title: Efficacy of oleylphosphocholine (OlPC) in vitro and in a mouse model of invasive aspergillosis.
abstract: Invasive aspergillosis (IA) has become increasingly common and is characterised by high morbidity and mortality. Upcoming resistance threatens treatment with azoles and highlights the continuous need for novel therapeutics. This laboratory study investigated the in vitro and in vivo potential of the alkylphospholipid oleylphosphocholine (OlPC) against Aspergillus. In vitro activities of OlPC, miltefosine, posaconazole and voriconazole were determined for Aspergillus fumigatus, A. niger, A. terreus and A. flavus. In vivo efficacy of OlPC was evaluated in a systemic A. fumigatus mouse model, adopting a short-term and long-term oral or intraperitoneal dosing regimen. OlPC showed good in vitro activity against A. fumigatus (IC50 = 1.04 μmol l(-1)). Intraperitoneal administration of 50 mg kg(-1) day(-1) OlPC significantly reduced the fungal organ burdens at 4 days post-infection (dpi). Although 5- and 10-day OlPC treatment improved survival, organ burdens were not affected at 10 and 15 dpi. While this study showed excellent in vitro activity of OlPC against Aspergillus spp., its therapeutic efficacy in an acute mouse model for IA was less convincing. Given the limited therapeutic options in the current antifungal market for invasive infections, OlPC activity should be assessed in a less stringent in vivo model, potentially in combination treatment with other already marketed antifungal drugs.
authors.affiliation: Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Paulussen
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Boulet
authors.forename: Tom
authors.initials: T
authors.lastname: Bosschaerts
authors.forename: Paul
authors.initials: P
authors.lastname: Cos
authors.forename: Anny
authors.initials: A
authors.lastname: Fortin
authors.forename: Louis
authors.initials: L
authors.lastname: Maes
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy* / Q000382:microbiology; D001230:Aspergillus / Q000187:drug effects*; D001232:Aspergillus fumigatus / Q000187:drug effects; D001393:Azoles / Q000627:therapeutic use; D004195:Disease Models, Animal; D051379:Mice; D008826:Microbial Sensitivity Tests; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use*; D014230:Triazoles / Q000494:pharmacology; D065819:Voriconazole / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D011743:Pyrimidines; D014230:Triazoles; D010767:Phosphorylcholine; C039128:miltefosine; C101425:posaconazole; D065819:Voriconazole
keywords: Aspergillus fumigatus; Oleylphosphocholine; in vitro susceptibility; mouse model