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We evaluated the combined performance of itraconazole and voriconazole Etest® gradient concentration strips for the detection of Aspergillus fumigatus azole resistance associated with cyp51a mutations confirmed by gene sequencing. Among 118 A. fumigatus clinical isolates collected in a French center, 6 (5%) had azole resistance mutations, 5 of which were probably of environmental origin. Using recent method-dependent epidemiological cutoff values as thresholds, the combination's sensitivity and specificity were 100% [95% confidence interval 61–100] and 99% [95–100]. Our results support itraconazole and voriconazole Etest® combined use as a promising self-sufficient method for simple, efficient and reliable cyp51a -related azole-resistant A. fumigatus detection. [ABSTRACT FROM AUTHOR]

Systemic fungal infections are associated with high mortality rates despite adequate treatment. Moreover, acquired resistance to antifungals is increasing, which further complicates the therapeutic management. One strategy to overcome antifungal resistance is to use antifungal combinations. In vitro, several techniques are used to assess drug interactions, such as the broth microdilution checkerboard, agar-diffusion methods, and time-kill curves. Currently, the most widely used technique is the checkerboard method. The aim of all these techniques is to determine if the interaction between antifungal agents is synergistic, indifferent, or antagonistic. However, the interpretation of the results remains difficult. Several methods of analysis can be used, based on different theories. The most commonly used method is the calculation of the fractional inhibitory concentration index. Determination of the usefulness of combination treatments in patients needs well-conducted clinical trials, which are difficult. It is therefore important to study antifungal combinations in vivo, in experimental animal models of fungal infections. Although mammalian models have mostly been used, new alternative animal models in invertebrates look promising. To evaluate the antifungal efficacy, the most commonly used criteria are the mortality rate and the fungal load in the target organs. [ABSTRACT FROM AUTHOR]

Reference methods used to assess the drug susceptibilities of Aspergillus fumigatus isolates consisted of EUCAST and CLSI standardized broth microdilution techniques. Considering the increasing rate and the potential impact on the clinical outcome of azole resistance in A. fumigatus , more suitable techniques for routine testing are needed. The gradient concentration strip (GCS) method has been favorably evaluated for yeast testing. The aim of this study was to compare the CGS test with EUCAST broth microdilution for amphotericin B (AMB), posaconazole (PCZ), itraconazole (ITZ), voriconazole (VRZ), and isavuconazole (ISA). A total of 121 Aspergillus section Fumigati strains were collected, including 24 A. fumigatus sensu stricto strains that were resistant to at least one azole drug. MICs were determined using GCS and EUCAST methods. Essential agreement between the 2 methods was considered when MICs fell within ±1 dilution or ±2 dilutions of the 2-fold dilution scale. Categorical agreement was defined as the percentage of strains classified in the same category (susceptible, intermediate, or resistant) with both methods. Essential agreements with ±1 dilution and ±2 dilutions were 96.7, 93.4, 90.0, 89.3, and 95% and 100, 99.2, 100, 97.5, and 100% for AMB, PCZ, ITZ, VRZ, and ISA, respectively. Categorical agreements were 94.3, 86.1, 89.3, and 88.5% for AMB, PCZ, ITZ, and VRZ, respectively. Detection of resistance was missed with the GCS for one strain (4.1%) for PCZ and for 2 strains (8.3%) for ISA. Determination of ITZ MICs using the GCS allowed the detection of 91.7% of azole-resistant strains. The GCS test appears to be a valuable method for screening azole-resistant A. fumigatus clinical isolates., (Copyright © 2020 American Society for Microbiology.)

To evaluate the in vitro susceptibility of Fusarium to isavuconazole, 75 clinical isolates were identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry and then tested with a broth microdilution method (EUCAST) and the gradient concentration strip (GCS) technique. The activity of isavuconazole overall was shown to be limited, with an MIC 50  of >16 μg/ml, without significant differences between the species complexes. The categorical agreement between GCS and EUCAST was 97.4% to 100%, making the GCS as a valuable alternative., (Copyright © 2020 American Society for Microbiology.)