Objectives: Candida auris is an emerging species causing disseminated candidiasis whit remarkable characteristics: difficult diagnosis and challenging treatment because multidrug-resistance. Isavuconazole, an extended-spectrum new triazole antifungal agent, was analyzed in vitro by a time-kill (TK) methodology to assess its activity against Candida auris.
Methods: In vitro static TK experiments and postantifungal-effect (PAFE) assays were performed as previously described (1) against three Candida auris clinical blood isolates from the outbreak of candidiasis at HUP La Fe (Valencia, Spain) (2). Concentrations assayed of isavuconazole (Basilea, UK) for both experiments were 0.06, 0.125, 0.25, 0.50 and 1 mg/l, based on MICs values previously determined by EUCAST E.def 7.3 method (3). For PAFE assays, cells were exposed to isavuconazole for 1 h. For both experiments, samples for viable count were taken at 0, 2, 4, 6, 8, 24 and 48 h. Plots of averaged colony counts (log10 CFU/ml) versus time were constructed and compared against a growth control (in absence of drug). The assays were performed in duplicate.
Results: None of the concentrations assayed in TK experiments showed fungicidal activity, even though a concentration-dependent reduction trend was observed when compared with control curve. As it could be expected from TK results, no PAFE effect was observed against any of the studied isolates. 
Conclusions: Despite the low MICs, isavuconazole did not show significant activity against the studied Candida auris isolates in the performed TK experiments. These results suggest that special care should be taken when interpreting the MIC values for resistant species such as Candida auris and other in vitro methodologies, like TK experiments, should also be considered for a more complete characterization of antimicrobial activity.
Funding: This study was partially financed by GIC15/78 IT-990-16 (Gobierno Vasco-Eusko Jaurlaritza), PI17/01538 (FIS, Spain) and SAF2017-86188-P (MINECO, Spain).
(1)	Gil-Alonso S et al. Postantifungal Effect of micafungin against the species complexes of Candida
albicans and Candida parapsilosis. PLoS ONE 2015; 10: e0132730.
(2)	Ruiz-Gaitán AC et al. Nosocomial fungemia by Candida auris: First four reported cases in continental Europe. Rev Iberoam Micol 2017;34:23.
(3)	K. Miranda-Cadena et al. In vitro activity of isavuconazole against fluconazole-resistant clinical isolates of Candida auris. Mycoses 2017;60 Suppl 2:66.


In vitro activity of Isavuconazole against Candida auris by time-kill and postantifungal-effect assays