澳大利亚三级实验室检测奥洛氟米对 507 株丝状真菌（包括抗真菌药物耐药株）的体外活性：2020-2023 年。

In vitro activity of olorofim against 507 filamentous fungi including antifungal drug-resistant strains at a tertiary laboratory in Australia: 2020-2023.

机构信息

Clinical Mycology Reference Laboratory, Centre for Infectious Diseases and Microbiology Laboratory Services, Institute for Clinical Pathology and Medical Research-New South Wales Health Pathology, Westmead Hospital, Westmead, NSW, Australia.

Sydney Institute for Infectious Diseases, University of Sydney, Westmead Hospital, Westmead, NSW, Australia.

出版信息

J Antimicrob Chemother. 2024 Oct 1;79(10):2611-2621. doi: 10.1093/jac/dkae267.

DOI:10.1093/jac/dkae267

PMID:39105545

Abstract

BACKGROUND

New antifungal agents are required to mitigate against azole-resistant Aspergillus and drug-resistant non-Aspergillus moulds. The novel orotomide, olorofim (F2G, Manchester, UK), has potent fungicidal activity against Aspergillus including azole-resistant Aspergillus fumigatus, Lomentospora prolificans and Scedosporium spp. Development of olorofim-specific clinical breakpoints/epidemiological cut-off values requires reliable MIC data.

OBJECTIVES

Determine the in vitro activity of olorofim compared with standard antifungals against mould pathogens at an Australian hospital.

MATERIALS AND METHODS

Olorofim MICs were determined for 507 clinical mould isolates using the CLSI M38-A3 standard. MICs of amphotericin B, anidulafungin, posaconazole, voriconazole and isavuconazole were obtained using Sensititre™ YeastOne YO10 and AUSNMRCI panels (Thermo-Fisher Scientific).

RESULTS

A. fumigatus sensu stricto was the commonest species (33.3%) followed by L. prolificans (18.3%), Scedosporium (11.4%) and Fusarium (6%) species. Olorofim modal MICs were ≤0.25 mg/L (MIC90 0.25 mg/L) for all Aspergillus except Aspergillus Section Usti (1 mg/L); MICs for nine azole-resistant/non-wild-type A. fumigatus ranged from 0.008 to 0.125 mg/L. The MIC90 of olorofim for L. prolificans was 0.5 mg/L, 0.25-0.5 mg/L for Scedosporium spp. and 8 mg/L for the F. solani complex but with modal MICs of 0.25 and 0.008 mg/L for F. oxysporum and F. proliferatum complexes, respectively. For Verruconis gallopava (n = 10), the olorofim MIC90 was 0.06 mg/L (voriconazole MIC90 2 mg/L, isavuconazole MICs of 4->8 mg/L). Olorofim had little activity against other dematiaceous moulds including Exophiala species.

CONCLUSIONS

Olorofim was highly active against Aspergillus spp. including azole-resistant A. fumigatus, L. prolificans, Scedosporium spp. and some Fusarium species with the new finding of potent activity against V. gallopava.

摘要

背景

需要新型抗真菌药物来应对唑类耐药的曲霉菌和耐药的非曲霉菌属霉菌。新型的托罗米德（olorofim）（英国曼彻斯特的 F2G 公司）对包括唑类耐药烟曲霉、繁茂枝顶孢霉和枝顶孢属在内的曲霉菌具有很强的杀菌活性。开发olorofim 特定的临床折点/流行病学临界值需要可靠的 MIC 数据。

目的

在澳大利亚一家医院确定 olorofim 与标准抗真菌药物相比对霉菌病原体的体外活性。

材料和方法

使用 CLSI M38-A3 标准测定了 507 株临床霉菌分离株的 olorofim MIC。通过 Sensititre™YeastOne YO10 和 AUSNMRCI 板（Thermo-Fisher Scientific）获得两性霉素 B、阿尼芬净、泊沙康唑、伏立康唑和伊曲康唑的 MIC。

结果

严格意义上的烟曲霉是最常见的物种（33.3%），其次是繁茂枝顶孢霉（18.3%）、枝顶孢属（11.4%）和镰刀菌属（6%）。除了 Aspergillus Section Usti（1 mg/L）外，olorofim 的模式 MIC 均≤0.25 mg/L（MIC90 0.25 mg/L）；9 株唑类耐药/非野生型烟曲霉的 MIC 范围为 0.008 至 0.125 mg/L。olorofim 对繁茂枝顶孢霉的 MIC90 为 0.5 mg/L，对枝顶孢属的 MIC0.25-0.5 mg/L，对镰刀菌属复合种的 MIC8 mg/L，但对尖孢镰刀菌复合种和层出镰刀菌复合种的模式 MIC 分别为 0.25 和 0.008 mg/L。对于弯颈霉（n=10），olorofim 的 MIC90 为 0.06 mg/L（伏立康唑 MIC90 为 2 mg/L，伊曲康唑 MIC 为 4->8 mg/L）。olorofim 对其他暗色霉菌的活性较低，包括外瓶霉属。