Murine Model of a Disseminated Infection by the Novel Fungus Fonsecaea monophora and Successful Treatment with Posaconazole

Abstract

The dematiaceous fungus Fonsecaea monophora is a causal agent of cerebral phaeohyphomycosis (10) and chromoblastomycosis (11-13). On the basis of molecular studies (3, 7), this fungus has recently been segregated from Fonsecaea pedrosoi, a traditionally well-known pathogen. Since very little is known about the pathogenicity and antifungal susceptibility of this novel fungus, the aim of this study was to develop a murine model of disseminated infection by F. monophora to evaluate its virulence and compare the therapeutic efficacies of amphotericin B (AMB), itraconazole (ITZ), and posaconazole (PSC).Two clinical strains of Fonsecaea monophora were used: CBS 269.37 and CBS 117236. Their in vitro antifungal susceptibility tests (8) showed MICs of 1 g/ml for AMB; 0.5 and 0.25

Antifungal Susceptibility Patterns of Opportunistic Fungi in the Genera Verruconis and Ochroconis

“…Based on the data presented in the current study, POS and echinocandins were the antimycotics with the best overall activity, having broad-spectrum activity against both thermotolerant and mesophilic species. The apparently good penetration of POS into the central nervous system (CNS), with the MIC falling well below the serum levels achievable with standard dosing regimens (38), combined with excellent in vitro data (39) and activity in animal models (40)(41)(42)(43), supports the use of POS for difficult-to-treat disseminated brain infections. In the clinical setting, POS has been used successfully in cases of cerebral and disseminated phaeohyphomycosis (44,45).…”

Melanized Fungi in Human Disease

“…In another murine model of C. bantiana infection, posaconazole and flucytosine improved survival alone, though the combination of posaconazole, flucytosine, and micafungin yielded the greatest benefit (481). In a recent murine model of F. monophora, posaconazole was associated with significantly better survival than amphotericin B or itraconazole (113). S. prolificans was studied in a murine model, and the combination of micafungin with either voriconazole or amphotericin B was associated with improved survival, though the triple combination of all three agents was not more effective (637).…”

“…F. pedrosoi is known almost exclusively as an agent of chromoblastomycosis (45,515,610,695), while the newly described F. monophora (Fig. 8) (113). Both species form conidia from swollen denticles which give rise to secondary and tertiary conidia in short chains of up to four conidia.…”

Tissue Penetration of Antifungal Agents

“…Thus, CSF concentrations in two patients with bacterial meningitis and cerebral fungal infection were 44% and 230%, respectively, of those in plasma (87). In mice infected with Cryptococcus gattii or Fonsecaea monophora, a bioassay revealed that brain tissue concentrations of posaconazole were approximately 53% of those in serum at daily doses of Յ20 mg/kg but increased to 70% to 80% at a daily dose of 40 mg/kg (88,89).…”