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Onychomycosis is a public health concern because of its high worldwide incidence and prevalence, and its potential for spread of fungal elements to others, as well as complications such as cellulitis, bacterial infection, pain, and extensive dermatophytic infections. The incidence of onychomycosis has been increasing, particularly in individuals over 60 years of age, patients with HIV infection, and patients with diabetes mellitus. Onychomycosis may impact upon physical, functional, psychosocial, and emotional aspects of life. Difficulty walking, wearing shoes, and embarrassment are common complaints. Quantification of such quality-of-life changes are significant to clinical practice in that many factors can affect overall patient health. In light of the potential clinical implications on physical and mental health, onychomycosis should be considered a medical condition that deserves rigorous clinical management. Onychomycosis can be treated effectively and with comparative safety with the new generation of oral antifungal agents (itraconazole, fluconazole and terbinafine). Significantly improved pharmacokinetic and pharmacodynamic profiles permit markedly reduced duration of administration, individual drug exposure, and ultimately enhanced patient compliance and satisfaction with therapy. In addition, a number of pharmacoeconomic studies have documented the cost effectiveness of these newer agents compared with both traditional pharmacologic treatment and topical therapies. The currency figures quoted are 1997 values. With regard to continuous oral antifungal regimens, terbinafine therapy has been found to be most cost effective in the treatment of toenail onychomycosis, with a drug acquisition cost of $US522.50. However, improved safety, tolerability, efficacy and cost effectiveness have been documented with itraconazole intermittent, pulse regimens. With itraconazole pulse therapy, the drug acquisition cost decreases to $US488.90. Additionally, the total cost of medical management is less for itraconazole therapy compared with that of terbinafine ($US261.00 vs $US306.00). Because sensitivity analyses for itraconazole and terbinafine have been found to be somewhat comparable in terms of mycological cure, clinical response, and relapse rates, other variables such as safety and efficacy profiles, and patient attitudes and expectations toward therapy need to be considered when formulating an onychomycosis pharmacologic treatment plan. The drug aquisition cost of fluconazole given as a 300 mg dose once weekly for 6 months is $US562.76 and given as a 150 mg dose once weekly (for 6 months) $US281.38.
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Whether echinocandins could be used to treat candidemia of a urinary tract source (CUTS) is unknown. We aimed to provide current epidemiological information of CUTS and to compare echinocandin to fluconazole treatment on CUTS outcomes.
Posaconazole is a novel lipophilic antifungal triazole that inhibits cytochrome P450-dependent 14-alpha demethylase in the biosynthetic pathway of ergosterol. Inhibition of this enzyme leads to an accumulation of toxic 14-alpha methylsterols and a depletion of ergosterol, resulting in a perturbation of the function of the fungal cell membrane and blockage of cell growth and division. In vitro, posaconazole has potent and broad-spectrum activity against opportunistic, endemic and dermatophytic fungi. This activity extends to organisms that are often refractory to existing triazoles, amphotericin B or echinocandins, such as Candida glabrata, Candida krusei, Aspergillus terreus, Fusarium spp. and the Zygomycetes. A large variety of animal models of invasive fungal infections have provided consistent evidence of efficacy against these organisms in vivo, both in normal and immunocompromised animals. Posaconazole is available as an oral suspension and optimal exposure is achieved when the drug is administered in two to four divided doses along with food or a nutritional supplement. The compound has a large volume of distribution, in the order of 5 l/kg, and a half-life of approximately 20 h. Posaconazole is not metabolized to a significant extent through the cytochrome P450 enzyme system and is primarily excreted in an unchanged form in the feces. Although it is inhibitory, cytochrome P3A4 has no effect on 1A2, 2C8, 2C9, 2D6 and 2E1 isoenzymes, and therefore, a limited spectrum of drug-drug interactions can be expected. Pharmacokinetic studies in special populations revealed no necessity for dosage adjustment based on differences in age, gender, race, renal or hepatic function. Posaconazole has demonstrated strong antifungal efficacy in Phase II and III clinical trials in immunocompromised patients with oropharyngeal and esophageal candidiasis. Posaconazole also showed promising efficacy as salvage therapy in a large Phase II study including 330 patients with invasive fungal infections intolerant to or refractory to standard therapies. Posaconazole appears to be well tolerated in a manner comparable with that of fluconazole and it is currently under regulatory review in the USA and Europe for the treatment of refractory invasive fungal infections. This drug profile reviews the preclinical and clinical pharmacology of posaconazole and its potential role for prevention and treatment of invasive fungal infections.
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The minimum inhibitory concentrations (MICs) of ginger extract for evaluated strains were 40, 40, 20, 20, 20, 20, 10, and 5 mg/mL for Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Bacillus cereus, Acinetobacter baumannii, C. albicans, and C. krusei, respectively. Ginger extract successfully inhibited biofilm formation by A. baumannii, B. cereus, C. krusei, and C. albicans. MTT assay revealed no significant reduction in cell viability after 24 hours. The minimum inhibitory biofilm concentrations (MIBCs) of ginger extract for fungi strains (C. krusei and C. albicans) were greater than those of fluconazole and nystatin (P = 0.000).
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Vulvovaginal candidiasis (VVC) was a common infection associated with lifelong harassment of woman's social and sexual life. The purpose of this study was to describe the species distribution and in vitroCandidaCandida spp.) isolated from patients with VVC over 8 years.
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The liposome formulation decreased the retinal toxicity of fluconazole up to the studied concentration of 200 microg/0.1 ml.
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Experimental data have implicated intravenous lipids as being immunosuppressive, yet evidence that lipids are associated with an increase in clinically documented infections is sparse. A prospective trial conducted in patients with hematologic malignancies who were undergoing bone marrow transplantation compared the incidence of bacteremia and fungemia during the first month after the transplant. Patients (n = 512) were randomly assigned to receive 6-8% (low dose) or 25-30% (standard dose) of total daily energy as a 20% lipid emulsion. An adaptive randomization scheme stratified for treatments that might influence infection outcome (hematopoietic growth factors, fluconazole, graft-versus-host disease prophylaxis with steroids, pentoxifylline, intravenous immunoglobulin, and total body irradiation). The transplant type (autologous, related family donor, or unrelated donor) did not differ in distribution between treatment groups. Of the evaluable patients (n = 482), 55 patients in the standard-dose lipid group developed bacteremia or fungemia compared with 54 in the low-dose lipid group. The log-rank test comparing the time to first infection found no association between the incidence of bacteremia or fungemia and intravenous lipid (P = 0.95). Similar results were found when analyzed as intent-to-treat (P = 0.98), when bacterial or fungal infections at all sites were included (P = 0.94), and when the observation period was extended to 60 d (P = 0.58 for blood infections, P = 0.77 for infections at all sites). These data indicate that moderate amounts of intravenous lipid rich in linoleic acid are not associated with an increased incidence of bacterial or fungal infections in patients undergoing bone marrow transplantation and receiving total parenteral nutrition.
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We encountered a 49-year-old HIV-infected man with chronic renal insufficiency who developed rhabdomyolysis after treatment with simvastatin. He recovered after initiating hemodialysis and discontinuing oral medications. Rhabdomyolysis most likely resulted from an excessive blood concentration of simvastatin caused by concomitant use of fluconazole in the presence of renal insufficiency.
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Invasive fungal infections (IFIs) are a major cause of mortality among allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients. Thanks to the widespread use of secondary antifungal prophylaxis (SAP), a history of IFI is not an absolute contraindication to allo-HSCT. However, IFI recurrence remains a risk factor for transplant-related mortality.