Candida auris Resistant to Azole Antifungals, Amphotericin B, and Echinocandins
March 1, 2020 3 minutes read
By Stan Deresinski, MD, FACP, FIDSA
Clinical Professor of Medicine, Stanford University
Dr. Deresinski reports no financial relationships relevant to this field of study.
SYNOPSIS: Infection with Candida auris resistant to azole antifungals, amphotericin B, and echinocandins was identified in three patients in New York. Resistance to echinocandins was first detected after the patients had received an echinocandin as treatment.
SOURCE: Ostrowsky B, Greenko J, Adams E, et al; C. auris Investigation Work Group. Candida auris isolates resistant to three classes of antifungal medications – New York, 2019. MMWR Morb Mortal Wkly Rep 2020;69:6-9.
Between 2016, when Candida auris was first identified in New York state, and June 28, 2019, 349 patients had clinical cultures positive for the organism, while an additional 452 were positive on screening swabs of skin or nares. Of the first 277 isolates, 276 (99.6%) were resistant to fluconazole and 170 (61.3%) were resistant to amphotericin B, while none were resistant to echinocandins. Testing of 331 subsequent isolates found that 330 (99.7%) and 210 (63.4%) were resistant to fluconazole and amphotericin B, respectively, while resistance to echinocandins has emerged, found to be present in 13 (3.9%). Testing of further isolates found three that were resistant to all three classes of antifungals.
The first two patients identified as being infected with pan-resistant C. auris were ventilator-dependent, had multiple comorbidities, and were residents of long-term care facilities. Fluconazole- and amphotericin-resistant isolates (blood, urine, and intravenous catheter tip in one; urine and tracheal aspirate in the other) were found to be echinocandin-resistant also after this class of agents was used for treatment. Both patients died, but the contribution of C. auris infection to these outcomes was uncertain.
A subsequent retrospective review identified a third patient with multiple comorbidities and prolonged acute care and long-term care with pan-resistant C. auris bloodstream infection. As with the other two cases, resistance to echinocandins only became apparent after treatment with one of this class of antifungals. All three cases were epidemiologically unrelated.
COMMENTARY
C. auris was first identified after its recovery from the ear canal of a patient in Japan in 2009 and now has been reported from five continents. Concern regarding this organism is the result of its resistance to several antifungal agents and its association with hospital infection outbreaks. The latter may be, at least in part, the result of its ability to persist in the environment and its resistance to some antiseptic agents.
New York is not a stranger to C. auris. Almost one-half of the 911 C. auris clinical cases reported to the Centers for Disease Control and Prevention as of October 2019 were from New York state and, as of June 28, 2019, 801 patients either infected or colonized by this organism had been identified. As described here, three of the 801 had infections that were due to pan-resistant strains. Although the strains initially were resistant to fluconazole and amphotericin B, in each case the emergence of resistance to echinocandins (making the strains pan-resistant) occurred only after treatment with an echinocandin.
Because of the frequent resistance to both azole antifungals and amphotericin B, echinocandins have been considered the treatment of choice most often. However, reduced susceptibility to this class of antifungals has become increasingly encountered and, in fact, isolates resistant to all three of these classes have been reported previously elsewhere in the world.
C. auris previously has been misidentified often as Candida haemulonii, to which it is related — as it is to Candida lusitaniae, an organism often resistant to amphotericin B. Like Saccharomyces and Candida glabrata, and in contrast to Candida albicans, C. auris is haploid, a feature that may make resistance more likely to develop since mutation is required in only a single DNA strand.
Infection with Candida auris resistant to azole antifungals, amphotericin B, and echinocandins was identified in three patients in New York. Resistance to echinocandins was first detected after the patients had received an echinocandin as treatment.
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