Abstract
Candida auris is an emerging multiresistant yeast against which amphotericin B (AMB) is still the first therapeutic choice in certain clinical situations (i.e., meningitis, endophthalmitis, and urinary tract infections). As data about the in vitro killing activity of AMB against C. auris clades are lacking, we determined MICs, minimum fungicidal concentrations (MFCs), and killing activity of AMB against 22 isolates representing the 4 major C. auris clades (South Asian n = 6; East Asian n = 4; South African n = 6, and South American n = 6). MIC values were ≤1 mg/L regardless of clades; MFC ranges were, 1–4 mg/L, 2–4 mg/L, 2 mg/L, and 2–8 mg/L for South Asian, East Asian, South African, and South American clades, respectively. AMB showed concentration-, clade-, and isolate-dependent killing activity. AMB was fungicidal at 1 mg/L against two of six, two of four, three of six, and one of six isolates from the South Asian, East Asian, South African, and South American clades, respectively. Widefield fluorescence microscopy showed cell number decreases at 1 mg/L AMB in cases of the South Asian, East Asian, and South African clades. These data draw attention to the weak killing activity of AMB against C. auris regardless of clades, even when MICs are low (≤1 mg/L). Thus, AMB efficacy is unpredictable in treatment of invasive C. auris infections.
Highlights
Previous studies have shown that C. auris clades differ from each other in their virulence in Galleria mellonella and neutropenic murine models [6,7,8]
C. auris is able to produce large aggregates both in vitro and in vivo, a phenomenon which may be associated with its excellent ability to survive in different environmental conditions including the presence of antifungal agents [6,7,8,9]
Regardless of methods and clades, MIC values were never higher than the tentative susceptibility breakpoint (1 mg/L) suggested by the Centers for Disease Control and Prevention (CDC) (Table 1) [14]
Summary
Candida auris is an opportunistic yeast that has emerged worldwide and causes superficial as well as life threatening infections among critically ill patients [1,2,3,4]. Echinocandins (anidulafungin, caspofungin, and micafungin) are the recommended drugs for the treatment of invasive C. auris infection in individuals aged two months and older [14]. In patients who are unresponsive to echinocandin therapy or who have persistent candidemia, as well as in children younger than the age of two months, switching to liposomal or traditional amphotericin B (AMB) is recommended as initial therapy. Echinocandins penetrate poorly into the central nervous system, the eye, and the urinary tract; in cases of meningitis, endophthalmitis, and urinary tract infections, AMB is still the first therapeutic choice [14,15,16,17]
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