BACKGROUND: @entity5637 resistance in @entity54 species is rare. We examined if mutations in FKS1 would result in a complete loss of @entity5637 activity in vivo in an experimental model of @entity2381 . METHODS: Neutropenic @entity19 were infected with either an @entity5637 -susceptible @entity70173 ) or an @entity5637 -resistant A. fumigatus laboratory strain harbouring 'hot-spot' substitution in Fks1p (AF @entity25265 ). @entity19 then received daily treatment with either @entity25928 or @entity11794 at varying dosages (0.25-16 mg/kg/day) for 5 days and @entity54 lung fungal burden was assessed by quantitative real-time PCR. RESULTS: Both strains produced histological evidence of progressive @entity20585 , but AF @entity25265 was less virulent than @entity70173 , as evidenced by lower lung fungal burden and longer median survival time. At > 0.5 mg/kg/day, both @entity25928 and @entity11794 reduced the lung fungal burden in @entity1398 animals infected with @entity70173 , but had mixed efficacy against the resistant AF @entity25265 strain. For @entity11794 , the fungal burden was reduced only at doses <1 mg/kg/day. @entity25928 also modestly reduced AF @entity25265 lung fungal burden, but only at > 4 mg/kg/day. CONCLUSIONS: Despite a lack of appreciable antifungal activity in vitro, both @entity25928 and @entity11794 were still modestly effective in vivo against a laboratory-generated A. fumigatus mutant harbouring the @entity25265 mutation in Fks1p. This persistent activity, combined with impaired fitness of the isolate in vivo, could partially explain why microbiologically documented @entity5637 -resistance in @entity54 species remains a rare clinical occurrence.

Comparative in vivo dose-dependent activity of XXXX and @entity25928 against @entity5637 -susceptible and -resistant @entity54 .

@entity25928 :: ('MESH:C102786', 'Chemical') :: ['anidulafungin', 'Anidulafungin'] @entity19 :: ('10090', 'Species') :: ['mice', 'Mice'] @entity5637 :: ('CHEBI:57248', 'Chemical') :: ['Echinocandin', 'echinocandin'] @entity2381 :: ('MESH:D001228', 'Disease') :: ['aspergillosis'] @entity1398 :: ('MESH:D009503', 'Disease') :: ['neutropenic'] @entity54 :: ('746128', 'Species') :: ['Aspergillus'] @entity25265 :: ('p|SUB|S|678|P', 'ProteinMutation') :: ['Ser678Pro'] @entity70173 :: ('330879', 'Species') :: ['Aspergillus fumigatus (AF 293', 'AF 293'] @entity20585 :: ('MESH:D055744', 'Disease') :: ['invasive pulmonary aspergillosis'] @entity11794 :: ('MESH:C105417', 'Chemical') :: ['caspofungin']
@entity11794 :: (MESH:C105417,Chemical) :: ['caspofungin']
