Maria Siopi, Sevasti Leventaki, Ioannis Pachoulis, Bram Spruijtenburg, Jacques F Meis, Spyros Pournaras, Georgia Vrioni, Athanasios Tsakris, Joseph Meletiadis
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The MTS-CLSI agreement was poor to weak for posaconazole (3%), itraconazole (20%), voriconazole (31%), and 5-flucytosine (37%), and moderate to strong for isavuconazole (58%), anidulafungin (68%), caspofungin (72%), micafungin (77%), and amphotericin B (85%). Most fluconazole MICs were off-scale, precluding a corresponding estimation. Significant interpretation discrepancies were recorded using the CDC's breakpoints for amphotericin B (66% CA, 34% major errors; MaEs), but not for fluconazole (98% CA, 1% MaEs, 1% very major errors; VmEs), anidulafungin (97% CA, 3% MaEs, 0% VmEs), micafungin (99% CA, 1% MaEs, 0% VmEs), and caspofungin (95% CA, 5% MaEs, 0% VmEs). Discrepancies were minimized using the amphotericin B method-specific WT-ULV of 4 mg/L (98% CA, 2% MaEs). The MTS-specific WT-ULVs of echinocandins could help to detect 100% of <i>FKS1</i> mutants. MTS generated higher MICs than the CLSI for azoles and 5-flucytosine. MTS could accurately detect fluconazole and echinocandin resistance among <i>C. auris</i> isolates. Nevertheless, it overestimated amphotericin B resistance as per the CDC's breakpoint of 2 mg/L. This can be improved by using the MTS-specific WT-ULV of 4 mg/L.IMPORTANCE<i>Candidozyma auris</i> (<i>Candida auris</i>) may exhibit resistance to multiple and sometimes even all currently available classes of antifungals. Hence, antifungal susceptibility testing (AFST) is of key importance to guide the clinician in therapeutic decision-making and to detect novel patterns of resistance. Gradient diffusion strips, referred to both Etest and MIC test strip (MTS), are broadly used in laboratory routine for AFST of yeasts. We therefore compared MTS with the reference Clinical and Laboratory Standards Institute (CLSI) broth microdilution method using an international panel of 100 <i>C</i>. <i>auris</i> isolates belonging to different clades. Significant interpretation discrepancies were recorded for amphotericin B (66% categorical agreement, 34% major errors), which could be minimized using the amphotericin B method-specific wild-type upper limit value of 4 mg/L. MTS generated higher MICs than the CLSI for azoles and 5-flucytosine. 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The agreement (±1 twofold dilution) between the methods and the categorical agreement (CA) based on the Centers for Disease Control and Prevention's (CDC's) tentative resistance breakpoints and MTS-specific wild-type upper limit values (WT-ULVs) were determined. The MTS-CLSI agreement was poor to weak for posaconazole (3%), itraconazole (20%), voriconazole (31%), and 5-flucytosine (37%), and moderate to strong for isavuconazole (58%), anidulafungin (68%), caspofungin (72%), micafungin (77%), and amphotericin B (85%). Most fluconazole MICs were off-scale, precluding a corresponding estimation. Significant interpretation discrepancies were recorded using the CDC's breakpoints for amphotericin B (66% CA, 34% major errors; MaEs), but not for fluconazole (98% CA, 1% MaEs, 1% very major errors; VmEs), anidulafungin (97% CA, 3% MaEs, 0% VmEs), micafungin (99% CA, 1% MaEs, 0% VmEs), and caspofungin (95% CA, 5% MaEs, 0% VmEs). Discrepancies were minimized using the amphotericin B method-specific WT-ULV of 4 mg/L (98% CA, 2% MaEs). The MTS-specific WT-ULVs of echinocandins could help to detect 100% of <i>FKS1</i> mutants. MTS generated higher MICs than the CLSI for azoles and 5-flucytosine. MTS could accurately detect fluconazole and echinocandin resistance among <i>C. auris</i> isolates. Nevertheless, it overestimated amphotericin B resistance as per the CDC's breakpoint of 2 mg/L. This can be improved by using the MTS-specific WT-ULV of 4 mg/L.IMPORTANCE<i>Candidozyma auris</i> (<i>Candida auris</i>) may exhibit resistance to multiple and sometimes even all currently available classes of antifungals. Hence, antifungal susceptibility testing (AFST) is of key importance to guide the clinician in therapeutic decision-making and to detect novel patterns of resistance. Gradient diffusion strips, referred to both Etest and MIC test strip (MTS), are broadly used in laboratory routine for AFST of yeasts. We therefore compared MTS with the reference Clinical and Laboratory Standards Institute (CLSI) broth microdilution method using an international panel of 100 <i>C</i>. <i>auris</i> isolates belonging to different clades. Significant interpretation discrepancies were recorded for amphotericin B (66% categorical agreement, 34% major errors), which could be minimized using the amphotericin B method-specific wild-type upper limit value of 4 mg/L. MTS generated higher MICs than the CLSI for azoles and 5-flucytosine. 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引用次数: 0
摘要
我们将MIC试纸条(MTS)与临床和实验室标准协会(CLSI)的参考肉汤微量稀释法进行了比较,使用了属于不同分支的100株耳念珠菌(耳念珠菌)的国际小组。确定方法与基于疾病控制与预防中心(CDC)暂定抗性断点和mts特异性野生型上限值(WT-ULVs)的分类一致(CA)之间的一致性(±1倍稀释)。泊沙康唑(3%)、伊曲康唑(20%)、伏立康唑(31%)和5-氟胞嘧啶(37%)的MTS-CLSI一致性较差至弱,而异戊康唑(58%)、阿尼杜拉芬金(68%)、卡泊芬金(72%)、米卡芬金(77%)和两性霉素B(85%)的MTS-CLSI一致性中等至强。大多数氟康唑的MICs都是非标准的,因此无法进行相应的估计。使用CDC的两性霉素B断点记录了显著的解释差异(66% CA, 34%主要错误;但氟康唑没有(98% CA, 1% MaEs, 1%非常严重错误;VmEs), anidulafungin (97% CA, 3% MaEs, 0% VmEs), micafungin (99% CA, 1% MaEs, 0% VmEs)和caspofungin (95% CA, 5% MaEs, 0% VmEs)。使用两性霉素B方法特异性WT-ULV为4 mg/L (98% CA, 2% MaEs)来最小化差异。棘白菌素的mts特异性WT-ULVs可以检测100%的FKS1突变体。MTS产生的mic高于唑类和5-氟胞嘧啶的CLSI。MTS能准确检测金黄色葡萄球菌对氟康唑和棘白菌素的耐药性。然而,它高估了两性霉素B耐药性,因为CDC的断点是2毫克/升。使用4 mg/L的mts特异性WT-ULV可以改善这一点。重要意义耳念珠菌可能对多种,有时甚至是所有目前可用的抗真菌药物具有耐药性。因此,抗真菌药敏试验(AFST)对指导临床医生的治疗决策和发现新的耐药模式至关重要。梯度扩散试纸条,即Etest和MIC试纸条(MTS),广泛用于酵母AFST的实验室常规检测。因此,我们将MTS与临床和实验室标准协会(CLSI)的参考肉汤微量稀释法进行了比较,使用了属于不同分支的100株金黄色葡萄球菌的国际小组。两性霉素B的解释差异显著(66%的分类一致,34%的主要错误),可以使用两性霉素B方法特异性野生型上限值4 mg/L来最小化。MTS产生的mic高于唑类和5-氟胞嘧啶的CLSI。MTS能准确检测氟康唑和棘白菌素耐药性。
Evaluation of the MIC test strips for antifungal susceptibility testing of Candidozyma auris (Candida auris) using a representative international collection of isolates.
We compared MIC test strips (MTS) with the reference Clinical and Laboratory Standards Institute (CLSI) broth microdilution method using an international panel of 100 Candidozyma auris (Candida auris) isolates belonging to different clades. The agreement (±1 twofold dilution) between the methods and the categorical agreement (CA) based on the Centers for Disease Control and Prevention's (CDC's) tentative resistance breakpoints and MTS-specific wild-type upper limit values (WT-ULVs) were determined. The MTS-CLSI agreement was poor to weak for posaconazole (3%), itraconazole (20%), voriconazole (31%), and 5-flucytosine (37%), and moderate to strong for isavuconazole (58%), anidulafungin (68%), caspofungin (72%), micafungin (77%), and amphotericin B (85%). Most fluconazole MICs were off-scale, precluding a corresponding estimation. Significant interpretation discrepancies were recorded using the CDC's breakpoints for amphotericin B (66% CA, 34% major errors; MaEs), but not for fluconazole (98% CA, 1% MaEs, 1% very major errors; VmEs), anidulafungin (97% CA, 3% MaEs, 0% VmEs), micafungin (99% CA, 1% MaEs, 0% VmEs), and caspofungin (95% CA, 5% MaEs, 0% VmEs). Discrepancies were minimized using the amphotericin B method-specific WT-ULV of 4 mg/L (98% CA, 2% MaEs). The MTS-specific WT-ULVs of echinocandins could help to detect 100% of FKS1 mutants. MTS generated higher MICs than the CLSI for azoles and 5-flucytosine. MTS could accurately detect fluconazole and echinocandin resistance among C. auris isolates. Nevertheless, it overestimated amphotericin B resistance as per the CDC's breakpoint of 2 mg/L. This can be improved by using the MTS-specific WT-ULV of 4 mg/L.IMPORTANCECandidozyma auris (Candida auris) may exhibit resistance to multiple and sometimes even all currently available classes of antifungals. Hence, antifungal susceptibility testing (AFST) is of key importance to guide the clinician in therapeutic decision-making and to detect novel patterns of resistance. Gradient diffusion strips, referred to both Etest and MIC test strip (MTS), are broadly used in laboratory routine for AFST of yeasts. We therefore compared MTS with the reference Clinical and Laboratory Standards Institute (CLSI) broth microdilution method using an international panel of 100 C. auris isolates belonging to different clades. Significant interpretation discrepancies were recorded for amphotericin B (66% categorical agreement, 34% major errors), which could be minimized using the amphotericin B method-specific wild-type upper limit value of 4 mg/L. MTS generated higher MICs than the CLSI for azoles and 5-flucytosine. MTS could accurately detect fluconazole and echinocandin resistance.
期刊介绍:
The Journal of Clinical Microbiology® disseminates the latest research concerning the laboratory diagnosis of human and animal infections, along with the laboratory's role in epidemiology and the management of infectious diseases.