Abstract
Candida auris is an emerging and frequently multidrug-resistant pathogen against which the echinocandins are the preferred therapeutic option. We compared killing activities of anidulafungin, caspofungin, micafungin, and rezafungin against 13 isolates representing four C. auris clades (South Asian n = 3; East Asian n = 3; South African n = 3; South American n = 4, of which two were of environmental origin). Minimum inhibitory concentration MICs and killing kinetics in RPMI-1640 and RPMI-1640 plus 50% serum (50% serum) were determined. The four echinocandins were never fungicidal and induced large aggregates in RPMI-1640 and, less markedly, in 50% serum. Colony forming unit CFU decreases were found more consistently in 50% serum than in RPMI-1640. Isolates from the East Asian clade were killed at ≥1–≥ 4 mg/L with all echinocandins regardless of media. Anidulafungin and micafungin produced killing at peak drug serum concentration (8 mg/L) against environmental but not clinical isolates from the South American and the South African clades. Micafungin at ≥8 mg/L but not anidulafungin produced CFU decreases against the South Asian clade as well. In 50% serum, rezafungin at ≥1–≥ 8 mg/L produced killing against all four clades. The next generation echinocandin, rezafungin, showed the same or better activity at clinically attainable trough concentration regardless of media, compared with anidulafungin, caspofungin, and micafungin against all four tested C. auris clades.
Highlights
Candida auris is an emerging fungal pathogen causing asymptomatic yet ubiquitous colonization and life-threatening invasive infections among critically ill patients in intensive care units [1]
In 50% serum, Minimum inhibitory concentration (MIC) were higher with all four drugs, with the lowest range (0.25–1 mg/L) observed for rezafungin, which may be related to relatively lower protein binding [10,16]
MIC increases in serum were the lowest (1- to 8-fold) and highest (8- to 64-fold) with caspofungin and anidulafungin, respectively
Summary
Candida auris is an emerging fungal pathogen causing asymptomatic yet ubiquitous colonization and life-threatening invasive infections among critically ill patients in intensive care units [1]. C. auris lineages differ in their microscopic self-aggregating ability, growth in the presence of actidione, and ability to produce pseudomycelium on Dalmau cultures [4,5]; significant clade-specific differences in virulence between South Asian, East Asian, South African, and South American lineages were detected using invertebrate and neutropenic murine models [4,6,7]. This pathogen is almost always multidrug resistant, leaving. Echinocandin resistance is rare and is associated with mutations in FKS genes, which encode the catalytic subunit of β-1,3-D-glucan synthase [10]
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