Caspofungin and Anidulafungin behave as a fungistatic agent against Candida auris

Abstract

Background: Candida auris is an emerging multiresistant nosocomial pathogen responsible for outbreaks around the world. It is associated with therapeutic failure and high mortality rates. Echinocandins are the empiric treatment choice for C. auris infections.However, clinical reports show that some patients respond poorly to this therapy. The aim of this study was to determine the in vitro activity of Caspofungin and Anidulafungin against C. auris by time-kill curves method. Methods & Materials: Twenty C. auris strains were studied. They were isolated from patients with proven invasive fungal infection. Susceptibility testing were performed following the Clinical and Laboratory Standards Institute (CLSI) M27-A3 and S4 documents. Time-killing experiments were conducted for 10 of the 20 isolates (in duplicate on 2 separate days) using RPMI-1640 buffered with MOPS. Caspofungin and anidulafungin tested concentration were 0.12, 0.25, 0.50, 1.00 and 8.00 μg/ml. The inoculum was adjusted to 1x105 CFU/ml using Neubauer chamber. A 0.05 ml aliquot of each dilution was taken at different time points (0, 2, 4, 6, 8, 10, 24 and 48 h). These aliquots were serially diluted in sterile water, spread onto Sabouraud plates and incubated at 35 °C to determine the numbers of CFU per milliliter. The killing kinetics and the fungicidal activity were analyzed by fitting the mean data at each time point to an exponential equation: Nt = N0 X e-kt (Nt viable yeasts at time t; N0 starting inoculum; K killing rate; t incubation time). Results: Anidulafungin and caspofungin geometric means were 1.68 μg/ml (range: 0.5-8.0 μg/ml) and 2.55 μg/ml (range 0.25-8.0 μg/mL), respectively. None of the drugs were able to reach fungicidal activity (no 99.9% inhibition). The mean time to reach 50% growth reduction were 5.30 ± 2.81 h and 1.74 ± 0.45 h for using the MIC values of each strain for anidulafungin and caspofungin, respectively. Conclusion: The tested echinocandins showed no in vitro fungicidal activity against C. auris at concentrations reached in serum despite straińs MICs. Caspofungin exhibited the highest time-kill rate