Objectives: CLSI M27-A3 has mostly been validated for determination of the MIC after 48 hours of incubation, except in the case of fluconazole (24h). The activity of Isavuconazole has mostly been determined against yeast isolates after 48h of incubation. Using the M27-A3 methodology, we studied the activity of Isavuconazole against Candida spp and other yeast isolates and determined the correlation between MICs after 24 and 48h.
Methods: A total of 297 recent clinical yeast blood isolates (n=193) or other clinical specimen sites (n=104) were studied: C albicans (n=82); C glabrata (n=67); C krusei (n=31); C parapsilosis (n=63); C tropicalis (n=17); Candida spp (n=7); and other yeast isolates (n=30). The antifungal activity of Isavuconazole was determined according to M27-A3. MIC (50% inhibition of growth) was read after 24h and 48h incubation. The MICs at 24h and 48h were considered to agree (essential agreement) when the value recorded after each incubation time was within +/-2 or fewer 2-fold dilutions of the other, considering 48h as the gold standard. In the absence of breakpoints for Isavuconazole, we chose voriconazole breakpoints (<=1 μg/mL, susceptible; 2 μg/mL susceptible–dose dependent; >=4 μg/mL, resistant) to evaluate the categorical agreement between MICs determined at 24h and 48h.
Results: MICs after 24h of incubation were not determined for 6/297 (2%) isolates (1 C krusei and 5 other) due to poor growth. Overall, the antifungal activity (in μg/mL) of Isavuconazole obtained after 24/48h of incubation was: MIC50 (<=0.015/0.031), MIC90 (0.125/0.25), and MIC range (<=0.015->16). Although the overall essential agreement between both procedures was 87.6% (Figure), inter-specific differences were noted with C parapsilosis and C tropicalis showing the highest agreement (100%) and C glabrata the lowest (67.2%). Strains were classified (after 24/48h of incubation) as susceptible (99%/97.9%), susceptible–dose dependent (0.3%/1.4%), and resistant (0.7%, C tropicalis). Categorical agreement was 98.9%, and only 3 strains (2 C glabrata and 1 C tropicalis) showed minor errors.
Conclusions: The antifungal activity of Isavuconazole against Candida and other yeasts can be obtained after 24 hours of incubation with no major or very major discrepancies. Validation of this procedure in future studies including a higher number of fluconazole/Isavuconazole-resistant isolates is warranted.
- ECCMID 20th (2010)