Some U.S. cases of Candida auris have shown resistance to every available class of antifungal drug — a situation the CDC calls pan-resistance. Because the Clinical and Laboratory Standards Institute (CLSI) has not yet defined breakpoints specific to C. auris, the CDC has established tentative thresholds based on expert opinion and on breakpoints set for closely related Candida species.
Illustration of C. auris. Credit: CDC
Why Standard Breakpoints Don't Yet Exist
Breakpoints tell clinicians whether a drug is likely to work against a given pathogen. For C. auris, no such officially validated thresholds exist. The CLSI has published antifungal susceptibility guidelines for yeasts in general, but the link between microbiologic breakpoints and actual patient outcomes for C. auris is still unknown. The figures below are a general guide, not definitive resistance cutoffs.
Tentative MIC Breakpoints by Drug Class
The following tables show the CDC's interim minimum inhibitory concentration (MIC) thresholds, in micrograms per milliliter (µg/mL), above which an isolate should be considered resistant.
Triazoles
| Drug | Tentative MIC Breakpoint (µg/mL) | Notes |
|---|---|---|
| Fluconazole | ≥32 | Modal MIC among isolates tested at CDC was ≥256; isolates at ≥32 carried a resistance mutation in the Erg11 gene, making response to fluconazole unlikely. |
| Voriconazole and other second-generation triazoles | N/A | Fluconazole susceptibility can be used as a surrogate, but fluconazole-resistant isolates may occasionally respond to other triazoles; decisions must be made case by case. |
Polyene
| Drug | Tentative MIC Breakpoint (µg/mL) | Notes |
|---|---|---|
| Amphotericin B | ≥2 | A mouse-model pharmacokinetic/pharmacodynamic analysis suggests the breakpoint should be 1 or 1.5 under standard dosing, similar to other Candida species. Isolates with an MIC of ≥2 should be considered resistant. When using Etest and a result of 1.5 is obtained, round up to 2. |
Echinocandins
| Drug | Tentative MIC Breakpoint (µg/mL) | Notes |
|---|---|---|
| Anidulafungin | ≥4 | Breakpoints based on the modal MIC distribution of approximately 100 isolates from diverse geographic locations. |
| Caspofungin | ≥2 | |
| Micafungin | ≥4 |
How Widespread Is Resistance?
In the United States, roughly 90% of C. auris isolates have been resistant to fluconazole, about 30% have been resistant to amphotericin B, and fewer than 2% have been resistant to echinocandins. These figures may include multiple isolates from the same individuals and may shift as more isolates are tested.
Resistance to all three drug classes — pan-resistance — has been found in some U.S. isolates and has been reported to the CDC from other countries as well.
A High MIC Doesn't Always Rule Out a Drug
An elevated MIC for a particular antifungal does not automatically mean that drug should be abandoned. If other antifungal options have already failed for a patient, a drug with a high MIC may still be considered. The IDSA guidelines provide the framework for how susceptibility testing should be performed and interpreted in practice.
Sources
This article is based on "Antifungal Susceptibility Testing for C. auris," published by the Centers for Disease Control and Prevention (CDC), a work of the United States government in the public domain.
Licence: CC0 1.0 (public domain) · Adapted from www.cdc.gov
1
0
0
0
Comments
