Antifungal Susceptibility Testing and Interpretation

All Candida auris isolates should undergo antifungal susceptibility testing according to CLSI guidelines. Although C. auris is commonly multidrug resistant, levels of antifungal resistance can vary widely across isolates.

There are currently no established C. auris-specific susceptibility breakpoints. Therefore, breakpoints are defined based on those established for closely related Candida species and on expert opinion. Correlation between microbiologic breakpoints and clinical outcomes is not known at this time. For this reason, the information below should be considered as a general guide and not as definitive breakpoints for resistance. Please note that a finding of an elevated minimum inhibitory concentration (MIC) for an antifungal drug should not necessarily preclude its use, especially if the use of other antifungal drugs for the patient has been ineffective.

Triazoles Breakpoints for c. auris
Triazole
Class Drugs
Tentative MIC Breakpoints (µg/mL) Comment
Fluconazole ≥32 Modal minimum inhibitory concentration (MIC) to fluconazole among isolates tested at CDC was ≥256; isolates with MICs ≥32 were shown to have a resistance mutation in the Erg11 gene, making them unlikely to respond to fluconazole.
Voriconazole and other second generation triazoles N/A Consider using fluconazole susceptibility as a surrogate for second generation triazole susceptibility assessment. However, isolates that are resistant to fluconazole may respond to other triazoles occasionally. The decision to treat with another triazole will need to be made on case-by-case basis.

 

Polyenes Breakpoints for c. auris
Polyene Class Drug Tentative MIC Breakpoints (µg/mL) Comment
Amphotericin B ≥2 Recent pharmacokinetic/pharmacodynamic analysis of C. auris in a mouse model of infection indicates that under standard dosing, the breakpoint for amphotericin B should be 1 or 1.5, similar to what has been determined for other Candida species. Therefore, isolates with an MIC of ≥2 should now be considered resistant. If using Etest for amphotericin B and an MIC of 1.5 is determined, that value should be rounded up to 2.

 

Echinocandins Breakpoints for c. auris
Echinocandin Class Drugs Tentative MIC Breakpoints (µg/mL) Comment
Anidulafungin ≥ 4 Tentative breakpoints are based on the modal distribution of echinocandin MICs of approximately 100 isolates from diverse geographic locations.
Caspofungin ≥ 2
Micafungin ≥ 4

Based on these MIC breakpoints, many isolates are resistant to multiple classes of drugs. Some C. auris isolates have been found to be resistant to all three classes of antifungal drugs, including two CDC-confirmed cases in the United States. In both U.S. cases resistant to all antifungal drug classes, the isolates evolved pan-resistance in response to treatment.  We have received reports of pan-resistance found in other countries as well. In the United States, about 90% of C. auris isolates have been resistant to fluconazole, about 30% have been resistant to amphotericin B, and less than 5% have been resistant to echinocandins. These proportions may include multiple isolates from the same individuals and may change as more isolates are tested.