Voriconazole is Less Effective than Other Triazoles for Treatment of Histoplasmosis

Background: Voriconazole is used to treat patients with histoplasmosis who are intolerant to itraconazole because of potential drug interactions. Hendrix reported higher mortality in patients treated with voriconazole than itraconazole raising the question if the Histoplasma isolates became less susceptible to voriconazole during treatment in those who failed treatment. Methods: Primary and failure isolates from a patient who failed treatment with fluconazole were incubated with increasing concentrations of voriconazole. Results: In vitro exposure of the patient’s primary isolate to voriconazole increased its MIC from 0.007 mcg/mL to 1.0 mcg/ mL (128-fold). Exposure of the failure isolate increased the MIC from 0.125 mcg/mL to 4 mcg/mL (32-fold). Exposure to voriconazole did not increase the MIC of the primary isolate to itracunazole but did increase the MIC of the failure isolate from 0.007 to 0.030 mcg/mL (4-fold). Conclusion: In vitro exposure Histoplasma capsulatum increased MICs to voriconazole 32 to 128-fold which could be a cause of treatment failure reported by Hendrix.