Clinically relevant members of the
Scedosporium
/
Pseudallescheria
species complex and
Lomentospora prolificans
are generally resistant against currently available systemic antifungal agents
in vitro
and the infection due to these species is difficult to treat. We studied the
in vivo
efficacy of a new fungicidal agent olorofim (formerly F901318) against scedosporiosis and lomentosporiosis in neutropenic animals. Cyclophosphamide immunosuppressed CD-1 mice infected by
Scedosporium apiospermum
,
Pseudallescheria boydii
(
Scedosporium boydii
) and
Lomentospora prolificans
were treated by intraperitoneal administration of olorofim (15 mg/kg every 8 h for 9 days). The efficacy of olorofim treatment was assessed by the survival rate at 10 days post infection, levels of serum (1-3)-β-d-glucan (BG), histopathology, and fungal burden of kidneys 3 days post infection. Olorofim therapy significantly improved survival compared to the untreated controls; 80%, 100% and 100% of treated mice survived infection by
Scedosporium apiospermum
,
Pseudallescheria boydii
, and
Lomentospora prolificans,
respectively while less than 20% of the control mice (PBS-treated) survived at 10 days post infection. In the olorofim-treated neutropenic CD-1 mice infected with all three species, serum BG levels were significantly suppressed and fungal DNA detected in the target organs was significantly lower than controls. Furthermore, histopathology of kidneys revealed no or only few lesions with hyphal elements in the olorofim-treated mice, while numerous fungal hyphae were present in control mice. These results indicate olorofim to be a promising therapeutic agent for systemic scedosporiosis/lomentosporiosis, a devastating emerging fungal infection difficult to treat with currently available antifungals.
Molecular and Phenotypic Data Supporting Distinct Species Statuses for Scedosporium apiospermum and Pseudallescheria boydii and the Proposed New Species Scedosporium dehoogii