Fungal Section, National Institute of Quality Control in Health, INCQS/Fiocruz, Rio de Janeiro, RJ.
Mycology Laboratory, Evandro Chagas National Institute of Infectious Diseases, INI/Fiocruz, Rio de Janeiro, RJ.
Med Mycol. 2019 Oct 1;57(7):864-873. doi: 10.1093/mmy/myy150.
Early diagnosis, efficient clinical support, and proper antifungal therapy are essential to reduce death and sequels caused by cryptococcosis. The emergence of resistance to the antifungal drugs commonly used for cryptococcosis treatment is an important issue of concern. Thus, the in vitro antifungal susceptibility of clinical strains from northern Brazil, including C. neoformans VNI (n = 62) and C. gattii VGII (n = 37), to amphotericin B (AMB), 5-flucytosine, fluconazole, voriconazole, and itraconazole was evaluated using the Etest and Vitek 2 systems and the standardized broth microdilution (CLSI-BMD) methodology. According to the CLSI-BMD, the most active in vitro azole was voriconazole (C. neoformans VNI modal MIC of 0.06 μg/ml and C. gattii VGII modal MIC of 0.25 μg/ml), and fluconazole was the least active (modal MIC of 4 μg/ml for both fungi). Modal MICs for amphotericin B were 1 μg/ml for both fungi. In general, good essential agreement (EA) values were observed between the methods. However, AMB presented the lowest EA between CLSI-BMD and Etest for C. neoformans VNI and C. gattii VGII (1.6% and 2.56%, respectively, P < .05 for both). Considering the proposed Cryptococcus spp. epidemiological cutoff values, more than 97% of the studied isolates were categorized as wild-type for the azoles. However, the high frequency of C. neoformans VNI isolates in the population described here that displayed non-wild-type susceptibility to AMB is noteworthy. Epidemiological surveillance of the antifungal resistance of cryptococcal strains is relevant due to the potential burden and the high lethality of cryptococcal meningitis in the Amazon region.
早期诊断、有效的临床支持和适当的抗真菌治疗对于降低隐球菌病导致的死亡和后遗症至关重要。抗真菌药物治疗隐球菌病的耐药性的出现是一个重要的关注问题。因此，评估了来自巴西北部的临床菌株（包括新型隐球菌 VNI（n=62）和格特隐球菌 VGII（n=37））对两性霉素 B（AMB）、5-氟胞嘧啶、氟康唑、伏立康唑和伊曲康唑的体外抗真菌敏感性，使用 Etest 和 Vitek 2 系统和标准化肉汤微量稀释（CLSI-BMD）方法。根据 CLSI-BMD，最有效的唑类药物是伏立康唑（新型隐球菌 VNI 的模式 MIC 为 0.06 μg/ml，格特隐球菌 VGII 的模式 MIC 为 0.25 μg/ml），氟康唑的活性最低（两种真菌的模式 MIC 均为 4 μg/ml）。两性霉素 B 的模式 MIC 均为 1 μg/ml。总体而言，两种方法之间观察到良好的基本一致（EA）值。然而，对于新型隐球菌 VNI 和格特隐球菌 VGII，AMB 在 CLSI-BMD 和 Etest 之间的 EA 最低（分别为 1.6%和 2.56%，两者均为 P<0.05）。考虑到提出的隐球菌属流行病学截止值，超过 97%的研究分离株被归类为唑类药物野生型。然而，这里描述的新型隐球菌 VNI 分离株对两性霉素 B 的非野生型敏感性频率较高，这值得关注。由于隐球菌性脑膜炎在亚马逊地区的潜在负担和高致死率，对隐球菌菌株的抗真菌耐药性进行流行病学监测是很重要的。
