New possibilities for chromoblastomycosis and phaeohyphomycosis treatment: identification of two compounds from the MMV Pathogen Box® that present synergism with itraconazole.

BACKGROUND: Black fungi of the Herpotrichiellaceae family are agents of chromoblastomycosis and phaeohyphomycosis. There are few therapeutic options for these infections and it is common to associate antifungal drugs in their treatment. OBJECTIVES: To investigate the Medicines for Malaria Venture (MMV) Pathogen Box® for possible compounds presenting synergism with antifungal drugs used to treat black fungal infections. METHODS: An initial screening of the Pathogen Box® compounds was performed in combination with itraconazole or terbinafine at sub-inhibitory concentrations against Fonsecaea pedrosoi. Hits were further tested against eight Herpotrichiellaceae using the checkerboard method. FINDINGS: No synergism was observed with terbinafine. MMV687273 (SQ109) and MMV688415 showed synergism with itraconazole against F. pedrosoi. Synergism of these compounds was confirmed with some black fungi by the checkerboard method. SQ109 and itraconazole presented synergism for Exophiala dermatitidis, F. pedrosoi, F. monophora and F. nubica, with fungicidal activity for F. pedrosoi and F. monophora. MMV688415 presented synergism with itraconazole only for F. pedrosoi, with fungicidal activity. The synergic compounds had high selectivity index values when combined with itraconazole. MAIN CONCLUSIONS: These compounds in combination, particularly SQ109, are promising candidates to treat Fonsecaea spp. and E. dermatitidis infections, which account for most cases of chromoblastomycosis and phaeohyphomycosis.

[Sporotrichosis and dematiaceous fungal skin infections].

Sporotrichosis is a chronic infectious granuloma of skin. The detection of fungal elements in pathological examination and the isolation of Sporothrix schenckii from the lesion are requisite for diagnosis. The sporotrichin test is useful as an auxiliary examination, but a false-negative reaction might occur in some cases. Oral potassium iodide is first choice of treatment, because of its modest cost and usefulness, although gastrointestinal disorder is a frequent side effect. Itraconazole should be the second selection, and then terbinafine. Local thermotherapy is also effective as an additional therapy. Dematiaceous fungal skin infections are divided into two groups by their parasitic form, chromoblastomycosis and phaeohyphomycosis. Chromoblastomycosis is also called chromomycosis in Japan. It is most important for clinical diagnosis to detect dark brown spores in the scale of chromoblastomycosis and dark brown hyphae in the pus of phaeohyphomycosis by microscopic examination. Both morphological and molecular biological approaches are recommended for identification of fungi. In treatment, the drug appropriate in each case should be selected, and the combination of surgical excision, local thermotherapy, laser therapy or cryotherapy must be considered.

Caracterização fenotípica e genotípica de cepas de Fonsecaea pedrosoi isoladas de pacientes com cromoblastomicose / Phenotypic and genotypic characterization of Fonsecaea pedrosoi strains isolated from patients with chromoblastomycosis

A cromoblastomicose é uma infecção subcutânea causada por fungos demácios, como a Fonsecaea pedrosoi. O pleomorfismo e a similaridade entre gêneros e espécies, ocorrências características dessa classe de fungos, podem interferir na identificação morfológica. Vários esquemas terapêuticos para o tratamento da cromoblastomicose já foram utilizados, mas até o momento não existe uma terapia padrão. Em alguns casos, a correta identificação do agente etiológico pode auxiliar na indicação terapêutica, pois algumas espécies respondem melhor a determinados tratamentos do que outras. Com o objetivo de auxiliar o diagnóstico laboratorial da cromoblastomicose, foi desenvolvido um teste para identificação molecular e detecção rápida da Fonsecaea pedrosoi, empregando-se a metodologia da PCR-duplex com iniciadores específicos para a F. pedrosoi e universais para fungos...(AU)

A case of chromomycosis with tumor-like growth.

A 66-year-old woman who lived on Tokunoshima Island, a small and remote southern island of the Japanese archipelago, had suffered from chromomycosis for more than 30 years and presented with a tumor-like growth on the posterior crural region of his right leg. Fonsecaea pedrosoi was identified as the pathogen from its growth pattern and micromorphological characteristics. The patient was successfully treated with 5-fluorocytosine, itoraconazole, and topical thermotherapy.

[Chromomycosis in Iberia]. / Cromomicosis en Iberia

A 66 year old, Spaniard, born at Sueca (Valencia Province), was found infected with "Fonsecaea pedrosoi". His lesion, located in the inner aspect of the right arm, appeared when he was 7-8 years old, and progressed very slowly until he migrated to Venezuela, at 42. Thereafter it progressed more rapidly and started to hurt. Treatment included administration of 5-flucytosine at the daily dose of 150 mg./kg. during 4 and a half months and thermotherapy by means of a permanent adhesive tape on the lesion during 6 months. Eleven months after completion of the treatment, the patient is asymptomatic. This is the second case of chromomycosis originating in the Iberian peninsula. The importance of climate, clothing and age is discussed with reference to epidemiology of chromomycosis. The isolated strain of "F. pedrosoi" is the first one from the same region: its cultural characteristics and virulence among mice are studied and reported with some details. We think that in Europe, and especially in the Mediterranean countries, cases of chromomycosis did possibly occur, which were labelled as tuberculosis verrugosa or vegetans pyoderma owing to their histological picture.