title: Posaconazole prophylaxis in experimental systemic zygomycosis.
abstract: Three isolates of zygomycetes belonging to two different genera (Rhizopus oryzae and Absidia corymbifera) were used to produce a systemic infection in neutropenic mice. On days -2 and -1 and at 2 h prior to infection, the mice received either posaconazole (POS) at doses ranging from 20 to 80 mg/kg of body weight/day or amphotericin B (AMB) at 1 mg/kg/day. Antifungal drug efficacy was assessed by determination of the prolongation of survival, determination of the percentage of infected organs (brain, lung, spleen, and kidney), and histological examination for the number of infection foci and their sizes in brain and kidney tissues. AMB significantly prolonged the survival of mice infected with all isolates. POS significantly prolonged the survival of mice infected with zygomycetes. Cultured organs from mice infected with R. oryzae were all positive, while treated mice challenged with A. corymbifera generally showed lower percentages of infected organs compared with the percentages for the controls. Zygomycete isolates established an active infection (the presence of hyphae) in the brains and the kidneys of all controls. In mice challenged with R. oryzae, both antifungal drugs were effective at reducing the number and the size of infection foci in the kidneys. Only AMB reduced the numbers, but not the sizes, of infection foci in the brain. Finally, both drugs significantly reduced the numbers and the sizes of infection foci in both tissues of mice infected with A. corymbifera. Our data suggest that prophylaxis with POS has some potential to prevent zygomycosis.
authors.affiliation: Istituto di Malattie Infettive e Medicina Pubblica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria, Ospedali Riuniti Umberto I-Lancisi-Salesi, Via Conca, Torrette, Ancona 60020, Italy. l.infettive@ao-umbertoprimo.marche.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Barchiesi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Spreghini
authors.forename: Alfredo
authors.initials: A
authors.lastname: Santinelli
authors.forename: Annette W
authors.initials: AW
authors.lastname: Fothergill
authors.forename: Eleonora
authors.initials: E
authors.lastname: Pisa
authors.forename: Daniele
authors.initials: D
authors.lastname: Giannini
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rinaldi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Scalise
mesh_terms: D020095:Absidia / Q000187:drug effects / Q000254:growth & development; D000666:Amphotericin B / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D019072:Antibiotic Prophylaxis / Q000379:methods*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D007668:Kidney / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D009091:Mucormycosis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D012233:Rhizopus / Q000187:drug effects / Q000254:growth & development; D013154:Spleen / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D013997:Time Factors; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole; D000666:Amphotericin B