An 11-year-old neutered male domestic longhair cat was diagnosed with
histoplasmosis from fine-needle aspirates of an abdominal lymph node. Lymph node size initially decreased with
fluconazole therapy (11.8 mg/kg PO q12h); however, after 13 months of continuous
fluconazole therapy, lymphadenomegaly worsened and samples were collected for culture and antifungal susceptibility. The Histoplasma capsulatum isolate had a very high
fluconazole minimum inhibitory concentration (MIC) of 64 µg/ml and an
itraconazole MIC of 0.06 µg/ml. The owner declined a change to
itraconazole and, ultimately, the cat developed
neurologic signs and was euthanized. Owing to the initial response to
fluconazole followed by treatment failure and high MIC value, acquired
fluconazole resistance was suspected. Clinical breakpoints for
fluconazole for the dimorphic fungi are not available to define true antifungal resistance.
RELEVANCE AND NOVEL INFORMATION: This is the first published report of reduced susceptibility to
fluconazole in a cat being treated for
histoplasmosis.
Fluconazole failure and increases in MIC between pretreatment and long-term treatment isolates are known to occur in humans with
histoplasmosis. Practitioners should be aware of this possibility when treating cats with
fluconazole (particularly in cases with long-term [>1 year]
fluconazole therapy or in cases with disease recrudescence).