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In patients with Trichophyton rubrum infections, refractory to itraconazole treatment, altered drug absorption or drug interactions has to be considered. Careful monitoring and adjustment of itraconazole is of vital importance.
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Fifty-seven samples of 54 diabetics and 50 samples of 50 controls grew dermatophytes. In both groups, Trichophyton rubrum was the most common isolate. Mean MIC values of terbinafine, itraconazole, and fluconazole for all of the isolated dermatophyte strains were similar in two groups (P>0.05). The difference in mean MIC values of three antifungals for T. rubrum and T. mentagrophytes between two groups was not statistically significant (P>0.05).
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A prospective, randomized, double-blind, placebo-controlled, restricted sequential design trial was performed in 71 adults undergoing orthotopic liver transplantation. Patients were randomly assigned to receive either itraconazole (5.0 mg/kg orally, preoperatively, 2.5 mg/kg orally, two times a day, postoperatively) or placebo. Therapy continued for a maximum of 56 days or until patient was discharged from hospital or met a predefined endpoint. Measurements included incidence of fungal colonization, superficial or systemic fungal infections requiring systemic therapy, adverse events, and mortality rate.
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Embedding ITZ NP in inhalable microparticles is a very effective method to produce DPI formulations with optimal aerodynamic properties and enhanced ITZ solubility. These formulations could be applied to other poorly water-soluble drugs and could be a very effective alternative for treating invasive pulmonary aspergillosis.
The combined effects of lysozyme and various antifungal agents were investigated by microbroth dilution method against Candida albicans in vitro. Synergistic anti-Candida activity was observed between egg white lysozyme and itraconazole, clotrimazole, miconazole and lanoconazole. Similar, although not as clear, combination anti-Candida activities were seen in the cases of ketoconazole, bifonazole, amphotericin B and nystatin. Anti-Candida activity of fluconazole was not affected by the addition of lysozyme, however. Physiological roles of this combination effect in anti-Candida therapy by azole antifungals were discussed.
A rare case of pyoderma gangraenosum caused by Rhizopus arrhizus is reported. The patient, a 50-year-old male farmer, was admitted to hospital complaining of gangrening and festering of the right upper arm with severe pain for nearly 2 months. A lesion was found on the inside of right upper arm. The central skin part of the lesion became black dry gangrenous, the periphery was deeply ulcerated with yellow-green pus. The necrotic crust, biceps, triceps and vessels inherited a histopathologically proven fungal infection. The fungus isolated was identified as Rhizopus arrhizus. The infection was successfully treated with itraconazole.
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A 7-year-old female-spayed, domestic short-haired cat was presented to her veterinarian with a mass on the hind paw. Histopathologic examination of a tissue biopsy revealed nodular pyogranulomatous panniculitis with intralesional pigmented fungal hyphae. A dematiaceous fungal isolate was isolated with a micromorphological phenotype consistent with the anamorphic genus Exophiala: budding cells, torulose mycelium and annellidic conidiogenesis from simple conidiophores consisting of terminal and lateral cells that tapered to a short beak at the apex. Sequence homology of the internal transcribed spacer region of the rDNA gene confirmed the identification of the isolate as Exophiala attenuata. Reported here is the first confirmed case of feline phaeohyphomycosis caused by E. attenuata in North America. Similar to historical cases of feline phaeohyphomycosis caused by Exophiala spp., there was no history or postmortem evidence to suggest the patient was in an immunocompromised state (e.g., suffering from FeLV or FIV). Although aggressive surgical excision of local lesions is recommended prior to drug treatment when dealing with subcutaneous phaeohyphomycosis, surgery followed by itraconazole treatment did not resolve the E. attenuata infection in this cat.
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Measurement of Blastomyces antigen in urine or serum by the MVista Blastomyces antigen EIA is more sensitive than measurement of anti-Blastomyces antibodies for diagnosis of blastomycosis in dogs.
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The evaluation of susceptibility patterns of clinical and laboratory isolates of dermatophytes and Candida to sertaconazole nitrate has been determined using macrodilution and microdilution test methods in laboratories worldwide. Antimycotics that have been compared to sertaconazole nitrate include itraconazole, clotrimazole, miconazole, and terbinafine. A comparison of the minimum inhibitory concentrations clearly shows differences in potency and spectrum among the various agents. This article reviews the antifungal activity of sertaconazole nitrate against major fungal pathogens that cause and complicate tinea pedis. In light of the new topical formulation of sertaconazole nitrate, this compilation of data from the literature is helpful for relating in vitro data to the tissue concentrations required for effective eradication of cutaneous fungal infections.
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A 75-year-old man was admitted with bloody sputum. His chest radiogram and CT revealed a fungus ball within a cavity lesion of the right upper lung field. Aspergillus fumigatus was cultured from bronchoalveolar lavage fluid. He was treated with itraconazole (ITCZ) and micafungin (MCFG), but his fungus ball increased. One year after initiating voriconazole (VRCZ) therapy. After 1 year, the fungus ball had significantly reduced, with no significant adverse events. This case suggests that administration of VRCZ can be recommended for pulmonary aspergilloma of responding poorly to other antifungal agents.
In this paper, a cutaneous alternariosis is described. This is a strange opportunist infection with less than 100 cases. The patient was not VIH although inmunocompromised due to several factors: Malabsorption Syndrome, megaloblastic anemia secondary to gastrectomy and distal pancreatomy with gastrodigiunostomia due to gastric adenocarcinoma four years ago; splenectomied in the same operation, long treatment with hydantoin, and corticosteroids. The patient was managed in the internal medicine unit due to a problematic respiratory infection with cardiac rhythm disorder and progressive debility in lower limbs, together with cutaneous lesions in which "alternaria sp" was isolated by culture. After beginning treatment with oral itraconazole, his evolution was excellent. The main interest consists in the rareness and the original presentation of the cutaneous alternariosis in this case.
Itraconazole is often given for fungal prophylaxis to lung transplant recipients after transplantation. The aim of this study was to determine the extent of interaction between tacrolimus and itraconazole in lung transplant recipients and the efficacy of itraconazole prophylaxis.
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MK-0991 (formerly L-743,872) is a water soluble semisynthetic echinocandin that possess potent, broad-spectrum antifungal activity. We evaluated the in vitro activity of MK-0991 and an echinocandin derivative LY303366, compared with that of itraconazole, fluconazole, amphotericin B and 5-flucytosine against 400 blood stream isolates of Candida spp. (nine species) obtained from more than 30 different medical centers. MICs for all antifungal drugs were determined by the NCCLS method using RPMI 1640 test medium. Both MK-0991 and LY303366 were very active against all Candida spp. isolates (MIC90, 0.25 and 1 microgram/mL, respectively). MK-0991 was two-fold to 256-fold more active than amphotericin B, fluconazole, itraconazole (except against C. parapsilosis), and 5-flucytosine (except against C. glabrata and C. parapsilosis). LY303366 was comparable to MK-0991, but was fourfold less active against C. tropicalis (MIC90, 0.5 versus 0.12 microgram/mL) and C. parapsilosis (MIC90, > 2 versus 1 microgram/mL). All of the isolates for which fluconazole and itraconazole had elevated MICs (> or = 64 micrograms/mL and > or = 1 microgram/mL, respectively) were inhibited by < or = 0.5 microgram/mL of MK-0991 and LY303366. These results suggest both MK-0991 and LY303366 possess promising antifungal activity and further in vitro and in vivo investigations are warranted.
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We determined the in vitro susceptibilities of 314 strains of Candida spp., representing 13 species rarely isolated from blood, to posaconazole and voriconazole as well as four licensed systemic antifungal agents (amphotericin B, flucytosine, fluconazole, and itraconazole). The organisms included 153 isolates of C. krusei, 67 isolates of C. lusitaniae, 48 isolates of C. guilliermondii, 10 isolates of C. famata, 10 isolates of C. kefyr, 6 isolates of C. pelliculosa, 5 isolates of C. rugosa, 4 isolates of C. lipolytica, 3 isolates of C. dubliniensis, 3 isolates of C. inconspicua, 2 isolates of C. sake, and 1 isolate each of C. lambica, C. norvegensis, and C. zeylanoides. MIC determinations were made by the National Committee for Clinical Laboratory Standards reference broth microdilution method and Etest (amphotericin B). Resistance to both amphotericin B and fluconazole was observed in strains of C. krusei, C. lusitaniae, C. guilliermondii, C. inconspicua, and C. sake. Resistance to amphotericin B, but not to fluconazole, was also observed among isolates of C. kefyr and C. rugosa. Posaconazole and voriconazole were active (MIC, < or = 1 micro g/ml) against 94 to 100% of these isolates. In contrast to the more common species of Candida causing bloodstream infection, these rare species appear to be less susceptible to the currently licensed systemic antifungal agents, with the exception of voriconazole. Continued surveillance will be necessary to detect the emergence of these species as more prevalent, resistant pathogens. The new triazoles appear to offer acceptable coverage of uncommon Candida sp. bloodstream infections.
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In 1993, the Netherlands Centre for Monitoring of Adverse Reactions to Drugs received 1585 reports of suspected adverse reactions. The most important reports concerned myocardial infarction due to sumatriptan, cholestatic hepatitis due to itraconazole, agranulocytosis due to trazodone and bleeding due to fluoxetine and fluvoxamine. Other published reports concerned cholestatic hepatitis due to amoxicillin/clavulanic acid, hair loss due to beta-blockers, muscle necrosis due to diclofenac, bronchospasm, apnoea and cardiac arrest due to dipyridamole perfusion scintigraphy, interaction of fluvoxamine/fluoxetine and coumarins, liver enzyme elevations due to heparin, skin reactions due to Imedeen, deafness due to neomycin, addiction to nicotine chewing gum, atrial fibrillation and skin reactions due to nicotine patches, interaction between oral contraceptives and terbinafine, neonatal problems caused by psychopharmacological agents, parapemphigus caused by sulfasalazine, taste loss due to terbinafine en intracranial bleeding after use of tranylcypromine and beer. Pharmacoepidemiological studies were performed concerning methods for record linkage, the communication process with respect to the acitretin alert and the adverse events due to sumatriptan.
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Atak-S type fertilized eggs obtained from the Poultry Institution were used. The eggs were kept under 37 °C at 85-90% relative humidity throughout the experiment. Amphotericin B was prepared in two different concentrations (AmB 125 μg/1 mL and 0.125 μg/1 mL). The CAMs treated with sterile distilled water was specified as controls. About 0.1 mL of each containing 12.5 and 0.0125 µg of AmB, respectively, were dropped to CAM surface. Thirteen eggs were used for each group. The results were evaluated at the 48th hour of the administration of the drugs and recorded by digital camera.
The aim of the present study was to evaluate the in vitro antifungal susceptibilities of the following six antifungal drugs against clinical C. glabrata strains: amphotericin B (AmB), ketoconazole (KTZ), fluconazole (FCZ), itraconazole (ITZ), voriconazole (VCZ), and caspofungin (CASP).
Among Toll-deficient (Tl(-/-)) and wild-type fruit flies, infection with Zygomycetes isolates that had been exposed to voriconazole yielded significantly lower survival rates than infection with Zygomycetes strains grown in drug-free media. In contrast, exposure of Rhizopus oryzae to itraconazole, amphotericin B, or caspofungin and exposure of Aspergillus fumigatus to voriconazole did not alter the virulence of these isolates in fruit flies. In the murine model, infection with a R. oryzae strain preexposed to voriconazole was associated with decreased survival rates and increased pulmonary fungal burdens, compared with infection with a voriconazole-nonexposed R. oryzae strain. In addition, enhanced angioinvasion, inflammation, and expression of genes involved in stress response and tissue repair were found in mouse lungs infected with voriconazole-exposed R. oryzae.
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Of the three antifungals tested, terbinafine had the most potent in vitro antifungal activity against dermatophytes. Antifungal susceptibility tests would be useful to screen antifungal-resistant dermatophyte strains.
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The in vitro activities of amphotericin B, flucytosine, fluconazole, itraconazole, and voriconazole against 23 isolates of Geotrichum capitatum were determined by the National Committee for Clinical Laboratory Standards (NCCLS) M27-A2 microdilution method and the Sensititre and agar diffusion methods. Amphotericin B and voriconazole appeared to be the more active drugs. Sensititre showed the highest rates of agreement with the NCCLS M27-A2 method.
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The specimen collection was carried out from fungal keratitis patients attending Aravind eye hospital and Post-graduate institute of ophthalmology, Coimbatore, India and was subsequently processed for the isolation of fungi. The dilutions of antifungal drugs were prepared in RPMI 1640 medium. Minimum inhibitory concentrations (MICs) were determined and MIC50 and MIC90 were calculated for each drug tested.
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Multiple mutations in ERG11 are required to confer decreased susceptibility to posaconazole.
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Pulmonary aspergillosis was detected a median of 25 months after the diagnosis of AIDS, usually following corticosteroid use, neutropenia, pneumonia due to other pathogens, marijuana smoking, or the use of broad-spectrum antibiotics. Two major patterns of disease were observed: invasive aspergillosis (in 10 patients) and obstructing bronchial aspergillosis (in 3). Cough and fever, the most common symptoms, tended to be insidious in onset in patients with invasive disease (median duration, 1.3 months before diagnosis). Breathlessness, cough, and chest pain predominated in the three patients with obstructing bronchial aspergillosis, who coughed up fungal casts. Radiologic patterns included upper-lobe cavitary disease (sometimes mistaken for tuberculosis), nodules, pleural-based lesions, and diffuse infiltrates, usually of the lower lobe. Transbronchial biopsies were usually negative, but positive cultures were obtained from bronchoalveolar-lavage fluid or percutaneous aspirates. Dissemination to other organs occurred in at least two patients, and direct invasion of extrapulmonary sites was seen in two others. The results of treatment with amphotericin B, itraconazole, or both were variable. Ten of the patients died a median of 3 months after the diagnosis (range, 0 to 12 months).
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Paracoccidioidomycosis is one of the most prevalent systemic fungal infections in Latin American countries. The incidence rate has been increasing and its detection has gotten increasingly common in travelers or immigrants from endemic areas. It is characterized by respiratory symptoms, lymphadenopathies and skin lesions, which gradually progress and subsequently lead to death in some untreated chronic disease cases.
We report a case of Aspergillus flavus endocarditis in a 6-year-old boy with stage IV neuroblastoma with no pre-existing cardiac disease. The infection was successfully treated with high-dose liposomal amphotericin (AmBisome) once daily. Recurrence was prevented with itraconazole oral solution once daily as maintenance therapy. Adjunctive surgery was not required. The patient's cardiac function was uncompromised, but subsequent death from progressive neuroblastoma prevented long-term follow-up.
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Candida bloodstream isolates (n = 2,000) from two multicenter clinical trials carried out by the National Institute of Allergy and Infectious Diseases Mycoses Study Group between 1995 and 1999 were tested against amphotericin B (AMB), flucytosine (5FC), fluconazole (FLU), itraconazole (ITR), voriconazole (VOR), posaconazole (POS), caspofungin (CFG), micafungin (MFG), and anidulafungin (AFG) using the NCCLS M27-A2 microdilution method. All drugs were tested in the NCCLS-specified RPMI 1640 medium except for AMB, which was tested in antibiotic medium 3. A sample of isolates was also tested in RPMI 1640 supplemented to 2% glucose and by using the diluent polyethylene glycol (PEG) in lieu of dimethyl sulfoxide for those drugs insoluble in water. Glucose supplementation tended to elevate the MIC, whereas using PEG tended to decrease the MIC. Trailing growth occurred frequently with azoles. Isolates were generally susceptible to AMB, 5FC, and FLU. Rates of resistance to ITR approached 20%. Although no established interpretative breakpoints are available for the candins (CFG, MFG, and AFG) and the new azoles (VOR and POS), they all exhibited excellent antifungal activity, even for those strains resistant to the other aforementioned agents.
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The susceptibility of 30 clinical isolates belonging to six different species of filamentous fungi (Aspergillus fumigatus, Aspergillus flavus, Scedosporium prolificans, Scedosporium apiospermum, Fusarium solani, and Fusarium oxysporum) was tested against six antifungal drugs (miconazole, voriconazole, itraconazole, UR9825, terbinafine, and amphotericin B) with the microdilution method recommended by the National Committee for Clinical Laboratory Standards (NCCLS) (M38-P). The MICs were compared with the MICs obtained by a colorimetric method measuring the reduction of the dye 3-(4,5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) to formazan by viable fungi. The levels of agreement between the two methods were 96 and 92% for MIC-0 (clear wells) and MIC-1 (75% growth reduction), respectively. The levels of agreement were always higher for Aspergillus spp. (97% +/- 2.5%), followed by Scedosporium spp. (87% +/- 10.3%) and Fusarium spp. (78% +/- 7.8%). The NCCLS method was more reproducible than the MTT method: 98 versus 95% for MIC-0 and 97 versus 90% for MIC-1. However, the percentage of hyphal growth as determined visually by the NCCLS method showed several discrepancies when they were compared with the percentages of MTT reduction. A new simplified assay that incorporates the dye MTT with the initial inoculum and in which the fungi are incubated with the dye for 48 h or more was developed, showing comparable levels of agreement and reproducibility with the other two methods. Furthermore, the new assay was easier to perform and more sensitive than the MTT method.
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We describe a possible imported case of osteo-articular coccidioidomycosis in India. Culture of the computed tomography-guided aspirate revealed the growth of Coccidioides spp., which was identified as Coccidioides posadasii by sequencing of the internal transcribed spacer (ITS) region of rDNA. He was successfully treated with amphotericin B followed by itraconazole. All the previous published reports of coccidioidomycosis cases diagnosed in India are also reviewed in order to increase the awareness of this disease in non-endemic areas.
The successful use of recombinant activated factor VII (rFVIIa), in treating massive, life-threatening haemoptysis in a 55-year-old male patient with chronic necrotising aspergillosis, is reported. Patient diagnosed with chronic necrotising aspergillosis three months ago was admitted to our department with massive haemoptysis. Patient was treated as outpatient with itraconazole. One day post-admission, two doses of rFVIIa (30 microg x kg(-1)) were administered and the haemoptysis was successfully resolved. Two further doses of rFVIIa (30 microg x kg(-1) were given the following day, and after that there were no more recurrences of pulmonary haemorrhage. No thromboembolic or other adverse events were observed following rFVIIa therapy. Our findings suggest that use of rFVIIa may represent a safe and effective treatment choice for patients with haemoptysis due to aspergillosis.
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National governments without access to antifungal drugs should address this health system deficiency urgently to improve clinical outcomes from serious fungal disease. The variability in the price of antifungals between countries is striking.