Chemotherapeutic agents for the pulmonary mycoses. Report of the Committee on Fungus Diseases and Subcommittee on Therapy, American College of Chest Physicians.
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The pathological findings of the cerebral involvement in deep-seated fungal infections in routine autopsy is reported. In 42 cases of mycotic infections studied among 3.966 autopsies, there were 8 cases of cryptococcosis and 2 of aspergillosis of the brain, showing a very low frequency of central nervous system involvement, occurring in a proportion of 1:400 autopsies. The histopathological findings of the brain in cases of cryptococcosis showed the spectrum of inflammatory reactions already described, although most of the cases presented with mild to severe meningitis with large number of giant cells, and slight degree of involvement of the nervous tissue. The cases of aspergillosis showed a pattern of severe necrotizing meningo-encephalitis with large number of fungi. The paper points out the role of the histological examination in the identification of the fungi in tissues and their morphologic reactions.
Xacriabá Indian Reserve is situated in the north of Minas Gerais State, Brazil, near the municipality of Manga and São Francisco River. The Indian population is miscegenated with caucasian and negroid people and have farming activities. Blood samples were collected from 180 inhabitants of the reserve (85 men and 95 women), 15 to 84 years old. Serum antibodies against antigens of Paracoccidioides brasiliensis, Histoplasma capsulatum, Cryptococcus neoformans, and Candida albicans were tested for by counterimmunoelectrophoresis method. Seropositivity was verified in 5%, 3.9%, 4.2%, and 6.7%, respectively of the 180 samples. Those seropositive for antigens of P. brasiliensis and H. capsulatum were predominantly women and had lower age and more elevated mean titers of antibodies than individuals whose sera reacted with antigens of C. neoformans and C. albicans. The results suggest the occurrence of paracoccidioidomycosis-infection and histoplasmosis-infection in the Xacriabá Indian Reserve, particularly in the first decades of life of the inhabitants.
Terbinafine is an orally and topically active allylamine antifungal agent with a primarily fungicidal action in vitro. Its spectrum of in vitro activity includes a broad range of dermatophyte, filamentous, dimorphic and dematiaceous fungi, and some yeast species. In clinical trials, mycological and overall efficacy rates of around 90 and 80%, respectively, have been achieved in cutaneous dermatophyte infections (tinea corporis/cruris and tinea pedis) with terbinafine, administered either orally (250 or 500 mg/day) or topically (a 1% cream applied twice daily). Similar rates of cure have been obtained with oral terbinafine in dermatophyte nail infections after relatively short treatment periods ranging from 3 to 12 months. Topical terbinafine has been effective in approximately 80% of patients with cutaneous candidiasis or pityriasis versicolor. Few comparative data have been published, but generally oral terbinafine appeared to be at least as effective as oral griseofulvin or ketoconazole in tinea corporis/cruris and more effective than griseofulvin in tinea pedis. Both oral and topical terbinafine have been very well tolerated in clinical trials to date, with only minor adverse effects reported. Although further research is required to establish the efficacy of terbinafine in comparison with other available therapies, as well as to fully clarify its tolerability profile, the early results obtained with terbinafine in superficial fungal infections are very encouraging. Terbinafine appears likely to become a first-line therapy for dermatophyte infections, particularly those affecting the nails.
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Clinical evaluation was retrospectively made of the results of serological diagnostic methods using plasma and/or sera of patients for the diagnosis of aspergillosis, candidosis, and pneumocystosis. Specimens were drawn from 8 patients with invasive aspergillosis, 3 with aspergilloma, 9 with candidosis, 4 with pneumocystosis, and 15 with no fungal infections. In invasive aspergillosis, the sensitivities of the (1-3)-beta-D-glucan measurement test using chromogenic and turbidimetric methods were 78.6% and 82.1%, with specificities of 75% and 87.5%, respectively. The sensitivity of the Pastorex Aspergillus test for invasive aspergillosis was 16.7%, with a specificity of 92.3%. In candidosis, the sensitivities of the (1-3)-bata-D-glucan test using the above two methods were 84.2% and 100%, with specificities of 75% and 87.5%, respectively. The sensitivity of the CAND-TEC test and the Pastorex Candida test for candidosis were 68.8% and 16.7%, with specificities of 57.1% and 100%, respectively. These results indicate that the (1-3)-bata-D-glucan measurement methods are more reliable in clinical application than the other antigen detection methods, but they still lack efficiency in differentiating fungal infections such as aspergillosis, candidosis and pneumocystosis. For a more exact diagnosis of systemic fungal infections, detailed studies on the clinical symptoms are considered essential.
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OBJECTIVE: To determine the efficacy and safety of fluconazole treatment of coccidioidal meningitis. DESIGN: Uncontrolled clinical trial. SETTING: Four university-based treatment centers in California, Arizona, and Texas. Most therapy was conducted without hospitalization. PATIENTS: Fifty consecutive patients with active coccidioidal meningitis, of which 47 (94%) were evaluable. Twenty-five patients had received no previous treatment for their meningitis, and nine had coinfection with human immunodeficiency virus (HIV). INTERVENTION: Fluconazole was administered in an oral dose of 400 mg once per day for up to 4 years (median, 37 months) in responding patients. Concurrent therapy with another antifungal agent was prohibited. MEASUREMENTS: Predefined assessment of infection-related abnormalities was done at the time of enrollment and was repeated at least every 4 months during treatment. Elimination of 40% or more of baseline abnormalities was considered a response. RESULTS: Thirty-seven of 47 (79%; 95% CI, 61% to 90%) evaluable patients responded to treatment. Response rates were similar for patients with and without previous therapy, for patients with and without concomitant HIV infection, and for patients with and without pre-existing hydrocephalus. Most improvement occurred within 4 to 8 months after starting treatment. Patient symptoms resolved more quickly than did cerebrospinal fluid abnormalities. In 15 of 20 responding patients followed for 20 months or more, residual low-level cerebrospinal fluid abnormalities remained throughout therapy. No patient discontinued therapy because of drug-related side effects, although confusion developed in two patients that resolved when the dose of fluconazole was reduced. CONCLUSION: Fluconazole therapy is often effective in suppressing coccidioidal meningitis.
BACKGROUND: In previous open-label noncomparative clinical trials, both fluconazole and itraconazole were effective therapy for progressive forms of coccidioidomycosis. OBJECTIVE: To determine whether fluconazole or itraconazole is superior for treatment of nonmeningeal progressive coccidioidal infections. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: 7 treatment centers in California, Arizona, and Texas. PATIENTS: 198 patients with chronic pulmonary, soft tissue, or skeletal coccidioidal infections. INTERVENTION: Oral fluconazole, 400 mg/d, or itraconazole, 200 mg twice daily. MEASUREMENTS: After 4, 8, and 12 months, a predefined scoring system was used to assess severity of infection. Findings were compared with those at baseline. RESULTS: Overall, 50% of patients (47 of 94) and 63% of patients (61 of 97) responded to 8 months of treatment with fluconazole and itraconazole, respectively (difference, 13 percentage points [95% CI, -2 to 28 percentage points]; P = 0.08). Patients with skeletal infections responded twice as frequently to itraconazole as to fluconazole. By 12 months, 57% of patients had responded to fluconazole and 72% had responded to itraconazole (difference, 15 percentage points [CI, 0.003 to 30 percentage points]; P = 0.05). Soft tissue disease was associated with increased likelihood of response, as in previous studies. Azole drug was detected in serum specimens from all but 3 patients; however, drug concentrations were not helpful in predicting outcome. Relapse rates after discontinuation of therapy did not differ significantly between groups (28% after fluconazole treatment and 18% after itraconazole treatment). Both drugs were well tolerated. CONCLUSIONS: Neither fluconazole nor itraconazole showed statistically superior efficacy in nonmeningeal coccidioidomycosis, although there is a trend toward slightly greater efficacy with itraconazole at the doses studied.
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