Candida auris is an emerging nosocomial pathogen that is resistant to Fluconazole and variably susceptible to other systemic drug classes. Treatment with echinocandins has been recommended based on MICs in the susceptible range, but supporting in vivo data is lacking.
We tested the MIC of C. auris strains (n=12) to fluconazole, voriconazole, posaconazole. anidulafungin, amphotericin B and flucytosine. Representative C. auris strains from Israel and South Africa, and a reference C. albicans strain, were analyzed using time-kill curve assays. Fungicidal activity was defined as reduction of ≥3 Log from baseline CFU/mL. Response to caspofungin treatment was assessed in BALB/c mice immunosuppressed with cyclophosphamide and inoculated with 7x107 C. auriscells by tail vein injection. Mice were treated from day +1 to day +7 with caspofungin (IP) at doses of 1 mg/kg or 5 mg/kg and compared to sham-treated controls. Survival was assessed daily. Kaplan Meier survival analyses was performed and treatment arms were compared using the log-rank test.
Drug susceptibility results (MIC50 and MIC90) were: fluconazole, 64 and 128 mg/L; voriconazole, 0.5 and 24 mg/L; posaconazole, 0.5 and 27 mg/L; anidulafungin, 0.03 and 0.06 mg/L; amphotericin B, 2 and 8 mg/L; flucytosine, 0.3 and 1 mg/L. Time-kill curve analyses showed log reduction from baseline CFU concentration of -3.0 to -2.8 for fluconazole (MIC x1), 5.6 to 6.1 for amphotericin B (MIC x4) and -0.4 to -0.9 for caspofungin (MIC x16), consistent with fungicidal activity of amphotericin B and weak fungistatic activity of caspofungin. In the mouse model, survival rate was similar with sham treatment (33%) and treatment with caspofungin 1 mg/kg/day (44%) and 5 mg/kg/day (22%), P=0.7.
Despite generally low MIC, caspofungin has only mild fungistatic activity on C. auris and no effect on survival in a mouse infection model. Amphotericin B has fungicidal activity against C. auris.
J. Berman, None
N. Korolker, None
A. Novikov, None