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长效棘白菌素类药物雷扎芬净与其他抗真菌药物对当代侵袭性真菌分离株的活性检测(SENTRY 项目,2016 年至 2018 年)。

Activity of a Long-Acting Echinocandin, Rezafungin, and Comparator Antifungal Agents Tested against Contemporary Invasive Fungal Isolates (SENTRY Program, 2016 to 2018).

机构信息

JMI Laboratories, North Liberty, Iowa, USA.

University of Iowa, Iowa City, Iowa, USA.

出版信息

Antimicrob Agents Chemother. 2020 Mar 24;64(4). doi: 10.1128/AAC.00099-20.

Abstract

We evaluated the activity of rezafungin and comparators, using Clinical and Laboratory Standards Institute (CLSI) broth microdilution methods, against a worldwide collection of 2,205 invasive fungal isolates recovered from 2016 to 2018. ( = 1,904 isolates; 6 species), ( = 73), ( = 183), and ( = 45) isolates were tested for their susceptibility (S) to rezafungin as well as the comparators caspofungin, anidulafungin, micafungin, and azoles. Interpretive criteria were applied following CLSI published clinical breakpoints (CBPs) and epidemiological cutoff values (ECVs). Isolates displaying non-wild-type (non-WT) echinocandin MIC values were sequenced for hot spot (HS) mutations. Rezafungin inhibited 99.8% of isolates (MIC, 0.03/0.06 μg/ml), 95.7% of isolates (MIC, 0.06/0.12 μg/ml), 97.4% of isolates (MIC, 0.03/0.06 μg/ml), 100.0% of isolates (MIC, 0.03/0.06 μg/ml), and 100.0% of isolates (MIC, 0.06/0.12 μg/ml) at ≤0.12 μg/ml. All (329/329 [100.0%]) isolates (MIC,1/2 μg/ml) were inhibited by rezafungin at ≤4 μg/ml. Fluconazole resistance was detected among 8.6% of isolates, 12.5% of isolates, 3.2% of isolates, and 2.6% of isolates. The activity of rezafungin against these 6 spp. was similar to the activity of the other echinocandins. Detection of the HS mutation was performed by sequencing echinocandin-resistant or non-WT isolates. Good activity against was observed for fluconazole and the other azoles, whereas the echinocandins, including rezafungin, displayed limited activity. Rezafungin displayed activity similar to that of the other echinocandins against and These data contribute to accumulating research demonstrating the potential of rezafungin for preventing and treating invasive fungal infections.

摘要

我们使用临床和实验室标准协会(CLSI)肉汤微量稀释法,评估了雷沙康唑和对照药物对 2016 年至 2018 年期间从全球范围内分离的 2205 株侵袭性真菌的活性。研究包括(= 1904 株;6 种)、(= 73 株)、(= 183 株)和(= 45 株)分离株,对它们的敏感性(S)进行了雷沙康唑以及对照药物卡泊芬净、阿尼芬净、米卡芬净和唑类药物的测试。应用 CLSI 公布的临床折点(CBPs)和流行病学截断值(ECVs)进行解释。对显示非野生型(非-WT)棘白菌素 MIC 值的分离株进行热点(HS)突变测序。雷沙康唑抑制了 99.8%的(MIC,0.03/0.06μg/ml)、95.7%的(MIC,0.06/0.12μg/ml)、97.4%的(MIC,0.03/0.06μg/ml)、100.0%的(MIC,0.03/0.06μg/ml)和 100.0%的(MIC,0.06/0.12μg/ml)分离株(MIC,≤0.12μg/ml),MIC 值为 0.03/0.06μg/ml。所有(329/329 [100.0%])(MIC,1/2μg/ml)分离株在≤4μg/ml 时均被雷沙康唑抑制。(MIC,1/2μg/ml)分离株中有 8.6%、(MIC,0.12/0.25μg/ml)分离株中有 12.5%、(MIC,0.06/0.12μg/ml)分离株中有 3.2%和(MIC,0.03/0.06μg/ml)分离株中有 2.6%对氟康唑耐药。检测到 HS 突变是通过对棘白菌素耐药或非-WT 分离株进行测序。氟康唑和其他唑类药物对这些 6 种真菌表现出良好的活性,而包括雷沙康唑在内的棘白菌素类药物活性有限。雷沙康唑对和的活性与其他棘白菌素相似。氟康唑和其他唑类药物对表现出良好的活性,而包括雷沙康唑在内的棘白菌素类药物活性有限。雷沙康唑对和的活性与其他棘白菌素相似。这些数据有助于积累研究,证明雷沙康唑在预防和治疗侵袭性真菌感染方面的潜力。

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