Question 1 · Hard
A 66-year-old woman has received micafungin for 3 weeks for an infected pancreatic collection and now has fever again. Blood cultures grow a small yeast that forms no pseudohyphae on cornmeal agar, and MALDI-TOF identifies Nakaseomyces glabratus (Candida glabrata). Broth microdilution MICs (µg/mL) with CLSI breakpoints for this species: micafungin 0.5 (S ≤0.06, R ≥0.25); anidulafungin 1 (S ≤0.12, R ≥0.5); fluconazole 16 (susceptible-dose dependent ≤32, R ≥64); amphotericin B 1 (no breakpoint; epidemiological cut-off 2). The best interpretation is:
- AAmphotericin B resistant; echinocandins active
- BEchinocandin susceptible; fluconazole resistant
- CEchinocandin resistant, probably from an FKS mutation
- DAll agents susceptible; continue micafungin
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Answer: C · Echinocandin resistant, probably from an FKS mutation
Both echinocandin MICs are above their CLSI resistant breakpoints for N. glabratus, and the resistance emerged during prolonged micafungin therapy. In this species, echinocandin resistance is usually caused by hot-spot mutations in the FKS1 or FKS2 genes, which encode the drug target, beta-1,3-glucan synthase; sequencing can confirm them. N. glabratus has no 'susceptible' fluconazole category, so an MIC of 16 µg/mL is susceptible-dose dependent, and azole resistance often develops as well. The amphotericin B MIC is below the epidemiological cut-off, so it is the agent most likely to remain active. The result should be phoned, because the patient is failing current therapy.
- A: Amphotericin B 1 µg/mL is below the cut-off of 2, so no resistance is shown.
- B: Both echinocandin MICs exceed the resistant breakpoints, and fluconazole is only SDD.
- D: Micafungin 0.5 and anidulafungin 1 µg/mL are above the resistant breakpoints.