Tafenoquine exhibits broad spectrum antifungal activity at clinically relevant concentrations and decreases lung fungal burden in an invasive pulmonary model of .

BACKGROUND

Tafenoquine is active against a broad range of pathogens and accumulates extensively in the lung. We profiled the susceptibility of fungal pathogens to tafenoquine and

METHODS

Minimum inhibitory concentrations [MICs] of medically important fungal pathogens were determined using conventional assays. The daily maximum tolerated dose [MTD] of tafenoquine was determined in neutropenic mice and the effect of two doses of tafenoquine [MTD and 0.5xMTD] on survival and fungal burden were assessed in and lung infections models.

RESULTS

Mean MICS against panels of yeasts and dimorphic/filamentous fungi were 4.5 and 8.3 ug/mL. The MTD of tafenoquine was 5 mg/kg/day. Against [MIC 16 ug/mL], tafenoquine did not increase survival or decrease fungal burden. Against , [MIC 4 ug/mL], tafenoquine decreased lung fungal burden [by 0.5 logs,  < 0.05 at the MTD] in a dose-related manner. Survival in the high-dose [MTD] tafenoquine group was 30% whereas it was 0% in the vehicle group and in most legacy studies.

CONCLUSIONS

Tafenoquine exhibited broad spectrum activity against medically important yeasts and fungi and a dose-related antifungal effect in a lung infection model at clinically relevant doses.