Posaconazole Therapy of Disseminated Phaeohyphomycosis in a Murine Model

Graybill, John R.; Najvar, Laura K.; Johnson, Elizabeth; Bocanegra, Rosie; Loebenberg, David

doi:10.1128/aac.48.6.2288-2291.2004

Cited by 42 publications

(25 citation statements)

References 23 publications

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“…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).…”

Section: Discussionmentioning

confidence: 96%

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

Seyedmousavi

Samerpitak

Rijs

et al. 2014

Antimicrob Agents Chemother

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Section: Discussionmentioning

confidence: 96%

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

Seyedmousavi

Samerpitak

Rijs

et al. 2014

Antimicrob Agents Chemother

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“…Nevertheless, low MIC values of POS (Յ1 g/ml) and VRC (Յ2 g/ml) were recorded in 96% and 95% of isolates. Previously, Ben Ami et al reported that POS had low MICs against MF and is also effective in an animal model of PHM (2,29). Also, echinocandins had high MECs (Ն2 g/ml) in 39% of isolates, mainly among the genera Medicopsis, Exophiala, and Cladophialophora.…”

Section: Discussionmentioning

confidence: 96%

Molecular and Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry-Based Characterization of Clinically Significant Melanized Fungi in India

Singh

Kumar

et al. 2017

J Clin Microbiol

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Melanized or black fungi are a heterogeneous group of fungi causing cutaneous to systemic diseases with high mortality. These fungi are rarely reported as agents of human infections, primarily due to difficulties in their classical identification. In this study, we examined, using molecular methods and matrix-assisted laser desorption ioniazation-time of flight mass spectrometry (MALDI-TOF MS), the diversity of melanized fungi (MF) isolated from patients in 19 medical centers in India. Overall, during a 4-year period, 718 (5.3%) clinical specimens yielded MF. Of these, 72 (10%) isolates had clinical significance and were identified primarily by sequencing the internal transcribed spacer and large subunit (LSU) regions. MF represented 21 genera comprising 29 species, the majority of them belonging to the orders Pleosporales (50%) and Chaetothyriales (22%). Among the 29 fungal species identified in this study, only 6 (20%) species were identified by the MALDI-TOF MS due to the limited commercial database of Bruker Daltonics for MF. However, a 100% identification rate of 20 additional species identified in this study was obtained by constructing an inhouse database using 24-to 96-h-old liquid cultures. Further, the CLSI broth microdilution method revealed low MICs for posaconazole (Յ1 g/ml) and voriconazole (Յ2 g/ml) in 96% and 95% of isolates, respectively. Skin/subcutaneous and sinonasal and pulmonary phaeohyphomycosis due to MF were diagnosed in 21.4% (n ϭ 15) and 28.5% (n ϭ 20) of cases. Also, 10% of patients had central nervous system involvement (n ϭ 7), and 3 cases of fungal osteomyelitis due to Cladophialophora bantiana and Corynespora spp. were observed.

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“…Al-Abdely et al found posaconazole to be more effective than amphotericin B or itraconazole in murine models of central nervous system infection with R. mackenziei and C. bantiana (14,15). Posaconazole was also found to be effective in a model of disseminated E. dermatiditis infection (301). 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).…”

Section: Animal Models Of Infectionmentioning

confidence: 99%

Melanized Fungi in Human Disease

2010

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SUMMARY Melanized or dematiaceous fungi are associated with a wide variety of infectious syndromes. Many are soil organisms and are generally distributed worldwide, though certain species appear to have restricted geographic ranges. Though they are uncommon causes of disease, melanized fungi have been increasingly recognized as important pathogens, with most reports occurring in the past 20 years. The spectrum of diseases with which they are associated has also broadened and includes allergic disease, superficial and deep local infections, pneumonia, brain abscess, and disseminated infection. For some infections in immunocompetent individuals, such as allergic fungal sinusitis and brain abscess, they are among the most common etiologic fungi. Melanin is a likely virulence factor for these fungi. Diagnosis relies on careful microscopic and pathological examination, as well as clinical assessment of the patient, as these fungi are often considered contaminants. Therapy varies depending upon the clinical syndrome. Local infection may be cured with excision alone, while systemic disease is often refractory to therapy. Triazoles such as voriconazole, posaconazole, and itraconazole have the most consistent in vitro activity. Further studies are needed to better understand the pathogenesis and optimal treatment of these uncommon infections.

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Posaconazole Therapy of Disseminated Phaeohyphomycosis in a Murine Model

Cited by 42 publications

References 23 publications

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

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

Molecular and Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry-Based Characterization of Clinically Significant Melanized Fungi in India

Melanized Fungi in Human Disease

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