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The activity of the new triazole antifungal D0870 was compared with those of itraconazole and fluconazole against Candida krusei and Aspergillus fumigatus, two fungi showing inherent tolerance of fluconazole. The activity of D0870 resembled that of itraconazole against whole cells of C. krusei, but it was less effective against A. fumigatus. However, the effect on sterol biosynthesis, in terms of the sterol type accumulating and IC50 for in-vitro biosynthesis, appeared similar in both species. The superior antifungal effect of D0870 over fluconazole appeared related to better inhibition of ergosterol biosynthesis in A. fumigatus, but in C. krusei this did not account for the entire difference which may result mainly from reduced efflux of drug.
We present four cases of cerebral amebae infection treated at our neurosurgical department. Patient 1 was a 12-year-old male with skin lesions of 2 years' progression involving the midface. He received a corticosteroid course, and, after that, he presented a right body hemiparesis. Patient 2 was a 5-year-old male, with a past surgical history of fibula fracture and osteomyelitis of 1-year evolution, associated with lesions of the surrounding skin that presented with partial seizures. Patient 3 was a 3-year-old female who presented with a stroke-like episode and with partial seizures. Patient 4 was a 6-year-old male who had ulcerative lesions in the face of 1-year evolution. After a corticosteroid course, he presented with right-body hemiparesis. All patients were human immunodeficiency virus-negative and died 1 month or less after surgery because of progressive evolution of the disease. Histopathology revealed granulomatous amebic encephalitis. All patients revealed infection from Balamuthia mandrillaris (Leptomyxiidae). Treatment consisting of pentamidine, clarithromycin, fluconazole, and 5-fluorocytosine was ineffective. Although extremely uncommon, granulomatous amebic encephalitis should be considered in the differential diagnosis of cerebral lesions while nonspecific, associated granulomatous skin lesions support the diagnosis of amebiasis.
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Amphotericin B, itraconazole, voriconazole and ravuconazole exhibited a potent activity with geometric mean (GM) MICs under 0.26 mg/L. The GM MIC of flucytosine was 7.33 mg/L and that of fluconazole was 4.16 mg/L. The rates of antifungal resistance were 5.3% for amphotericin B, 0.9% for voriconazole and 3.1% for ravuconazole. Fifteen point eight per cent of strains had itraconazole MICs > or = 1 mg/L, and 46% of strains had flucytosine MICs > or = 8 mg/L. Fluconazole susceptibility (MIC < or = 8 mg/L) stood at 53.4%.
Study on the early diagnosis, antifungal therapy, and prophylaxis for fungemia.
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There were 52 allo-HSCT recipients, two of whom were younger than 18 years of age. Twelve cases received posaconazole and 40 cases received fluconazole as primary antifungal prophylaxis. The two groups had similar transplant characteristics, conditioning, and GVHD prophylaxis regimens. The fluconazole group had a higher risk for development of invasive fungal infections within 90 days after allo-HSCT (43% vs. 8.3%, p = 0.039). Kaplan-Meier analysis indicated that the cumulative incidence of invasive fungal infection for 90 days after allo-HSCT was higher in the fluconazole group (log rank test, p = 0.047). Early discontinuation of antifungal prophylaxis for intolerance was significantly lower in the posaconazole group (8.3% vs. 50%, p = 0.017). Both groups had similar rates of impaired liver function.
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Fungal infection of the nail as well as nail bed is termed as 'onychomycosis'. It is caused by dermatophytes, non-dermatophytic fungal species and yeasts like Candida albicans. It is traditionally treated by topical antifungals, systemic agents like ketoconazole, griseofulvin, itraconazole, fluconazole, etc. Chemical avulsion or surgical removal of nail can also be tried to treat this disease. In spite of all these treatment options available, podiatrists were always in search of an ideal drug molecule with lesser side effects and which may improve the patient compliance. This exhaustive search led to the discovery of a better antifungal agent, known as "Tavaborole." A systematic literature search was carried out using databases such as PubMed, Cochrane Reviews, Google Scholar, etc. Detailed information about onychomycosis and tavaborole was gathered. Tavaborole is the first oxaborole antifungal agent approved by FDA in July 2014. It is marketed under the trade name "Kerydin." It acts by inhibiting protein synthesis in the fungus. It inhibits an enzyme known as cytosolic leucyl-transfer RNA synthetase, or LeuRS, which plays a key role in fungal essential protein synthesis. Dermatitis at the site of topical application, erythema, exfoliation and ingrowing toe nail has been reported in 1% of subjects. Tavaborole may offer a promising role in the treatment of onychomycosis and may compell podiatrists to offer its use in onychomycosis. The present study describes about chemical nature, mechanism of action and two completed phase 3 clinical trial findings of Tavaborole.
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Results from a cross-sectional observational study on candidemia conducted at Hospital de Clínicas, Federal University of Paraná, are presented. From January 2001 to December 2004, one hundred candidemia cases were evaluated. The incidence was 1.27 episodes per 1,000 hospitalizations and Candida was the eighth most frequently isolated agent from bloodstream infections. The patients ages ranged from five days to 89 years, with a mean of 32 years. Sixty percent of the cases occurred in adults (66% > 50 years old) and 40% in children (52% < one year old). Fifty-nine percent had been admitted to medical wards and 41% to the intensive care unit. Candida albicans was the most (59%) frequent species followed by Candida tropicalis (15%) and Candida parapsilosis (9%). The most (97%) prevalent coexisting conditions were the use of antibacterial drugs, central venous catheter (77%), H2 blockers (57%), total parenteral nutrition (49%) and admission to the intensive care unit (41%). Out of the 51 isolates tested, three of Candida glabrata presented dose-dependent susceptibility to fluconazole and resistance to itraconazole. One sample of Candida krusei presented dose-dependent susceptibility to fluconazole and one of Candida pelliculosa presented dose-dependent susceptibility to itraconazole. Among the study population, 68% received antifungal therapy, but the mortality was 56%.
At least one episode of candidaemia was diagnosed among 20 of 851 persons admitted during the study period. Isolates in bloodstream infection were Candida albicans (65%), C. parapsilosis (25%) and C. tropicalis (10%). The median time between admission and onset of candidaemia was greater with C. albicans infection (42.6+/-31 days) than with infection by other yeasts (18+/-12 days). Candidaemia was associated with more extensive burn and longer duration of hospital stay but with similar mortality, compared with controls.
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Extremely low birth weight infants <5 days of age, except those with liver dysfunction, were eligible for fluconazole prophylaxis. NICU infants (all birth weights) with invasive candidiasis between April 2002 and March 2006 were compared with those with invasive candidiasis before fluconazole prophylaxis (2000-2001).
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Variation in the DNA profile and antifungal susceptibility of 271 bloodstream isolates of Candida species was evaluated. The isolates were obtained from 152 nonneutropenic patients hospitalized in 21 different medical centers. In general, each patient was infected with their own distinct DNA type of Candida, and in those cases in which multiple cultures were positive, the same strain was isolated repeatedly over time. Minimum inhibitory concentrations of fluconazole or amphotericin B did not increase over time among the strains isolated repeatedly from individual patients.