Isavuconazole is highly active in vitro against Candida species isolates but shows trailing effect

Abstract

Objective: Isavuconazole is a triazole previously shown to have potent in vitro activity against Aspergillus spp., Mucorales, and Candida spp. Unlike for other azoles, it is unclear if isavuconazole may induce a trailing effect. We studied isavuconazole MICs for a large collection of Candida isolates from blood samples and determined the extent of the trailing effect when using the EUCAST Edef 7.3.1 method. Methods: 761 molecularly identified Candida isolates from blood samples of 742 patients admitted to the hospital (January 2007 to September 2017) were evaluated and further tested for in vitro susceptibility to isavuconazole following the EUCAST E.Def 7.3.1 test method. Results: C. albicans showed the highest susceptibility, followed by C. parapsilosis and C. tropicalis (geometric mean MIC 0.003 vs 0.005/0.006, respectively; P < 0.001). In contrast, C. glabrata, and C. krusei had significantly higher MIC values (geometric mean MIC 0.094 vs 0.093, respectively). Isavuconazole MIC distributions were not truncated at the lowest concentration tested, except for C. albicans. Overall, the mean percentage of trailing was 12.9% but differences among species were observed: C. glabrata, C. albicans, and C. tropicalis exhibited higher trailing in comparison to C. parapsilosis and non-Candida yeasts (P < 0.001). The percentage of non-wild-type C. albicans (considering the heavy trailer isolates as wild-type), C. parapsilosis and C. glabrata isolates were 0.56% (2/355), 1.5% (3/200), and 4.65% (4/86), respectively. Conclusions: Isavuconazole showed high in vitro activity against Candida spp., particularly against C. albicans. Trailing effect is commonly observed with isavuconazole, particularly with C. glabrata.