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PubMed1998

In vitro testing of susceptibilities of filamentous ascomycetes to voriconazole, itraconazole, and amphotericin B, with consideration of phylogenetic implications.

The in vitro susceptibilities of three hundred eighty-one isolates representing two classes, five orders, nine families, 30 genera, and 51 species of ascomycetous fungi to voriconazole, itraconazole, and amphotericin B were tested by using a modification of the National Committee for Clinical Laboratory Standards M27-A reference method. For those fungi of known phylogenetic relatedness, drug MICs were consistently low for isolates among all clades, except for members of the family Microascaceae. The highest MICs of all drugs tested were consistently for the Microascaceae, supporting the observation of fungal phylogeny and corresponding susceptibility to antifungal drugs. Itraconazole and voriconazole have a broad range of activity against phylogenetically similar agents of hyalohyphomycosis, phaeohyphomycosis, chromoblastomycosis, and mycetoma.

Amphotericin B↗

PubMedDate not supplied

In vitro susceptibility testing of Fonsecaea pedrosoi to antifungals.

Based on the difficulties experienced in the treatment of chromoblastomycosis, 12 primary human isolates of F. pedrosoi, were tested for their in vitro susceptibility to various antimycotics. We adapted the recommendations of the NCCLS for yeasts and followed the indications for mold testing from other authors in order to determine their MIC's and the MLC's. It was found that a significant proportion of the isolates were resistant to 3 of the 4 antimycotics tested, as revealed by high MIC values, as follows: 33% were resistant to amphotericin B (AMB), 58.3% to 5 fluocytosine (5 FC) and 66.7% to fluconazole (FLU). Contrarywise, none of the isolates proved resistant to itraconazole (ITZ). Determination of the MLC's revealed that a larger proportion of the isolates were not killed by AMB, 5 FC (91.7%), FLU (100%) or even, ITZ (41.7%). These data indicate that it would be desirable to determine the susceptibility of F. pedrosoi before initiating therapy, in order to choose the more effective antifungal and avoid clinical failure.

Antifungal Agents↗

PubMed2005

Posaconazole.

Posaconazole is a triazole antifungal agent, administered as an oral suspension, with an extended spectrum of in vitro activity. Posaconazole 800 mg/day demonstrated clinically relevant activity against a range of fungi in patients with invasive fungal infections who were refractory to, or intolerant of, other antifungal therapy in an open-label, multicentre, phase III study (330 patients received posaconazole and 279 patients served as external controls). In aspergillosis, the global response success rate at the end-of-therapy visit (primary endpoint) was significantly higher in posaconazole recipients than in external controls (42% vs 26%). Posaconazole was also associated with overall success rates of 54% in zygomycosis, 46% in fusariosis, 43% in Pseudallescheria infection, 80% in phaeohyphomycosis and 100% in histoplasmosis. Success rates were 48% in refractory candidiasis, 69% in refractory coccidioidomycosis, 48% in refractory cryptococcal infection and 82% in refractory chromoblastomycosis or mycetoma. Posaconazole also demonstrated potential in febrile neutropenia in an open-label phase II study (success rate of 81% 7 days after the end of treatment). In a noncomparative, multicentre, phase III study in patients with advanced HIV infection who had azole-refractory oropharyngeal and/or oesophageal candidiasis, posaconazole 400 or 800 mg/day resulted in a clinical response in 132 of 176 patients (75%). Oral posaconazole suspension was generally well tolerated in patients with invasive fungal infections, including patients who received treatment for >or=1 year.

Animals↗

PubMed2003

Therapeutic approaches to subcutaneous mycoses.

Subcutaneous mycoses, which are much less common than superficial fungal infections, are characterized by a heterogeneous group of infections that often result from direct penetration of the fungus into the dermis and subcutaneous tissue through traumatic injury. The fungus spreads by local deep tissue invasion from the inoculation site. The disease usually remains localized and then slowly spreads to adjacent tissue and eventually to the lymphatics. More rarely, hematogenous dissemination is observed. There are usually various clinical features and thus a broad range of differential diagnoses. The common subcutaneous mycoses are sporotrichosis, chromoblastomycosis, phaeohyphomycosis, eumycotic mycetoma, and hyalohyphomycosis. Many subcutaneous mycoses are confined to the tropical and subtropical regions, but some, such as sporotrichosis, are also prevalent in temperate regions. Subcutaneous mycoses can occur in healthy individuals. In immunocompromised individuals, these infections can disseminate widely. Treatment usually involves use of antifungal agents and/or surgical excision. Treatment of some serious subcutaneous mycoses remains unresolved, and there have been reports of relapses or progression during therapy and problems with lack of tolerability of antifungal drugs. Identification of the etiologic agent by culture is essential for prognostic and management considerations, since some fungi are more frequently associated with dissemination. Results of antifungal susceptibility tests may provide valuable information for deciding the appropriate method of treatment. Development of new antifungal agents and combination therapies may result in improvement in the management of subcutaneous mycoses in the future.

Antifungal Agents↗

PubMed1987

Black fungi: a survey of dematiaceous hyphomycetes from clinical specimens identified over a five year period in a reference laboratory.

Five hundred and fifty six dematiaceous hyphomycetes, the great majority referred from other laboratories, were identified by us over a five year period. Of these, thirty five were regarded as being of probable pathogenetic significance. These included seven isolates associated with chromoblastomycosis, and seven isolates thought to be causing phaeohyphomycosis. There were six strains of Phaeoannellomyces werneckii and five strains of Sporothrix schenckii. Seven isolates, all strains of Aureobasidium pullulans, were associated with fungal peritonitis in patients on chronic ambulatory peritoneal dialysis. Two Bipolaris isolates were associated with paranasal sinus fungus ball, a condition in which no evidence of tissue invasion by fungi could be found, even though pressure necrosis of bone could lead to very serious consequences. A further seven dematiaceous hyphomycetes, isolated from cases of paranasal fungus ball, keratitis and otitis externa, were thought to be of possible pathogenetic significance. Of the remaining 514 isolates thought to be of no pathogenetic significance, two thirds were made up of strains of Aureobasidium pullulans, Alternaria alternata, Cladosporium cladosporioides, Epicoccum purpurascens and Phoma species. In many cases it was thought that the referring laboratories had allowed insufficient time for development of conidiogenesis in these strains, before sending them to our laboratory for identification.

Humans↗

PubMed2002

[Human infections by black yeasts of genus Exophiala].

Clinical and laboratory aspects of the infections caused by Exophiala species are reviewed with regard to its epidemiology, diagnosis and treatment. Exophiala is a genus of dematiaceous hyphomycetes whose taxonomy and nomenclature undergo constant revision. Exophiala species are widely distributed in nature, and they are uncommon human pathogens. In recent years it appears to have increased its frequency as a cause of human infections, mainly in immunocompromised patients. They have been associated with phaeohyphomycosis, chromoblastomycosis, eumycotic mycetoma and disseminated infection. The procedures recommended for diagnosis consist of detection of fungal elements in tissue and growth of the organism in culture. Identification is mostly based upon microscopic observation of morphological characteristics and conidiogenesis, combined with the evaluation of physiological tests and nitrate and carbohydrate assimilations. Antifungal agents such as amphotericin B, itraconazole and voriconazole showed in vitro activity to most of the Exophiala species of clinical interest. The therapeutic recommendations are mainly deduced from the observation of single cases.

English Abstract↗

PubMedDate not supplied

A case report of phaeohyphomycosis caused by Cladophialophora bantiana treated in a burn unit.

Black molds are a heterogeneous group of fungi that are distributed widely in the environment and that occasionally cause human infection. The spectrum of disease includes mycetomas, chromoblastomycosis, sinusitis, and superficial, cutaneous, subcutaneous, and systemic phaeohyphomycosis. Cladophialophora bantiana, an agent of phaeohyphomycosis, causes rare infections mainly of the central nervous system. Extracerebral involvement is uncommon, and only a few cases have been reported. We present the case of a 32-year-old immunosuppressed female who developed a cutaneous phaeohyphomycosis from C. bantiana. The patient was treated in a burn unit with wound care, surgical excision, grafting, and itraconazole. Patients with complex fungal infections represent yet another population with specialized needs that are adequately met in a verified burn center.

Adult↗

PubMed1991

[The first isolation of Cladosporium cladosporioides (Fres.) de Vries from dental granulomas].

Thirteen Cladosporium have been isolated from 221 dental granulomas. Cases have been observed of cerebral lesions both in man and cats. Also various types of lesions, encapsulated abscesses, etc. to be classified under the group of pheoifomycoses. Cutaneous allergies and cases of keratitis and chromoblastomycosis have been observed, too Cladosporium cladosporioides is very resistant to mercuric and phenolic compounds and radiations. The systematic position and morphology of Cladosporium have been fully examined in accordance to the latest scientific views.

Adolescent↗

PubMed1986

The relationship of Phialophora verrucosa to Phialophora americana.

Phialophora verrucosa and P. americana, two dematiaceous hyphomycetes, are known to cause chromoblastomycosis. Even though most medical mycologists consider P. americana as synonymous with P. verrucosa, others maintain them as two distinct species on the basis that the phialides of P. americana have deeper collarettes than those of P. verrucosa. Thirty-two isolates, identified either as P. americana or P. verrucosa, were studied for their morphologic, physiologic, and antigenic characteristics to evaluate their taxonomic status. Collarette morphology was found to be a variable character in 12 of the 32 isolates. Those 12 produced phialides with both shallow and deep collarettes. All of the isolates hydrolysed urea within 7 days at 25 degrees C, and failed to liquefy gelatin after 3 weeks at 25 degrees C. None of the isolates decomposed casein, xanthine, or hypoxanthine at the end of 3 weeks at 25 degrees C. All decomposed tyrosine. They grew at 25 degrees C and 37 degrees C, but failed to grow at 40 degrees C. The antigenic relationship between the two species was studied by the exoantigen procedure. The 32 isolates showed close antigenic relatedness. Adsorptions of antisera with homologous and heterologous antigens rendered the antisera free of precipitin bands when studied by the microimmunodiffusion test. The depth of phialide collarettes produced by the two species, being found to be variable character, and the identical nature of the two species with respect to their physiologic and antigenic characteristics, led us to conclude that P. americana should be considered as a synonym of P. verrucosa.

Antigens, Fungal↗

PubMed1987

[Apropos of the origin of some diseases raging in Madagascar].

Madagascar had been separated from african continent since 5 millions years and, if flora and fauna are endemic (40 species of lemuriens) all of parasites and humans populations are imported, from africa with respect to P. falciparum, P. malariae, S. mansoni and S. haematobium (but snails are endemic ), Fasciola gigantica (imported with zebus) and perhaps P. vivax, and from Asia with respect to W. bancrofti, N. americanus, C. cellulosae (imported with pigs) and perhaps P. vivax, chromoblastomycosis is autochthonous and of high frequency. Malagasy were natives of Indonesia, Africa, Arabia and Europe.

Communicable Diseases↗

PubMed1980

Drugs for fungal infections.

The type of fungal infection and the immunologic status of the patient determine whether drug therapy should be used. Amphotericin B is the single most important antifungal agent for the treatment of systemic mycoses. Flucytosine is given adjunctively with amphotericin B. Miconazole, a new parenteral agent, may be useful in treating candidiasis, cryptococcosis, paracoccidioidomycosis and coccidioidomycosis. Potassium iodide is used to treat lymphocutaneous sporotrichosis, bronchopulmonary geotrichosis and chromoblastomycosis. Nystatin, tolnaftate, clotrimazole and haloprogin are used for mucocutaneous infections. Griseofulvin is limited to the treatment of skin and nail infections caused by dermatophytes.

Adult↗

PubMed1993

Itraconazole: pharmacokinetics and indications.

Itraconazole is a highly lipophilic triazolic compound, scarcely soluble in acidified polyethylene glycol, and soluble in hydroxypropyl-beta-cyclodextrin. It possesses an excellent digestive adsorption and its peak plasma level after oral administration of 100 mg is 0.16 microgram/ml at 3 or 4 h after drug intake. Half-life of itraconazole ranges between 17 to 21 h and 99.8% binds to plasmatic proteins, especially albumin. Metabolization is mainly done in the liver where inactive metabolites are formed with the exception of hydroxy-itraconazole, which exhibits a discrete antifungal activity. Stabilization of blood levels with repeated drug administration is reached at day 14, showing an increase both in plasma concentrations and in its half-life. Tissue levels of itraconazole are 3- to 20-fold higher than plasmatic concentrations, whereas only negligible concentrations are in CSF and urine. In the skin and particularly nails, itraconazole persists for a long time after discontinuation of therapy. Its mechanism of action is similar to other azolic compounds, inhibiting the alpha-14-demethylase of lanosterol which interferes with the synthesis of ergosterol. This drug behaves as a wide spectrum antifungal agent, acting against most pathogenic fungi with the exception of the Zygomycetes. Daily doses vary, according to indications, from 100 to 400 mg. The efficacy and results obtained in dermatomycosis, candidiasis, paracoccidioidomycosis, keratomycosis, sporotrichosis, chromoblastomycosis, coccidioidomycosis, blastomycosis, cryptococcosis, phaeohyphomycosis and maduromycotic mycetomas are detailed.

Humans↗

PubMedDate not supplied

Sex hormone effects on Phialophora verrucosa in vitro and characterization of progesterone receptors.

To determine the effects of sex steroid hormones on the growth of an aetiologic agent of chromoblastomycosis, we studied the dematiaceous fungus Phialophora verrucosa. The in vitro growth of this species on culture media containing either progesterone, testosterone or oestradiol at various concentrations was assessed. Both progesterone and testosterone inhibited the growth of P. verrucosa, whereas oestradiol did not. In other experiments, fungal cytosolic fractions were obtained and steroid binding assays were performed. These studies showed that the presence of progesterone receptors possessed two binding sites as determined by Scatchard analysis, one of which has a high affinity to progesterone (Kd = 6.02 x 10(-8) M) with total binding sites of 120 fmol micrograms-1 protein. These findings suggest that the growth of P. verrucosa is regulated by steroid hormones and that the effect of progesterone could be mediated through fungal intracellular progesterone receptors.

Antifungal Agents↗

PubMed1962