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We present the case of a twenty six year-old woman with rheumatoid arthritis, treated with certolizumab. She sought medical attention due to cough, fever and night sweats. X-ray exam showed a miliary pneumonia. She was treated for tuberculosis and 50days later she presented with aphasia. Magnetic nuclear resonance revealed brain lesions. Histoplasma capsulatum PCR test and urinary antigen were positive, so an antifungal treatment with voriconazole was started. Visual adverse effects forced to change the antifungal schedule in both the length of treatment and the antifungal drug. With this measure the patient progressed favorably. The test of urinary Histoplasma capsulatum antigen and PCR amplification were key to make a diagnosis and also for a follow-up., (Copyright © 2023 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Classic histoplasmosis is a systemic endemic mycosis due to Histoplasma capsulatum var. capsulatum. A significant reduction in the morbidity and mortality of AIDS-related histoplasmosis has been observed since the introduction of highly active antiretroviral therapy (HAART) and secondary antifungal prophylaxis., Aims: The aim of this study was to determine the current state of prognosis and treatment response of HIV-positive patients with histoplasmosis in the Francisco J. Muñiz Infectious Diseases Hospital in Buenos Aires City., Methods: A retrospective study was conducted using the demographic, clinical, immunological and treatment data of 80 patients suffering from AIDS-related histoplasmosis., Results: Of the 80 cases studied 65 were male, the median age was 36 years, with 73.7% of the patients being drug addicts, 82.5% of the patients was not receiving HAART at diagnosis, and 58.7% of the cases had less than 50 CD4+ cells/μl at the beginning of the treatment. The initial phase of treatment consisted of intravenous amphotericin B and/or oral itraconazole for 3 months, with 78.7% of the cases showing a good clinical response. Only 26/63 patients who were discharged from hospital continued with the follow-up of the HAART, secondary prophylaxis with itraconazole or amphotericin B. Secondary prophylaxis was stopped after more than one year of HAART if the patients were asymptomatic, had two CD 4 + cell counts greater than 150cells/μl, and undetectable viral loads. No relapses were observed during a two-year follow up after prophylaxis was stopped., Conclusions: The treatment of histoplasmosis in HIV-positive patients was effective in 78.8% of the cases. The combination of HAART and secondary antifungal prophylaxis is safe, well tolerated, and effective. The low adherence of patients to HAART and the lack of laboratory kits for rapid histoplasmosis diagnosis should be addressed in the future. The usefulness of primary antifungal prophylaxis for cryptococcosis and histoplasmosis HIV-positive patients should be studied., (Copyright © 2016 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Current therapy for mycoses is limited to the use of a relative reduced number of antifungal drugs. Although amphotericin B still remains considered as the "gold standard" for treatment, acute and chronic toxicity, such as impairment of renal function, limits its use and enhances the investigation and clinical use other chemical families of antifungal drugs. One of these chemical class of active drugs are azole derivatives, discovered in 70s and introduced in clinical practice in 80s. Being the most prolific antifungal class, investigation about more molecules, with a safer and better pharmacological profile, active against a wide spectrum of fungi, with a wide range of administration routes gives us some azole representatives.

Background: Intracranial fungal masses are uncommon diseases, but their incidence is increasing, most often due to the prolonged survival of patients with different immunodeficiencies. The management of patients with intracranial fungal masses included stereotactic biopsy for diagnosis, partial or radical surgery excision and prolonged antifungal therapy., Aims: We report the case of a 51-year-old diabetic man with a history of psoas abscess due to Candida albicans 1 year before the onset of neurological symptoms, including headache and generalized tonoclonic seizures., Methods: Magnetic resonance imaging showed a single lesion located in the right parietal lobe with mass effect, surrounding edema and enhancement after injection of gadolinium. The material was purulent., Results: Direct microscopic examination showed hyaline, branched and septate hyphae compatible with fungal elements., Conclusions: Fungal infections, especially due to Candida species, should be considered in diabetic patients with parenchymal brain abscesses. Radical excision followed by prolonged antifungal therapy based on fluconazole or amphotericin B is necessary to improve the prognosis of this type of patients., (2009 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.)

Physicians have been aware of superficial fungal infections for centuries, but the causal agents and treatments of fungal infections remained unknown until the mid-1800s, when numerous important findings were reported. Among the relevant researchers in the field of superficial mycoses were Remak, who found the fungal nature of favus in 1837; Berg, who reported oral candidosis in 1841; and Wilkinson, who described vaginal candidosis in 1849. Tinea versicolor was described clinically in 1846 by Eichstedt, and its etiologic agent was identified in 1853. Beigel reported white piedra in 1856, and Cerqueira, tinea nigra in 1891. The book Les Tiegnes was published by Sabouraud in 1910, and black piedra infection was described by Horta in 1911. In 1927, Nannizzi reported the description of the sexual state of Microsporum gypseum. The current classification of dermatophytes was published by Emmons in 1934, and the taxonomy of yeast fungi was described by Lodder and Kreger-van Rij in 1952. Finally, the successful treatment of tinea capitis with griseofulvin by Gentles in 1958 saved many patients with tinea capitis from permanent hair loss, a common side effect after treatment with thallium. (c) 2010 Elsevier Inc. All rights reserved., (Copyright 2010 Elsevier Inc. All rights reserved.)

Vulvovaginal candidiasis is a condition that affects a great number of fertile women. It is considered the second cause of genital infection after vaginosis due to GAM complex. Candida albicans is the most frequent isolated species from vaginal discharge. However, sometimes more than one yeast species could be found in the same clinical sample that are more resistant to antifungal drugs. Nowadays, it is necessary to identify properly up to species level the isolated microorganism and to determine the antifungal susceptibility profile. One hundred strains obtained from vaginal discharge of 94 patients suffering acute vulvovaginal candidiasis were studied. The identification of the isolates showed: C. albicans 86%, Candida glabrata 6%, Candida inconspicua 3%, Candida krusei 2% and Candida intermedia, Candida holmii and Trichosporon asahii one case each. Minimal inhibitory concentrations (MIC) of all the yeasts against fluconazole and albaconazole were performed. C. glabrata, C. krusei and C. inconspicua were the most resistant against fluconazole, on the other hand albicans was susceptible to this drug. All the isolates presented MIC against albaconazole much lower than fluconazole.

Six patients received salvage treatment with posaconazole oral suspension (800 mg/day in divided doses) for severe forms of histoplasmosis. One patient had pulmonary disease and 5 had disseminated disease. Previous antifungal therapy consisted of amphotericin B, itraconazole, fluconazole, or voriconazole. Posaconazole treatment duration for individual patients ranged from 6 weeks to 34 weeks. All patients had successful clinical outcomes with significant clinical improvements noted during the first month of therapy. Although the number of patients evaluated in this case series is small, the findings are encouraging and provide preliminary evidence that posaconazole may be a useful salvage treatment option for histoplasmosis involving a variety of infected tissues and organs.

Background: Invasive fungal infections are found most frequently in immunosuppressed and critically ill hospitalized patients. Antifungal therapy is often required for long periods. Safety data from the clinical development program of the triazole antifungal agent, posaconazole, were analyzed., Methods: A total of 428 patients with refractory invasive fungal infections (n = 362) or febrile neutropenia (n = 66) received posaconazole in 2 phase II/III open-label clinical trials. Also, 109 of these patients received posaconazole therapy for > or = 6 months. Incidences of treatment-emergent, treatment-related, and serious adverse events and abnormal laboratory parameters were recorded during these studies., Results: Treatment-emergent, treatment-related adverse events were reported in 38% of the overall patient population. The most common treatment-related adverse events were nausea (8%) and vomiting (6%). Treatment-related serious adverse events occurred in 8% of patients. Low rates of treatment-related corrected QT interval and/or QT interval prolongation (1%) and elevation of hepatic enzymes (2%) were reported as adverse events. Treatment-emergent, treatment-related adverse events occurred at similar rates in patients who received posaconazole therapy for < 6 months and > or = 6 months., Conclusions: Prolonged posaconazole treatment was associated with a generally favorable safety profile in seriously ill patients with refractory invasive fungal infections. Long-term therapy did not increase the risk of any individual adverse event, and no unique adverse event was observed with longer exposure to posaconazole.

Eumycetoma and chromoblastomycosis are chronic, disfiguring fungal infections of the subcutaneous tissue that rarely resolve spontaneously. Most patients do not achieve sustained long-term benefits from available treatments; therefore, new therapeutic options are needed. We evaluated the efficacy of posaconazole, a new extended-spectrum triazole antifungal agent, in 12 patients with eumycetoma or chromoblastomycosis refractory to existing antifungal therapies. Posaconazole 800 mg/d was given in divided doses for a maximum of 34 months. Complete or partial clinical response was considered a success; stable disease or failure was considered a nonsuccess. All 12 patients had proven infections refractory to standard therapy. Clinical success was reported for five of six patients with eumycetoma and five of six patients with chromoblastomycosis. Two patients were reported to have stable disease. As part of a treatment-use extension protocol, two patients with eumycetoma who initially had successful outcome were successfully retreated with posaconazole after a treatment hiatus of > 10 months. Posaconazole was well tolerated during long-term administration (up to 1015 d). Posaconazole therapy resulted in successful outcome in most patients with eumycetoma or chromoblastomycosis refractory to standard therapies, suggesting that posaconazole may be an important treatment option for these diseases.

Objectives: A multinational, multicentre, open-label clinical trial was conducted to evaluate the safety and efficacy of posaconazole, an extended-spectrum triazole antifungal agent, in subjects with invasive fungal infections who had refractory disease or who were intolerant of standard antifungal therapy. In this subanalysis, we report on those subjects in this trial who had a fungal infection that involved the CNS., Methods: Subjects received posaconazole oral suspension 800 mg/day in divided doses for up to 1 year; however, subjects could receive additional therapy as part of a treatment-use extension protocol. A blinded, third-party data review committee determined subject eligibility and outcome., Results: Of the 330 subjects who enrolled in the study, 53 had infections of the CNS, of which 39 were considered evaluable for efficacy. Most had refractory disease (37 of 39) and underlying HIV infection (29 of 39). Twenty-nine subjects had cryptococcal infections, and 10 had infections caused by other fungal pathogens [Aspergillus spp. (four), Pseudallescheria boydii (two), Coccidioides immitis (one), Histoplasma capsulatum (one), Ramichloridium mackenziei (one), and Apophysomyces elegans plus a Basidiomycetes sp. (one)]. Successful outcomes were observed in 14 of 29 (48%) subjects with cryptococcal meningitis and five of 10 (50%) subjects with CNS infections due to other fungal pathogens. Posaconazole was well tolerated., Conclusions: These data suggest that posaconazole, as an oral medication, has clinical activity against fungal infections of the CNS and may provide a valuable alternative to parenteral therapy in patients failing existing antifungal agents.

The clinical and laboratory data of 22 patients with AIDS related cryptococcosis who were able to interrupt antifungal secondary prophylaxis after HAART administration, are presented. They were 14 males and 8 females, between 15 and 50 years old (X: 34 years old). All patients presented fever and severe deterioration of their general health status, and 19 exhibited a meningeal syndrome. At the start of antifungal treatment, 59% of the cases presented < 50 CD4+ cells/microl, the median viral burden was 134,804 RNA copies/ml and the median titer of serum cryptococcal antigen was 1/3,000. Amphotericin B by intravenous route, (0.7 mg/kg/day) or fluconazole (600 to 800 mg/day) were given as a treatment of the initial episode, up to CSF cultures negativization. Oral fluconazole (200 mg/day) or intravenous amphotericin B, 50 mg twice a week, were given as a secondary prophylaxis. The secondary prophylaxis was interrupted when the patients had received HAART for an average lapse of 19 months (6 to 36 months) and the median CD4+ cell count was 249/microl. The follow up after secondary prophylaxis discontinuation lasted for a median lapse of 22 months. These data seem to show that secondary prophylaxis is not necessary when the patient are clinically asymptomatic and the CD4+ cell counts are above 150/microl.

The clinical data of 21 patients, suffering AIDS-related histoplasmosis, who were able to interrupt antifungal secondary prophylaxis, after achieving a partial restoration of the cell mediated immunity by HAART administration, are presented. They were 16 males and five females, whose ages varied between 32 and 54 years (mean = 38.5 years). All of them presented disseminated progressive forms of histoplasmosis, with multiple locations (skin, mucous membranes, liver, spleen, lymph nodes and lungs). The majority of the cases suffered other concomitant diseases (specially tuberculosis and Kaposi sarcoma), 66.6 % of the patients had less than 50 CD4+ cells/microl at the start of treatment and the average viral burden was 278,385 RNA copies/ml. The initial treatment consisted in 400 mg/day of itraconazole, by oral route, in 14 cases and the remaining seven patients were treated with amphotericin B, intravenously, at a daily dose of 0.7 mg/kg of body weight. One patient who did not tolerate amphotericin B and presented a partial response to itraconazole, was treated with posaconazole orally at a daily dose of 800 mg. Fourteen patients received oral itraconazole at a daily dose of 200 mg as a secondary prophylaxis, the remaining three patients were treated with intravenous amphotericin B, 50 mg twice a week. After HAART for an average lapse of 16.7 months (10 to 32 months), five cases showed CD4+ cells counts above 150 cells/microl and the remaining 16 presented more than 200 cells/microl; 18 of them had undetectable viral burden and all cases were asymptomatic. The follow up after secondary prophylaxis discontinuation varied between six months and six years (mean= 33.6 months). Twenty out of 21 patients (95 %) were clinically stable, without any manifestation of relapses, including two patients who abandoned HAART. One patient, who discontinued HAART, contracted a fatal bacterial pneumonia. Even though the limited number of cases, the data presented in this study seem to suggest that it is possible to interrupt antifungal secondary prophylaxis of histoplasmosis, when the patient is clinically asymptomatic and the CD4+ cells counts are above 150 cells/microl.

A 41-year-old woman with no known immunosuppression experienced a 12-year period of a relapsing phaeohyphomycosis. Despite administration of multiple courses of therapy with standard antifungals, sustained clinical remission was not achieved. A partial response was seen initially with the combination of itraconazole and flucytosine therapy, but the patient did not respond to subsequent treatment. During the patient's pregnancy, the mycosis became disseminated, with lymphadenopathy and fever, and was considered life threatening. Despite receipt of parenteral amphotericin B therapy, the patient did not show a clinical response. After premature delivery by cesarean section, treatment with oral posaconazole suspension (800 mg/day) was started. The patient's condition improved within 1 week after initiating treatment; therapy was continued for 13 months. During posaconazole treatment, the patient showed a complete clinical response, with negative results of fungal cultures.

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.

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.

The aim of this study was to determine the value of blood culture as a parameter of treatment effectiveness in experimental histoplasmosis. A total of thirty five hamsters, weighing approximately 120g, were inoculated intracardially with 0.1 ml of a suspension containing 4 x 10(7) cells/ml of the yeast phase of H. capsulatum. Treatments were started one week after the infection and lasted for 3 weeks. The azoles, (itraconazole, saperconazole and fluconazole) were administered once a day by gavage, at a dose of 8 mg/kg; Amphotericin B was given intraperitoneally every other day at a dose of 6mg/kg. Blood samples (1 ml) were obtained by heart punction from the 4th day after infection and were seeded in Sabouraud honey-agar and BHI-agar. The hamsters that survived were killed one week after treatment completion and the following criteria were considered for treatment evaluation: 1) rate of spontaneous death, at the end of the experience; 2) microscopic examination of Giemsa smears from liver and spleen and 3) determination of CFU in spleen cultures. Amphotericin B was the most effective drug, with negative blood cultures at day 20, negative spleen cultures in all cases and all the animals survived until the end of the study. Fluconazole was the less effective drug, blood cultures were positive during the whole experience, spleen cultures showed a similar average of CFU when compared with the control animals and 42.8% of these animals died. Saperconazole and itraconazole showed a similar activity, with survival of all hamsters and negative blood cultures at 23 and 26 days respectively. Blood culture seems to be valuable parameter for treatments' evaluation in experimental histoplasmosis of the hamster.

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.

A comparative study, using 5 antifungal drugs for the treatment of an experimental model of murine cryptococcosis, was carried out. One hundred and eighty Balb C mice, divided in 18 groups of 10 animals each, were intraperitoneally inoculated with 10(7) cells of Cryptococcus neoformans var. neoformans. Twelve groups were treated with different schedules beginning 5 days after inoculation, for 2 or 4 weeks. The treatments were the following: amphotericin B (6 mg/kg/every other day, intraperitoneally); 5-fluorocytosine (300 mg/kg/day, by gavage); amphotericin B (6 mg/kg/every other day, intraperitoneally) in association with 5-fluorocytosine (300 mg/kg/day, by gavage); fluconazole, itraconazole and Sch 39.304 (all at the daily dose of 16 mg/kg, by gavage). The six remaining groups were used as controls and received the solvent for the drugs. The evaluation of the efficacy of the different treatments was based on: survival time; macroscopy of brain, lungs, liver and spleen at autopsies; presence of encapsulated yeasts in microscopic examination of wet preparations of these organs; and cultures of a concentrated suspension of brain and lungs. In the animals treated for 2 weeks, the combination of amphotericin B + 5-fluorocytosine was the most useful; it negativized the micro and macroscopic findings as well as 90% of the cultures, and prolonged the survival time up to 60 days. Sixty per cent of the mice which received amphotericin B exhibited the same survival time and macroscopic findings as those treated with the association of amphotericin B + 5-fluorocytosine. Among the azolic compounds, Sch 39.304 proved to be the most effective in the prolongation of survival time.(ABSTRACT TRUNCATED AT 250 WORDS)

The efficacy of two triazoles, SCH 39304 and fluconazole, in the treatment of disseminated cryptococcosis in Wistar rats was determined. A total of 160 rats were inoculated intracardiacally with 2 x 10(5) cells of Cryptococcus neoformans. Both drugs were administered by gavage once daily, at three doses (8, 16, and 32 mg/kg/day). Two treatment schedules were followed: (i) treatment began 1 week after infection and continued for 3 weeks and (ii) prophylaxis treatment began 3 days before infection and continued an additional 3 weeks. Evaluation was based on (i) macroscopic examination of lungs, (ii) microscopic examination of brains and lungs, (iii) histopathology of brains and lungs, and (iv) determination of number of CFU in brains. The number of CFU was the best measure of activity. SCH 39304 was more active than fluconazole in both regimens, and, prophylactically, SCH 39304 was able to achieve biological cures.

The author presents the drugs that are available for the treatment of opportunistic mycoses: amphotericin B, nystatin, 5-fluorocytosine, miconazole and the newest imidazole derivative econazole. He presents his experience with econazole in 4 cases with deep mycoses. He speaks of the mode of application and the therapeutical limits of these products as well as of the favorable factors and the prophylactic measures to be taken.

A non-comparative open trial with itraconazole in progressive forms of human histoplasmosis was carried out. Thirty two patients who completed 6 months of treatment were included; 29 suffered the chronic disseminated form; 2 exhibited a chronic pulmonary histoplasmosis and one patient presented a subacute disseminated form. Thirty patients were males and 2 females; their ages ranged from 37 to 78 years old (average 56.9). The following underlying diseases were registered: hepatopathies: 12 cases; endocrinopathies and steroid therapy: 13 cases; chronic obstructive pulmonary disease: 10 patients; malignancies: 3 cases; long treatment with psychotropic drugs; 2 cases and 1 immunodeficiency of unknown origin. The therapeutic schedule applied was: 100 mg/day, orally, during 2 months, followed by 50 mg/day for another four months. Twenty-nine patients achieved clinical cure, two showed a striking improvement (both had the chronic pulmonary form) and the treatment could not be evaluated in 1 case. A follow-up of longer than a year was registered in 23 cases, one died as a consequence of mesothelioma and another due to renal impairment, and no relapses were observed. A decreasing complement fixation titer (of more than 2-fold) was observed in 19 cases; 8 of 10 patients with negative skin tests turned positive and the erythrocyte sedimentation rate was reduced to more than a half in 24 cases. Concerning side-effects, a mild, transient and asymptomatic rise of the hepatic enzymes was registered in 9 patients. It seems that itraconazole will be the drug of choice in the treatment of human histoplasmosis in immunocompetent patients.

329 adult patients with tinea pedis interdigitalis, which clinical diagnosis was confirmed by positive direct microscopic examinations and cultures of organisms from the lesions, were enrolled in this open and multicentric study. Informed consent was requested and obtained in each case. The bifonazole, 1% gel, tested was applied topically once daily for 3 weeks. Weekly clinical controls were performed during the treatment period and, at least, two clinical mycological posttreatment assessments were carried out. The evaluation criteria were based on the clinical and mycological findings at the end of the second posttreatment week. According to these criteria, the results obtained were: very good (clinical cure, negative mycology) 276 (84.0%); good (clinical improvement, negative mycology) 32 (9.5%); moderate (clinical improvement, positive mycology) 20 (6.0%), and failure (no clinical and mycological changes) 1 (0.5%). Tolerance was excellent, side effects were not observed in any case.

With the objectives of determining the effectiveness of bifonazole 1% powder in the prophylactic treatment of tinea pedis interdigitalis and its local tolerance, 200 patients who achieved clinical and mycological cure in another previous trial with bifonazole 1% gel, and who were also reliable in the compliance of the treatment, were included in this study. Informed consent was requested and obtained in each case. This was a multicenter, double-blind, controlled and comparative study of one group (100 patients) treated with bifonazole verum against another group (100 patients) treated with bifonazole placebo. The allocation to each group was performed by randomization. Bifonazole was applied once daily in the morning on both feet, after showering, and inside shoes; patients applied it again when changing shoes or socks during the day. Treatment lasted up to 6 months. During the treatment, patients were clinically and mycologically assessed once a month and, if it was necessary, when signs and/or symptoms of infection reappeared. The evaluation criteria were based on the reinfection, clinically and mycologically demonstrable, during the treatment. 29 patients abandoned the treatment. Reinfection was observed in 57 out of the 171 patients who finished the treatment, 47 reinfections occurred in the placebo group and the remaining 10 in the verum group. Tolerance was excellent, no side effects were observed in any patient.

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.

Sixty-one patients with superficial candidiasis, confirmed on entry by clinical examination and mycological culture, were treated with a single daily application of a 1% bifonazole gel over a period of 4 weeks. Patients were seen every week during treatment and then followed-up for 2 weeks. An overall assessment of response to treatment, based on the clinical and mycological culture findings at the 14-day follow-up visit, showed that the results were very good in 49 and moderate in 9 patients, with only 3 patients being considered as failing to respond. Local tolerance was very good, but burning was reported by 1 patient, burning and itching by 1, and ardor and irritation by one. All these side-effects occurred at the start of treatment and they subsided without interruption of bifonazole treatment.

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.

A comparative study between itraconazole, ketoconazole and amphotericin B in the treatment of experimental histoplasmosis in hamsters was carried out. Seventy five animals were inoculated intracardiacally with the yeast-phase of Histoplasma capsulatum. They were divided in 5 groups: 1) treated with itraconazole by gavage (g) at a daily dose of 16 mg/kg; 2) treated with ketoconazole by (g) at a daily dose of 80 mg/kg; 3) treated with amphotericin B intraperitoneally (i.p.) at 6 mg/kg every other day; 4) control animals receiving distilled water i.p. and 5) control animals receiving P.E.G. 200 by (g). All the treatments were started one week after the challenge inoculation and they were given for 21 days. The results were evaluated by autopsy of all the animals one week after the end of the treatments. The following determinations were taken into account: microscopic examinations of spleen, liver and lungs and cultures of the spleen with determination of colony forming units/g. All the antifungal drugs used in this study were able to cause negative microscopic examinations of the liver, spleen and lungs; but only amphotericin B produced culture negative results. Itraconazole and ketoconazole presented 66% and 86% of positive cultures respectively, nevertheless the C.F.U. were lower than those obtained in control groups. In these experimental conditions amphotericin B seems to be more active than the azolic compounds and itraconazole is slightly superior to ketoconazole at a lower dose.

One hundred and twenty-one patients with tinea (pityriasis) versicolor, confirmed by pretherapeutic clinical and mycological examination, were treated with a single daily application of bifonazole (BAY h 4502) 1% gel for 2 weeks. Weekly clinical controls were performed during the treatment period and at least two clinical and mycological post-therapeutic controls were given. Overall results were very good in 98 patients, good in 15, moderate in 7 and failure in 1 patient. Local tolerance was very good; only 1 patient presented with slight erythema and pruritus during the treatment.

An open, multicentre study was carried out in 103 patients with confirmed dermatophyte infections (tinea cruris or tinea corporis). The fungi isolated were Tr. rubrum (45), Tr. mentagrophytes (11), Ep. floccosum (26) and M. canis (21). All patients were treated with a single daily application of bifonazole (1% gel) and the duration of treatment was 3 weeks. Weekly clinical controls were performed during the therapeutic period and at least two clinical and mycological examinations were given after the end of treatment. Treatment was evaluated according to the clinical and mycological findings at the 14th post-therapeutic day. The results obtained were classified as very good in 80 patients, good in 11, moderate in 11 and failure in 1 patient. Local tolerance was very good and no side-effects were observed in any patients.

A comparative study among amphotericin B, 5-fluorocytosine, itraconazole and fluconazole in the treatment of experimental cryptococcosis in mice, was carried out. Seventy male Balb C mice were inoculated intraperitoneally with 10(7) cells of Cryptococcus neoformans var. neoformans. They were divided in 7 groups of 10 animals each one: 1) treated with fluconazole by gavage at a daily dose of 16 mg/kg; 2) treated with itraconazole by gavage at a daily dose of 16 mg/kg; 3) treated with 5-fluorocytosine by gavage at a daily dose of 300 mg/kg; 4) treated with amphotericin B intraperitoneally at a dose of 6 mg/kg every other day; 5) control animals receiving polietilenglicol 200 by gavage; 6) control animals receiving distilled water by gavage and 7) control animals receiving sterile distilled water by intraperitoneal route. All the treatments started 5 days after the challenge inoculation and they were given for 2 weeks. The following parameters were taken into account: survival time, macroscopic aspect of the organ after the complete autopsy, microscopic investigation of yeasts in brain, lungs, spleen and liver, histopathology studies of these organs, the colony forming units per gram and massive seeding of brain and lungs. The survival index of the different groups was the most efficient method to measure the antifungal compounds activity. Amphotericin B increased significantly the animals survival and modified the histopathologic response in the studied organs. The colony forming units and the massive seeding in brain and lung showed that this antifungal agent is unable of producing the biological cure of this experimental model.(ABSTRACT TRUNCATED AT 250 WORDS)