole and echinocandin can not predicted by in vitro sensitivity and should be further confirmed in invasive aspergillosis animal experiments.