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.

Fluconazole: pharmacokinetics and indications.

Fluconazole is a new systemic azole antifungal agent, with the imidazole group substituted by a triazole, presenting a decrease in lipophilicity, soluble in water, weakly bound to plasma proteins, and a wide range of formulations. The time to reach steady-state with a once daily dosage is approximately 7 days. Distribution of fluconazole is extensive and even throughout the tissues, and the drug circulates as a free drug. Half-life elimination is approximately 30 h. Indications are given for fungal infections in AIDS patients and mycoses.

A Pan-American 5-year study of fluconazole therapy for deep mycoses in the immunocompetent host. Pan-American Study Group.

Eighty-eight immunocompetent patients with deep mycoses from eight countries were evaluated with the same protocol for efficacy of fluconazole monotherapy. Entry doses were raised from 100 to 400 mg as safety was shown in initial cohorts, and dosages up to 2,400 mg daily and durations up to 44 months were studied. Results were very similar in different countries. Twenty-seven of 28 evaluable patients with paracoccidioidomycosis, 13 of 19 with sporotrichosis, 14 of 16 with coccidioidomycosis, and eight of eight with histoplasmosis demonstrated objective responses to therapy, as did one patient each with zygomycosis and alternariosis. For these patients, relapses have been unusual thus far. In contrast, one patient with chromoblastomycosis responded but relapsed, and six did not respond; one patient with mycetoma responded but relapsed, and two did not respond. The drug was well tolerated by patients, including six who received intravenous therapy. In vitro susceptibility tests suggested that clinical response was correlated with susceptibility but that resistance did not preclude clinical response. Fluconazole therapy appears efficacious for several deep mycoses; dosages of greater than 200 mg daily may be needed for some diseases. The further evaluation of fluconazole for these entities is warranted.

Therapy with fluconazole for tinea corporis, tinea cruris, and tinea pedis.

We treated 20 patients who had tinea corporis and/or tinea cruris and 20 patients who had tinea pedis with oral fluconazole. All patients were given a single 150-mg dose of fluconazole upon entry into the study; at that time, and at each follow-up visit, clinical signs and symptoms were evaluated and mycological and laboratory examinations were performed. If clinical and/or mycological cure or significant improvement in a patient's condition was not evident at the 7-day follow-up visit, a second dose of fluconazole (150 mg) was given. A maximum of four doses, one week apart, were given. A long-term evaluation of the efficacy of fluconazole in the treatment of these infections was performed 28-30 days after the last dose was administered to each patient. For the treatment of tinea corporis and/or tinea cruris, 70% of patients required two doses, 20% required three doses, and 10% required four doses. At the long-term follow-up visit the clinical and mycological response rates were determined to be 95% cure and 5% relapse. For the treatment of tinea pedis, 20% of the patients required two doses, 20% required three doses, and 60% required four doses. For these patients, the long-term clinical response rates were 70% cure and 30% improvement; mycological response rates were 75% eradication, 10% persistence of infection, and 15% relapse. This treatment was well tolerated; no adverse effects or clinically significant laboratory abnormalities were reported.

Doses unicas semanais orais de fluconazol 150 mg no tratamento de tinea corporis/cruris e candidiase cutanea / Doses weekly only you pray of fluconazol 150 mg in the treatment of cutaneous tinea corporis/cruris and candidiasis

Noventa e cinco pacientes ambulatoriais com tinea corporis e/ou tinea cruris participaram de um estudo multicentrico nao comparativo aberto para investigar a seguranca e eficacia de 1-4 doses unicas semanais de fluconazol oral na dose de 150 mg. O trichophyton rabrum foi o organismo mais frequentemente isolado (67 de 86 pacientes avaliados micologicamente). Uma media de 2,6 doses de fluconazol foi administrada; pacientes infectados com Candida albicans ou Epidermophyton floccosum necessitaram, em media, de 2 doses enquanto foram necessarias 3-4 doses em pacientes infectados com outros organismos. A cura clinica foi obtida em 85 de 92 (92%) dos pacientes na ultima avaliacao depois do tratamento, tendo os sete pacientes restantes melhorado substancialmente. No seguimento a longo prazo, 28-30 dias apos a ultima dose, 80 de 91 (88%) pacientes foram considerados clinicamente curados, tres (3%) apresentaram melhora e oito (9%) tiveram insucesso terapeutico. Dentre os fracassos clinicos a longo prazo, houve um diagnostico de tinea corporis (3%) de taxa de insucesso) e sete diagnosticos de tinea cruris (12% de taxa de insucesso). Evidencias micologicas de infeccao ocorreram em apenas 1 de 86 pacientes seguidos ate o final do seguimento a longo prazo. Recidiva micologica ocorreu em nove (11%) dos pacientes do seguimeto a longo prazo; um paciente estava infectado pelo Trichophyton mentagrphytes e oito pacientes, pelo T. rubrum. Houve recidiva em 2 de 29 (7%) pacientes com tinea corporis e oito de 57 (14%) com tines cruris (um paciente que recidivou tinha tinea corporis e cruris). Nao se verificou correlacao entre o numero de doses recebidas e a resposta micologica ou as taxas de recidiva a longo prazo. O fluconazol foi bem tolerado; somente 5 de 95 pacientes tratados com fluconazol referiram efeitos adversos, um dos quais resultou em descontinuacao da terapia (urticaria moderada). A boa tolerancia comparada a dos outros antifugicos orais e a conveniencia de um esquema de dose unica semanal oral em comparacao aos tratamentos topicos e orais existentes tornam a dose unica oral semanal de fluconazol uma elternativa valiosa no tratamento da tinea corporis/cruris

[Chromomycosis. Treatment with a combination of thiabendazole and 5-fluorocytosine, 6-year follow-up]. / Cromomicosis. Tratamiento con la asociación thiabendazole y 5-fluorocitosina, seis años de seguimiento.

The results of the treatment of 30 cases of chromomycosis (fonsecal pedrosoi) with Thiabendazole (1 g.) and 5. Fluorocytosine (4 g.) are reported. The medium rate of healing was 7,63 months. This treatment was effective in 25 of 30 cases (83 por 100) and ono-effective in 3 (10 por 100). In 2 cases recurrences occurred (6,66 por 100).

Chromoblastomycosis: Host-parasite interactions

FROM THE CASES STUDIED BY OUR WORK GROUP IN THE DERMATOLOGY SERVICE OF THE HOSPITAL SAN JUAN DE DIOS UNDER THE DIRECTION OF PROFESSOR ELFREN SOLANO, WE CHOSE FIVE FOR DISCUSSION OF THE HOST-PARASITE RELATIONSHIP