A total of 22 proteins were found to be more abundantly represented, and 3 proteins were found to be less abundantly represented, in strain F15 compared with strain 66032. These included up-regulation of the ATP-binding cassette transporter Cdr1p, the ergosterol biosynthesis enzyme Erg11p, proteins involved in glycolysis and glycerol metabolism, and proteins involved in the response to oxidative stress and cadmium exposure.
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According to our analysis, the total cost of allo-HSCT per patient during the 100-day fixed-treatment period was €46,562 in the posaconazole group (n = 33) and €45,080 in the itraconazole group (n = 16). However, the reduction in the incidence of IFI and the improved outcome with posaconazole resulted in a favorable ICER of €11,856 per IFI avoided and €5218 per life-year gained. With the outcomes of the bootstrap procedure, the cost-effectiveness acceptability curve was constructed. Assuming a threshold of €30,000 per life-year gained, the ICER based on life-years gained is acceptable with 75% certainty.
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We retrospectively studied the clinical characteristics and antifungal susceptibility of isolates and risk factors for mortality in 91 cases of candidemia treated from January 1, 2001 to June 30, 2003.
From July 2010 until March 2011, HIV infected adults with a first episode of cryptococcal meningitis were recruited at Queen Elizabeth Central Hospital, Blantyre, Malawi. Patients were treated with oral fluconazole monotherapy 800 mg daily, as per national guidelines. ART was started at 4 weeks. Outcomes and factors associated with treatment failure were assessed 4, 10 and 52 weeks after fluconazole initiation.
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Articles were retrieved form PubMed covering the years 2000-2012. Various search terms were used. Then the articles were clustered in different types like 'review,' 'pharmacokinetics,' 'case reports' and others.
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The results suggest that optimal oral treatment for cryptococcal meningitis is high-dose fluconazole with flucytosine. Efforts are needed to increase availability of flucytosine in Africa. Clinical trials registration. isrctn.org Identifier: ISRCTN02725351.
The antifungal activity of the fractions was evaluated at 500 μg/mL by microdilution method. Checkerboard assay was performed to determine the effect of the combination of the F2 fraction and antifungal at concentrations: MIC/4, MIC/2, MIC, MIC × 2 and MIC × 4.
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Infections caused by Candida spp. and Aspergillus spp. account for 90% of all fungal infections and are the most significant causes of human morbidity and mortality. Candida albicans causes between 50 and 60% of all nosocomial fungal infections. The wet mount test and culture are the screening methods used in leading clinical laboratories for the detection of Candida spp. However, yeasts should be strictly classified mainly based on their physiological and biochemical characteristics, through a series of morphological and biochemical laboratory tests. As a result of the increase in systemic fungal infections and the spread of antifungal medications, it was necessary to establish standardized in vitro sensitivity tests as a guideline for the therapeutic decision-making process. Among antifungal agents available today we find antimycotics such as amphotericin B, 5-fluorocytosine (5-FC), fluconazole, voriconazole, posaconazole, and ravuconazole. Additionally, there is the recently developed group of echinocandines, which includes caspofungin, micafungin and anidulafungine.
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Fungal prosthetic valve endocarditis is an extremely severe form of infective endocarditis, with poor prognosis and high mortality despite treatment. Candida albicans is the most common etiological agent for this rare but increasingly frequent condition. We present a case of fungal prosthetic valve endocarditis due to C. albicans following aortic and pulmonary valve replacement in a 38-year-old woman with a history of surgically corrected tetralogy of Fallot, prior infective endocarditis and acute renal failure with need for catheter-based hemodialysis. Antifungal therapy with liposomal amphotericin B was initiated prior to cardiac surgery, in which the bioprostheses were replaced by homografts, providing greater resistance to recurrent infection. During hospitalization, a mycotic aneurysm was diagnosed following an episode of acute arterial ischemia, requiring two vascular surgical interventions. Despite the complications, the patient's outcome was good and she was discharged on suppressive antifungal therapy with oral fluconazole for at least a year. The reported case illustrates multiple risk factors for fungal endocarditis, as well as complications and predictors of poor prognosis, demonstrating its complexity.
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Morphological effects of itraconazole (ITCZ) on murine macrophages were examined by light microscopy (LM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and compared with the effects of other antifungal agents. Thioglycolate-induced peritoneal macrophages were prepared from C3H/He J mice and cultured for 20 h in the presence of the antifungal azoles econazole, fluconazole, miconazole, ketoconazole, ITCZ, hydroxy-itraconazole (ITCZ-OH), and a polyene antibiotic amphotericin B (AMPH). Among these reagents, only ITCZ and its derivative ITCZ-OH were effective in causing morphological changes of murine macrophage as determined by LM and SEM. Macrophages treated with 2 microg/ml ITCZ or ITCZ-OH were stretched out bidirectionally, their surface was smooth and their 'ruffles' decreased. TEM observation showed that the bundles of the filamentous structure existed along the cell shape in the cytoplasm. These findings suggest that ITCZ and ITCZ-OH affect the morphology of macrophages.
Cryptococcosis is caused by members of the Cryptococcus neoformans/Cryptococcus gattii species complex. Based on molecular identification, these two species have been further differentiated into molecular types. The aim of this work was to characterize clinical cryptococcal isolates recovered from six hospitals in Northeast Mexico from 1995 to 2011. One hundred and sixty-six isolates, which were characterized by biochemical tests and in vitro susceptibility to amphotericin B, fluconazole, and voriconazole, and M13 PCR fingerprinting, were included in this study. Utilizing phenotypic tests, 153 isolates (92.16 %) were identified as C. neoformans and 13 (7.83 %) as C. gattii. All isolates were susceptible to all antifungals tested. Employing M13 PCR fingerprinting, eight molecular types were detected. VNI was the most common genotype (124 cases; 74.6 %), followed by VNII (15 cases; 9 %), VNIII (8 cases; 4.8 %), VNIV (6 cases; 3.6 %), VGI (6 cases; 3.6 %), VGII (3 cases; 1.8 %), and VGIII and VGIV (2 cases, 1.2 % each). We confirm the presence of C. gattii in clinical isolates in Northeast Mexico, and a high clonal diversity in the studied strains of C. neoformans/C. gattii species complex.
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Eleven patients, 81.8% male, were diagnosed during this study. The immunosuppression status was identified in 54.5% of patients, and all of them were under corticosteroid therapy due to a variable set of diseases. All patients presented with circumscribed lesions on their upper limbs. Most lesions showed an infiltrative or tumoral aspect with up to 40 cm diameter. Fluconazole, up to 400 mg/daily, was the main therapeutic regimen and proved to be efficient.
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There is a high interest in Candida species other than Candida albicans because of the rise and the epidemiological shifts in candidiasis. These emerging Candida species are favored by the increase of immunocompromised patients and the use of new medical practices, and m. Most oropharyngeal candidiasis can be foundare observed in those HIV-infected patients infected with human immunodeficiency virus (HIV). Candida dubliniensis is a recently described opportunistic pathogen that is closely related to C. albicans but differs from it with respect to epidemiology, certain virulence characteristics, and the ability to develop fluconazole resistance in vitro. C. dubliniensis has been linked to oral candidiasis in AIDS patients, although it has recently been associated to invasive disease. C. dubliniensis shares diagnostic characteristics with C. albicans, as germ tube- and chlamydospore-production, and it is generally misclassified as C. albicans by standard diagnostic procedures. Several recent studies have attempted to elucidate useful phenotypic and genotypic characteristics for separating both species. A large variety of methods have been developed with the aim of facilitating rapid and, accurate identification of this species. These have included differential chromogenic isolation platesculture media, direct immunological tests, and enhanced manual and automated biochemical and enzymatic panels. Chromogenic isolation media, as CHROMagar Candida, demonstrate better detection rates than traditional media, and allow the presumptive identification of C. dubliniensis by means of colony color (dark-green colonies). API 20 C AUX system is considered a reference method, but ID 32 C strip, the VITEK Yeast Biochemical Card and the VITEK 2 ID-YST system correctly identify most C. dubliniensis isolates, being the latter the most accurate. Spectroscopic methods, such as Fourier transformed-infrared spectroscopy, offer potential advantages. However, many authors consider that standard methods for differentiation of Candida species are time-consuming, often insensitive and can fail to distinguish C. dubliniensis. To overcome these low sensitivity, poor specificity and intolerable delay,drawbacks, molecular tools have been developed to discriminate C. dubliniensis, and particularly those based on the polymerase chain reaction. But, molecular tools prove difficult and too complex for routine use in the clinical laboratory setting and new developments are necessary. Moreover, an increased resistance to antifungal drugs has been described. Although preliminary studies indicate that most strains of C. dubliniensis are susceptible to antifungal agents, fluconazole-resistant strains have been detected. Furthermore, fluconazole-resistant strains are easily derived in vitro, showing an increased expression of multidrug resistance transporters, as MDR1.
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Cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and tumor necrosis factor-soluble receptor (TNF-sR), and adhesion molecules, e.g. vascular adhesion molecule-1 (VCAM-1) and E-selectin, play an important role in the pathogenesis of bacterial sepsis. Experimental data on cytokine expression during candidaemia are controversial. In this study, plasma concentrations of cytokines and adhesion molecules were compared between patients with sepsis due to Candida albicans and bacterial sepsis. Plasma levels of TNF-alpha, TNF-sR, IL-6, VCAM-1 and E-selectin, were determined in 20 patients with sepsis due to C. albicans, in 20 patients with bacterial sepsis, and in 20 controls on days 1, 7 and 14. On day 1, elevated plasma levels of TNF-alpha, TNF-sR and IL-6 were detected in both sepsis groups compared to controls. On day 1, VCAM-1 levels were higher, and E-selectin levels were lower in patients with Candida sepsis than in patients with bacterial sepsis (p < 0.05). At any time, VCAM-1 levels were significantly greater in patients with Candida sepsis than in patients with bacterial sepsis (p < 0.05). Non-survivors, regardless of the etiology of sepsis, had higher blood levels of IL-6, TNF-sR and E-selectin than survivors. The cytokines, TNF-alpha, IL-6 and TNF-sR, and the adhesion molecules, VCAM-1 and E-selectin, are involved in sepsis due to C. albicans as in bacterial sepsis.
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To determine clinical presentation, hospital course, response to treatment, complications developed, in-hospital mortality, any recurrence of cryptococcal meningitis and reasons of recurrence during follow-up.
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The high number of petite mutation in the isolated yeasts should be seriously considered since it may be one of the reasons of antifungal treatment failure.
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Patients in group 1 (n = 21) were given only fluconazole capsules (Zolax 50 mg once a day), those in group 2 (n = 18) were given only hexetidine mouthrinses (Heksoral 0.1%, twice daily), whereas those in group 3 (n = 22) were given both fluconazole capsules and hexetidine mouthrinses for 14 days. The yeast colonies of the saliva samples were counted and calculated as the number of colony forming units per milliliter. The presence of yeasts in the lesion and denture samples were evaluated as present/absent according to their growth on cultures. Candida albicans was identified by means of germ tube analysis.
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In this study, we describe the membrane lipid composition of eight clinical isolates (azole resistant and sensitive strains) of Candida albicans isolated from AIDS/ HIV patients. Interestingly, fluorescence polarization measurements of the clinical isolates displayed enhanced membrane fluidity in fluconazole resistant strains as compared to the sensitive ones. The increase in fluidity was reflected in the change of membrane order, which was considerably decreased (decrease in fluorescence polarization "p" value denotes higher membrane fluidity) in the resistant strains. The ergosterol content in azole susceptible isolates was greater, almost twice as compared to the resistant isolates. However, no significant alteration was observed in phospholipid and fatty acid composition of these isolates. Labeling experiments with fluorescamine dye revealed that the percentage of phosphatidylethanolamine exposed to the membrane's outer leaflet was higher in the resistant strains as compared to the sensitive strains, indicating increased floppase activity of the two major ABC drug efflux pumps, CDR1 and CDR2 possibly due to their overexpression in resistant strains. The results of the present study suggest that changes in the status of membrane lipid phase especially the ergosterol content and increased activity of drug efflux pumps by overexpression ofABC transporters, CDR1 and CDR2 might contribute to fluconazole resistance in C. albicans isolated from AIDS/HIV patients.
We discuss the diagnosis, treatment and prognosis of a Danish male with disseminated coccidioidomycosis. He presented with headaches and slight fever. Examination showed pulmonary, cutaneous and cerebral and cerebellar granulomas, a rare complication. He was treated with intravenously and subsequently orally administered fluconazole. Symptoms and clinical findings regressed during treatment.
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Risk factors for fluconazole-resistant candidaemia in adults with cancer include fluconazole/triazole exposure and GIT surgery. ICU admission, invasive ventilation, renal impairment, age >65 years and prior exposure to corticosteroids and triazoles are risk factors for death. CVAD removal reduced mortality. These findings should be integrated into surveillance and treatment algorithms.
A 26-year-old female patient, suffering from recurrent attacks of ulcerative colitis accompanied by extraintestinal symptoms (erythema nodosum and pyoderma gangrenosum), was evaluated for the effect of antibacterial agents on the intestinal bacteria and their enzymatic activities. The enzymes were assayed both at the onset of disease symptoms and after treatment with each of five drug regimens (fluconazole and cefadroxil, cefuroxime axetil and cestriaxone sodium, ciprofloxacin and cestriaxone sodium, ciprofloxacin alone, and ciprofloxacin, metronidazole, and cephalexin). The activities of azoreductase, nitroreductase, oxidoreductase, glucuronidase, and sulfatase were generally lower following all of the treatments, especially when ciprofloxacin was included. The DNA from each sample was amplified by PCR, using random primers. Profiles of amplified DNA on agarose gels showed different patterns, indicating differences in the microflora before and after the antimicrobial treatments. The clinical response to antibacterial therapy was consistent with the decreased bacterial enzymatic activities and changes in the microbial population. Ciprofloxacin, which was associated with the most dramatic falls in enzymatic activity, also had the best clinical results. We conclude that intestinal bacteria and their enzymes play important roles in ulcerative colitis and that population changes can be monitored using PCR profiles.
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Emergence of Candida species resistant to Amphotericin B and triazole has led to use of echinocandins, mostly caspofungin in the management of invasive candidiasis. There are some published reports of caspofungin resistance in Candida species yet no studies on caspofungin susceptibility pattern of Candida species exist in Indian setup.
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A 60-year-old woman with rheumatoid arthritis, who had been treated with infliximab, presented with uncontrollable wrist arthritis. Fungal arthritis caused by Candida parapsilosis was confirmed by examining her aspirated joint fluid. Her infliximab therapy was interrupted, and antifungal therapy with fluconazole was started. After the fungal infection had been ameliorated, surgical debridement and arthrodesis of the wrist joint were conducted, and her symptoms completely resolved. Although fungal arthritis is rare, it should be considered as a differential diagnosis of exacerbated monoarthritis in patients treated with biological agents.