Wild-type MIC distributions and epidemiological cutoff values for 5-flucytosine and Candida species as determined by EUCAST broth microdilution.

IF 3.7 Q2 INFECTIOUS DISEASES JAC-Antimicrobial Resistance Pub Date : 2024-10-04 eCollection Date: 2024-10-01 DOI:10.1093/jacamr/dlae153
Fatima Zohra Delma, Willem J G Melchers, Paul E Verweij, Jochem B Buil
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Abstract

Objectives: EUCAST has established clinical breakpoints and epidemiological cutoff values (ECOFFs) for Candida spp. However, limited data are available for 5-flucytosine (5-FC). We assessed the in vitro susceptibility of 5-FC against a large collection of clinical Candida species using EUCAST methodology and determined the associated ECOFFs.

Methods: A total of 5622 Candida isolates were collected from patients across the Netherlands between 2008 and 2024. 5-FC MICs were determined using the EUCAST microbroth dilution reference method. Furthermore, MICs were extracted from the EUCAST website. The MICs from this study and those extracted were used to determine ECOFFs and local ECOFFs (L-ECOFFs).

Results: 5-FC exhibited potent in vitro activity against C. albicans, N. glabratus and C. parapsilosis, while decreased susceptibility was observed for C. tropicalis, Pichia species, K. marxianus, Y. lipolytica, and C. auris. The ECOFFs (mg/L) and the percentages of WT isolates for 5-FC were: C. albicans: 0.5 (97.2%), N. glabratus: 0.5 (96.6%), C. parapsilosis: 0.5 (99.5%) and P. kudriavzevii: 8 (99.4%). The L-ECOFF (mg/L) and the percentages of WT isolates for 5-FC were: C. dubliniensis: 0.25 (96.8%), C. tropicalis: 0.25 (67.2%), K. marxianus: 0.25 (48.0%), C. lusitaniae: 0.25 (86.5%), M. guillermondii: 0.125 (95.9%) and P. norvegiensis: 8 (94.2%).

Conclusions: 5-FC remains a valuable drug to manage difficult-to-treat invasive Candida infections. In vitro susceptibility cannot be predicted based on species identification for most Candida species, but requires MIC-testing. ECOFFs will help to interpret the MICs to support treatment decisions.

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欧盟肉汤微量稀释法测定的 5-氟胞嘧啶和念珠菌物种的野生型 MIC 分布和流行病学临界值。
目的:EUCAST 已经确定了念珠菌属的临床断点和流行病学截断值 (ECOFF),但 5-氟胞嘧啶 (5-FC) 的可用数据有限。我们采用 EUCAST 方法评估了 5-FC 对大量临床念珠菌的体外药敏性,并确定了相关的 ECOFF:方法:2008 年至 2024 年间,我们从荷兰各地的患者中收集了 5622 株念珠菌分离物。采用 EUCAST 微流稀释参考方法测定 5-FC MIC。此外,还从 EUCAST 网站上提取了 MICs。本研究中的 MICs 和提取的 MICs 被用于确定 ECOFFs 和局部 ECOFFs(L-ECOFFs):结果:5-FC 对白念球菌、N. glabratus 和 C. parapsilosis 具有很强的体外活性,而对 C. tropicalis、Pichia species、K. marxianus、Y. lipolytica 和 C. auris 的敏感性降低。5-FC 的 ECOFFs(毫克/升)和 WT 分离物的百分比分别为C. albicans: 0.5 (97.2%), N. glabratus:0.5(96.6%)、C. parapsilosis:0.5(99.5%)和 P. kudriavzevii:8(99.4%)。5-FC 的 L-ECOFF(毫克/升)和 WT 分离物的百分比分别为C. dubliniensis:0.25(96.8%),C. tropicalis:0.25(67.2%),P. kudriavzevii:8(99.4%):0.25(67.2%)、K. marxianus:0.25(48.0%)、C. lusitaniae:0.25(86.5%)、M. guillermondii:0.125(95.9%)和 P. norvegiensis:8(94.2%):5-FC仍是治疗难以治愈的侵袭性念珠菌感染的一种重要药物。体外药敏性不能根据大多数念珠菌的种类鉴定来预测,而需要进行 MIC 测试。ECOFFs 将有助于解释 MIC,为治疗决策提供支持。
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