Fluconazole is associated with survival to clinical remission in 75% of dogs with blastomycosis. Although dogs receiving fluconazole were treated longer, drug costs were one-third those of itraconazole. Hepatotoxicosis, as estimated by increases in serum ALT activity, can be observed with similar incidence for both drugs.
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ABPA was mostly misdiagnosed as tuberculosis. Wheeze is present in almost all patients with ABPA, which can be useful in differentiation from tuberculosis. Obstructive ventilatory defect, peripheral blood eosinophilia, fleeting pulmonary infiltration and central bronchiectasis were features of ABPA. Measurement of total IgE, A.fumigatus-specific IgE levels and immediate cutaneous reaction to A.fumigatus are helpful for confirmation of the diagnosis.
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This study was performed to investigate (i). the clinical, histopathological and biochemical changes in quails (Coturnix coturnix japonica) with experimentally induced aspergillosis; and (ii). the efficiency of itraconazole treatment on these infected birds. A total of 18021-day-old male quails was randomly divided into three groups (control, infected untreated and infected treated), each containing 60. The experimental infection was set by intratracheal inoculation of 0.2 ml inoculum of Aspergillus fumigatus (CBS 113.26 strain) consisting of approximately 2.7 x 106 spores/ml. Two days after the inoculation, general clinical signs of aspergillosis in the respiratory tract were observed. In the histopathological examination, caseous foci were found in lungs, trachea and on airsacs. All quails died in the infected untreated group. Aspergillus fumigatus was isolated from the various organs of all dead quails. There was no significant change in serum aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) activities in infected untreated birds compared with controls. However, alanine aminotransferase (ALT) activity, albumin and calcium levels, and albumin/globulin (A/G) ratio were lower while phosphorus and globulin levels were higher in the infected untreated group than in controls. Each quail in the infected treated group was given 10 mg/kg/day itraconazole via drinking water for 7 days immediately after the first clinical findings. Although all quails died in the infected untreated group, 41 quails survived in the itraconazole treatment group. Biochemical values also returned approximately to the control levels after the treatment. The conclusion was drawn that aspergillosis in the quails might cause economical losses because of high mortality. Oral itraconazole treatment of aspergillosis might lower the mortality rate in quails.
We report a case of disseminated histoplasmosis in a 33-year old Ecuadorian patient with AIDS and a CD4 lymphocyte count of 39 cells/microl. He presented with prolonged fever and cough, was diagnosed with hemophagocytic syndrome and multiple organ failure and died 18 days after admission. Histoplasma capsulatum was isolated post-mortem from bone marrow biopsy and blood culture. In a literature review we found 22 published cases of disseminated histoplasmosis in patients with AIDS in Spain since 1988. All but two were men under 50 years old. Nineteen had been born or had lived in endemic areas. The diagnosis of histoplasmosis was established by culture of bone marrow biopsy in 10 cases. Itraconazole was introduced as a second drug after amphotericin B in ten of the thirteen patients who survived.
Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials.
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Paracoccidioidomycosis (PCM) is a systemic granulomatous human mycosis caused by fungi of the genus Paracoccidioides, which is geographically restricted to Latin America. Inhalation of spores, the infectious particles of the fungus, is a common route of infection. The PCM treatment of choice is azoles such as itraconazole, but sulfonamides and amphotericin B are used in some cases despite their toxicity to mammalian cells. The current availability of treatments highlights the need to identify and characterize novel targets for antifungal treatment of PCM as well as the need to search for new antifungal compounds obtained from natural sources or by chemical synthesis. To this end, we evaluated the antifungal activity of a camphene thiosemicarbazide derivative (TSC-C) compound on Paracoccidioides yeast. To determine the response of Paracoccidioides spp. to TSC-C, we analyzed the transcriptional profile of the fungus after 8 h of contact with the compound. The results demonstrate that Paracoccidioides lutzii induced the expression of genes related to metabolism; cell cycle and DNA processing; biogenesis of cellular components; cell transduction/signal; cell rescue, defense and virulence; cellular transport, transport facilities and transport routes; energy; protein synthesis; protein fate; transcription; and other proteins without classification. Additionally, we observed intensely inhibited genes related to protein synthesis. Analysis by fluorescence microscopy and flow cytometry revealed that the compound induced the production of reactive oxygen species. Using an isolate with down-regulated SOD1 gene expression (SOD1-aRNA), we sought to determine the function of this gene in the defense of Paracoccidioides yeast cells against the compound. Mutant cells were more susceptible to TSC-C, demonstrating the importance of this gene in response to the compound. The results presented herein suggest that TSC-C is a promising candidate for PCM treatment.
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We report a case of severe tinea capitis, treated successfully with griseofulvin. In our opinion, the treatment of this severe dermatophytosis with griseofulvin is safe and effective. Other treatments, such as itraconazole pulsed therapy, failed, despite an initial improvement, leading to an aggressive recurrence of the lesion. We chose griseofulvin for its well-known large spectrum activity, also against uncommon species, like Microsporum Gypseum, which are responsible for the most severe cases.
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Fluconazole and itraconazole are two investigational triazole antifungal agents that are currently undergoing clinical trials in the United States. Both are active orally, have favorable pharmacokinetics (i.e., good bioavailability, long half-life, low plasma protein binding), and possess activity against several systemic fungal pathogens. In addition, preliminary information suggests that these agents are substantially less toxic than currently available azole compounds. Fluconazole and, to a lesser degree, itraconazole have been shown to be highly effective for the treatment of cryptococcal meningitis. The potential for drug interactions is much lower with these agents compared to drugs such as ketoconazole.
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Abnormally viscous bronchial secretions, a characteristic feature of cystic fibrosis (CF), may trap bacteria and fungi, allowing transient or chronic lung colonization. We report here a case of persistent Scedosporium apiospermum colonization in a patient with CF, who subsequently developed a lung mycetoma, and died with neurological symptoms suggestive of cerebral fungal involvement. Six isolates from consecutive sputum samples were molecularly typed by random amplification of polymorphic DNA (RAPD) using primers UBC701, UBC703, and GC70. Moreover, in vitro susceptibility of these isolates to current antifungals (amphotericin B, itraconazole, voriconazole, posaconazole, caspofungin and anidulafungin) was investigated by means of both E-test and CLSI methods. Antifungal susceptibility testing showed low minimum inhibitory concentration values only for triazole drugs. However, a unique genotype was isolated over a 12-month period, despite antifungal treatment with voriconazole for three months. This case report illustrates the therapy-refractory feature of this fungus, and provides new evidence that, as already reported, once a genotype of S. apiospermum has established colonization, it seems not to be replaced by others.
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Itraconazole was administered orally to two patients with sporotrichosis, 10 patients with paracoccidioidomycosis, three with mycetomas (due to Madurella grisea, Streptomyces madurae, and Pseudochaetosphaeronema larense, respectively), nine with chromomycosis due to Cladosporium carrionii, five with chromomycosis due to Fonsecaea pedrosoi and five with leishmaniasis (including one with the nodular disseminated form). The clinical and laboratory tests showed excellent tolerance to the drug with a total absence of adverse reactions. Satisfactory results were achieved against paracoccidioidomycosis, sporotrichosis, and chromomycosis due to C. carrionii (apparent cure was achieved in a short time). Encouraging improvement was noted in the treatment of mycetoma due to M. grisea. Among the five cases of leishmaniasis, a complete clearing was achieved in one and an encouraging improvement in two, including the one with the nodular disseminated form. Two patients with F. pedrosoi infection were apparently cured after the addition of thermotherapy and flucytosine, respectively, to the treatment regimen.
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During the years 1999-2002, we obtained information from the 'Health Search Database', (HSD) an Italian general practice research database. Among a total sample of 457 672 eligible patients, we included those aged >16 years, and whose diagnoses could be classified as mycosis. Itraconazole and fluconazole users were then selected. A potentially drug-drug interaction (DDI) occurred when the use of concomitant drugs were recorded within +/-30 days from the date of the first azoles prescription. Interacting drugs were classified according to the summary of product characteristics (SPC) as provided by the Italian Pharmaceutical Repertory (REFI).
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Design, synthesis and activity study of novel antifungal triazoles.
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Of the 64 patients, 48 (75%) had symptoms suggestive of septicemia and 16 had no symptoms suggestive of septicemia. No antifungal therapy was given to asymptomatic patients; they recovered from candidemia without development of any sequelae. Of the 48 symptomatic patients 11 died before results of fungal culture became available and antifungal therapy could be started. Thirty seven patients were treated with itraconazole (10 mg/kg/day orally or through gastric tube). Seven (18.9 %) of 37 patients died, 3 within first week of antifungal therapy. Thirty (81%) patients recovered; microbiological cure was noted on average by day 14 (range 4-30 days). The mean +/- SD duration of therapy in patients who responded was 24 +/-7 days (range 21-42 days). None had any major side effect.
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Itraconazole (ITZ) microflakes were produced by supercritical antisolvent (SAS) method and simultaneously mixed with pharmaceutical excipients in a single step to prevent drug agglomeration. Simultaneous ITZ particle formation and mixing with fast-flo lactose (FFL) was performed in a high-pressure stirred vessel at 116 bar and 40 °C by the SAS-drug excipient mixing (SAS-DEM) method. The effects of stabilizers, such as sodium dodecyl sulfate and poloxamer 407 (PLX), on particle formation and drug dissolution were studied. Drug-excipient formulations were characterized for surface morphology, crystallinity, drug-excipient interactions, drug content uniformity, and drug dissolution rate. Mixture of drug microflakes and FFL formed by the SAS-DEM process shows that the process was successful in overcoming drug-drug agglomeration. PLX produced crystalline drug flakes in loose agglomerates with superior dissolution and flow properties even at higher drug loadings. Characterization studies confirmed the crystallinity of the drug and absence of chemical interactions during the SAS process. The dissolution of ITZ was substantially higher due to SAS and SAS-DEM processes; this improvement can be attributed to the microflake particle structures, effective deagglomeration, and wetting of the drug flakes with the excipients.
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Itraconazole is not only an effective and safe therapy for controlling exacerbations of SD but may also be used as maintenance therapy to prevent disease recurrence.
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The incidence of systemic fungal infections has risen, as shown by increases in the numbers of immunosuppressed or immunocompromised patients. The consequences of these fungal infections are occasionally serious. However, the efficacy of antifungal prophylaxis in patients receiving corticosteroid treatment has not been well investigated, even though they are susceptible to severe fungal infections. Therefore, we retrospectively evaluated the prophylactic efficacy of an antifungal agent-oral itraconazole solution (ITCZ-OS)-for immunosuppressed patients receiving corticosteroids in a single institution. Of 39 patients, 18 received prophylaxis with ITCZ-OS at a dose of 200 mg/day, and 21 did not. As a result, no fungal infections developed in the prophylactic group, but 7 of the 21 patients (33%) in the non-prophylactic group suffered from fungal infections consisting of 3 non-invasive candidiases, 2 invasive candidiases, and 2 invasive pulmonary aspergilloses. Among the non-prophylactic group, aging and hypoalbuminemia were statistically significantly associated with incidence of invasive fungal infections. Of the four patients with invasive fungal infections, three had concomitant chronic illness such as diabetes. Toxicity among the prophylactic group was not statistically significantly different from that of the non-prophylactic group. In addition, none needed discontinuation of the drug. These results indicate the potential antifungal prophylactic effect of ITCZ-OS for a subset of patients treated with moderate or high doses of corticosteroids.
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A 32-year-old immunocompetent female presented with sensory aphasia and psychomotor seizure due to aspergillosis in the left temporal lobe spreaded from the left orbita. In spite of oral administration of itraconazole, the symptoms continued to deteriorate due to extension of the lesion to the left temporoparietal white matter. As a result of the stereotactic biopsy of the lesion, she was histologically diagnosed as intracerebral aspergillosis. Intravenous administration of fluconazole and amphotericin B was apparently effective for the lesion, and the symptoms subsided. Ga-67 scintigram could serve as useful adjuncts to magnetic resonance images for evaluation of the therapy. This case is unusual in that an immunocompetent patient suffered from the intracerebral aspergillosis, which invasively spreaded into the parenchyma. We discussed about her pathology, diagnosis, therapy and the route of invasive aspergillosis to the parenchyma.
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Voriconazole was more active in vitro than amphotericin B and itraconazole, with 95.6% (65/68) of strains exhibiting MICs of < or = 2 mg/l. A. flavus, A. versicolor, A. terreus, A. ochraceus, A. sclerotiorum, A. ustus and A. reptans species presented reduced susceptibility to amphotericin B (MIC > or = 2 mg/l); A. niger, A. versicolor, A. sclerotiorum and A. ustus showed in vitro resistance to itraconazole (MIC > or = 1 mg/l); and A. sclerotiorum and A. ustus displayed poor susceptibility to voriconazole (MIC > or = 2 mg/l).
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Mean age of patients was 59 years, and 45% were female. Overall, patients with CPA had substantial health status impairment at baseline. After treatment, 47%-50% gained substantial health improvement with a mean reduction of score of 14 at both 6 and 12 months, whereas 32% deteriorated with a mean rise of score of 11 and 14 after 6 and 12 months of treatment and observation, respectively, and 21% were not much different (stable). Patients gained therapeutic benefit irrespective of their illness severity where >50% of those who had "poor" and "very poor" status at baseline improved with score reduction of ≥4 after 6 months of treatment. Replicating this analysis using a health status category, we found that at least 50% of patients with a "poor/very poor" health status category at baseline improved significantly to "fair" or "good/very good" categories. Side effects burdened health status considerably. In multivariate analysis, dyspnea and disease severity significantly defined health status impairment.
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Currently, price-controlled antifungal drugs are less commonly used by practitioners. Although the dermatologists favor price control, the initiative undertaken by the Government has not reached them. This shows the need to bridge the gap between policy makers and health-care service providers to help the ailing population.