Ketoconazole was administered orally in daily doses of 200 mg to 70 patients with onychomycosis. Complete recovery was attained by 48 patients, improvement of > 50% by 10 patients, and for three patients therapy failed. For the remaining nine patients the results could not be evaluated. The average duration of treatment was 7.5 months for disease due to Trichophyton species and 6.5 months for disease due to Candida species. There were no adverse effects or signs of toxicity attributable to the administration of ketoconazole. It is concluded that ketoconazole is a positive development in the effort to control the difficult problems presented by onychomycosis.

Adolescent↗

PubMedDate not supplied

Ketoconazole in the treatment of paracoccidioidomycosis and histoplasmosis.

Ketoconazole was given orally to 33 patients with paracoccidioidomycosis and 23 with histoplasmosis. There were 55 men and one woman, and ages ranged from 28 to 67 years. Each patient had either the chronic disseminated or the chronic pulmonary form of disease. The diagnosis was established in 54 patients by culture of Paracoccidioides brasiliensis or Histoplasma capsulatum from lesions and in two patients by the clinical picture and results of serologic tests for histoplasmosis. The initial dosage was 400 mg per day. The dosage was reduced to 200 mg when a cure was achieved. The duration of treatment ranged from two to 18 months. Results of treatment were classified as very good (clinical and serologic cure) in 23 (41%) of the patients; good (clinical cure only) in 28 (50%); fair (partial improvement) in one (2%); and poor (no improvement) in three (5%). The results were not assessable in one patient who did not complete therapy. The three patients who did not respond to treatment had less than or equal to 0.19 microgram of ketoconazole/ml in their blood. The drug was well tolerated, and no side effects were reported.

Administration, Oral↗

PubMedDate not supplied

Oral treatment of paracoccidioidomycosis and histoplasmosis with itraconazole in humans.

Twenty-five patients with paracoccidioidomycosis and 17 patients with histoplasmosis were treated with itraconazole. All patients were adults. Those with paracoccidioidomycosis exhibited the chronic disseminated form of the disease; 21 of these patients had lesions in two or more locations, and four had lesions only on the larynx or mouth. Itraconazole was administered at a daily dosage of 50 mg for six months in the majority of these cases. All infections were clinically cured or showed striking improvement. Patients with histoplasmosis had the chronic pulmonary or chronic disseminated form of the disease. A daily dose of 100 mg was administered until clinical cure was established; the dose was then changed to 50 mg until the completion of six months of treatment. Twelve infections were clinically cured; four were strikingly alleviated. The remaining patient, who discontinued treatment with itraconazole after two months, had a severe relapse and died of respiratory failure.

Administration, Oral↗

PubMedDate not supplied

[Cutaneous phycomycosis of pseudo-mycetoma type with pronounced hepato-splenomegaly].

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Adolescent↗

PubMedDate not supplied

Itraconazole in the treatment of histoplasmosis associated with AIDS.

Twenty-seven patients suffering AIDS and disseminated histoplasmosis were included in this study, comprising twenty-three males and four females, from 18 to 46 years of age (mean = 32.9). The most frequent clinical manifestations were fever, weight loss, anaemia, skin lesions, pulmonary micronodules, hepatosplenomegaly and adenomegalies. All of them presented other infectious diseases or neoplasias frequently found in AIDS patients. The diagnosis of histoplasmosis was based upon the finding of Histoplasma capsulatum in microscopic examination or in cultures from the following specimens: skin scrapings, bone marrow aspiration, bronchoalveolar lavage, blood cultures, buccal biopsies and lymph node biopsy. Serologic reactions, searching for antibodies, were positive in 11 cases. Itraconazole by oral route, at a daily dose of 200 mg (24 cases) or 400 mg (3 cases), was administered for 6 months. Those patients who were clinically cured after receiving this scheme of treatment were treated with itraconazole 100 mg day-1 as a suppressive therapy. Twenty-three patients were considered responders, 1 as a non-responder and 3 non-assessable. The average survival time was 7.8 months and eleven cases are still alive. Itraconazole proved to be a useful medication in disseminated histoplasmosis associated with AIDS and it was very well tolerated.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Itraconazole and flucytosine+itraconazole combination in the treatment of experimental cryptococcosis in hamsters.

The efficacy of two different daily doses of itraconazole (ITRA) and the combination of flucytosine (5-FC) with ITRA in the treatment of an experimental model of cryptococcosis in hamsters was studied. Five groups of 20 animals each were inoculated by the intracardiac route with 10(5) cells of Cryptococcus neoformans. Treatment started 3 days after the infection, and was administered by gavage for 30 days. ITRA was applied at a daily dose of 25 mg kg-1 or 50 mg kg-1 and the combination of 5-FC and ITRA was given at 75 mg kg-1 day-1 or 50 mg kg-1 day-1 respectively. One group of 20 hamsters received the vehicle and was used as a control group. Treatment evaluation was based on the following parameters: number of surviving animals 60 days after the infection; presence of encapsulated yeasts on microscopic examination of wet preparations of brain, lungs, liver, spleen and kidneys at necropsy; and brain qualitative (massive seeding) and quantitative cultures (determination of colony forming units, CFU). ITRA 50 (50 mg kg day-1) was the most effective treatment according to the studied parameters; 70% of brain cultures became negative and 95% of the treated hamsters survived to the end of the study period. ITRA efficacy was dose dependent. The combination of ITRA with 5-FC was less effective than administering the drugs separately; the reason for this finding is not known. The results obtained in this study should encourage the use of high doses of ITRA in cases of disseminated cryptococcosis in humans.

Animals↗

PubMedDate not supplied

Safety evaluation of chronic fluconazole therapy. Fluconazole Pan-American Study Group.

The possible adverse effects of chronic, high-dose fluconazole therapy are detailed from analysis of a multicenter, dose-escalating study of the therapy of invasive mycoses. Ninety-three adult patients were studied, 48 of these received > or = 6 months therapy and 20 received > or = 1 year. Fifty-eight patients received > or = 300 mg/day, and 7 received > or = 600 mg/day. One patient received 1,997 g over 86 months. Twenty-seven percent experienced possible symptomatic side effects, which resulted in 2 patients discontinuing therapy, and 42% had asymptomatic laboratory abnormalities, none of which were progressive. Headache, hair loss and anorexia were the most common symptoms experienced (each by 3% of patients), and eosinophilia and aspartate aminotransferase increases were the most common laboratory findings (12 and 10%, respectively). Fluconazole appears well tolerated and safe in these doses and durations.

Adult↗

PubMedDate not supplied

Epidemiologic study of bronchopulmonary mycosis in the province of Cordoba, Argentina.

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Adolescent↗

PubMedDate not supplied

Isolation of human fungi from soil and identification of two endemic areas of Cryptococcus neoformans and Coccidioides immitis.

The present study was carried out in two different areas of Province of Cordoba, Argentina, where there was a suspicious of endemic mycosis. The previous data were the presence of a clinical case of pulmonary cryptococcosis in one area (Alta Gracia) and the previous findings of a high incidence of coccidioidin and cryptococcin reactors in the population of the second one (Villa Dolores). In both areas soil samples for fungi were studied and Cryptococcus neoformans was found in 2/25 samples from Alta Gracia. In Villa Dolores Coccidioides immitis was isolated in 2/40 samples, and C. neoformans in 1/40 samples. Delayed hypersensitivity test with cryptococcin was determined in the population from Alta Gracia and it was found to be 5.3%. Positive cutaneous tests with coccidioidin (33.8%) and cryptococcin (31.9%) in Villa Dolores were obtained. With these findings two endemic areas of systemic mycoses in Cordoba, Argentina were delimited.

Adolescent↗

PubMedDate not supplied

[In vitro susceptibility of Cryptococcus strains to 5 antifungal drugs].

A comparative study of the "in vitro" susceptibility of 24 Cryptococcus strains to 5 antifungal drugs (amphotericin B, 5 fluorocytosine, miconazole, itraconazole and ketoconazole), was carried out. These strains were grouped according to species, varieties and isolation's origins. The minimum inhibitory concentration (M.I.C.) was determined by the agar dilution technique in yeast nitrogen base agar with dextrose. The mean geometrical of the M.I.C. values of each group was compared with the others. The results obtained were homogeneous with the only exception of the "non neoformans" strains, in which, higher M.I.C. to 5 fluorocytosine values were detected.

Amphotericin B↗

PubMedDate not supplied

Cyclophosphamide effect on coccidioidomycosis in the rat.

Cocidioidomycosis is a systemic mycosis, endemic in arid areas of the American continent. The rat was employed as an experimental host, since it had been shown to reproduce human lesions and present a chronic course of disease with granulomas mainly restricted to lungs. Given the influence of immunosuppressive therapy on the clinical course of human coccidioidomycosis, we studied the effect of cyclophosphamide (CY) in the experimental rat model. Accordingly, animals were inoculated with 400 Coccidioides immitis arthroconidia of the Acosta strain, by intracardiacal route. As single CY doses failed to alter the course of disease, three schedules were used: A) 4 daily doses of 20 mg/kg each, prior to C. immitis inoculation; B) 4 similar daily doses after infection; and C); 6 doses of 20 mg/kg each, given from day +1 to +4 then on days +8 and +9, post infection (pi), taking day 0 as the time of fungal inoculation. The first two schedules inhibited antibody formation up to day 28 pi, without modifying cellular response to coccidioidin as measured by foodpad swelling. Initially, there was greater fungal spread than in controls receiving C. immitis alone, which proved self-limiting in the latter. In contrast, schedule C led to 55% mortality with both humoral and cellular response abrogation, accompanied by extensive C. immitis dissemination. Histology disclosed significant alterations, such as the persistence of primary infection sporangia, corresponding to the acute stage of coccidioidomycosis in the absence of granuloma development. Therefore, the observed depression in cellular immunity seems responsible for the lack of inflammatory reaction capable of restricting sporangia proliferation in tissues which, in turn, enhances pathogen spread and mortality rate.

Animals↗

PubMedDate not supplied

[E.L.I.S.A. in human coccidioidomycosis].

An E.L.I.S.A. test for antibody detection, with an exo-antigen of Coccidioides immitis was standardized in 67 humans sera diluted in 1/1000, 1/2000, 1/4000 and 1/8000. Eighteen sera from mycologically proved cases of coccidioidomycosis were studied: 5 were negative and 13 were positive in some dilutions. 3/26 sera of healthy persons who presented positive skin tests with coccidioidin were positive and the other 23 sera did not have positive reactions. None of the 15 sera of healthy human exhibited positive E.L.I.S.A. Serum samples of 8 patients suffering other deep mycosis were studied, 4 of them presented cross-reactions in E.L.I.S.A. tests. E.L.I.S.A. test seems to be a useful serologic technique for antibody detection in anticomplementary serum samples or when a low concentration of antibodies should be detected. As it is very sensitive, cross-reactions with other mycoses are frequent, thus the use other more specific serologic technique together E.L.I.S.A. is recommended.

Adult↗