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To establish a model of Candida biofilm and to explore its characteristics, ultrastructure, influences by saliva and serum, and sensitivity to antifungal agents.
Fungal exposure is associated with particularly severe asthma. Nevertheless, the effects of anti-fungal treatments on fungus-exacerbated asthma need to be determined.
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To provide evidence-based recommendations for dosing regimens.
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Histoplasmosis is a progressive granulomatous disease caused by the intracellular dimorphic fungus Histoplasma capsulatum. We report a rare case of esophageal histoplasmosis in a renal allograft recipient. A 55-year-old male who received a live, unrelated renal allograft 20 years ago presented with complaints of recurrent fever for ten to 12 months, weight loss over six months, progressive dysphagia more for solids for five to six months and joint pain and swelling involving the bilateral metacarpo-phalangeal and proximal interphalangeal joints. Biopsy from the esophageal ulcers revealed dense inflammation infiltrated with lymphocytes and macrophages with clusters of strongly positive intracellular fungal spores with a clear area or "halo-like" zone suggestive of Histoplasma capsulatum invasion. The patient was treated with intravenous liposomal amphotericin B for ten days and later switched over to oral itraconazole. Repeated endoscopy revealed significant improvement of the lesions.
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To investigate the in vitro antifungal susceptibility pattern of 375 Candida albicans bloodstream isolates recovered during the European Confederation of Medical Mycology survey of candidaemia performed in Lombardia, Italy and to test the ability to form biofilm.
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A 45-year-old woman with breast cancer underwent chemotherapy and radiotherapy as well as autologous peripheral blood stem cell transplantation. She developed a cerebellar aspergillosis abscess that was treated successfully with two surgical resections.
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To evaluate the efficacy and tolerability of high-dose itraconazole for the treatment of MCL.
In 1999, the most strains showed resistance to fluconazole (53.2%), in 2004 to itraconazole (52.9%), and in 2015 to fluconazole (85.8%). Resistance to more than one drug was 35.8% in 1999, 64.7% in 2004, and 92% in 2015. Mean resistance to azole antifungals significantly increased from 98 ± 39.7 strains in 1999 to 118.3 ± 29.6 in 2015 (p < 0.001). In 1999, the most strains showed resistance to fluconazole (50.6%), in 2004 to itraconazole (52.9%), and in 2015 to fluconazole (44.9%). Resistance to more than one drug was 52.9% in 1999, 64.3% in 2004, and 88.1% in 2015. Mean resistance to azole antifungals significantly increased from a mean of 76 ± 9.7 strains in 1999, to 95.3 ± 24.2 in 2004, and to 97.3 ± 16.6 in 2015 (p < 0.001).
The objective of this guideline is to provide recommendations for treating patients with the more common forms of histoplasmosis. PARTICIPANTS AND CONSENSUS PROCESS: A working group of 8 experts in this field was convened to develop this guideline. The working group developed and refined the guideline through a series of conference calls.
Allergic bronchopulmonary aspergillosis is a hypersensitivity disorder that can progress from an acute phase to chronic disease. The main treatment is systemic corticosteroids, but data from uncontrolled studies suggest that itraconazole, an orally administered antifungal agent, may be an effective adjunctive therapy.
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We report eight cases of airway colonization by Geosmithia argillacea in patients with cystic fibrosis. This filamentous fungus, resembling members of the genera Penicillium and Paecilomyces, was identified by molecular analysis. All patients carried a mutation on each CFTR (cystic fibrosis transmembrane conductance regulator) allele, with at least one copy of the F508del mutation. The first isolation of this fungus occurred from F508del-homozygous patients at a younger age than in F508del-heterozygous patients. Before recovery of G. argillacea, all patients were treated with itraconazole; two of them had also received voriconazole for an Aspergillus fumigatus infection. However, antifungal susceptibility patterns showed high MICs of voriconazole for all isolates, and high MICs of amphotericin B and itraconazole for the majority of them, but mostly low minimum effective concentrations (MECs) of caspofungin. The appearance and persistence of G. argillacea in the airways were not associated with exacerbation of the disease. However, the clinical implications of G. argillacea, particularly in immunocompromised patients, remain a concern, particularly given recent observations suggesting that this fungus may also cause disseminated infections.
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Ketoconazole and itraconazole were tested in a multilaboratory study to establish quality control (QC) guidelines for yeast antifungal susceptibility testing. Two isolates that had been previously identified as QC isolates for amphotericin B, fluconazole, and flucytosine (Candida parapsilosis ATCC 22019 and Candida krusei ATCC 6258) were tested in accordance with the National Committee for Clinical Laboratory Standards M27-P guidelines. Each isolate was tested 20 times with the two antifungal agents in the five laboratories by using a lot of RPMI 1640 unique to each laboratory as well as a lot common to all five laboratories, thus generating 200 MICs per drug per organism. Overall, 96 to 99% of the MICs for each drug fell within the desired 3-log2 dilution range (mode +/- 1 log2 dilution). By using these data, 3-log2 dilution QC ranges encompassing 98% of the observed MICs for three of the organism-drug combinations and 94% of the observed MICs for the fourth combination were established. These QC ranges are 0.064 to 0.25 micrograms/ml for both ketoconazole and itraconazole against C. parapsilosis ATCC 22019 and 0.125 to 0.5 micrograms/ml for both ketoconazole and itraconazole against C. krusei ATCC 6258.
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The MICs of amphotericin B, miconazole, ketoconazole, flucytosine, itraconazole and fluconazole for 19 isolates of Fusarium oxysporum, 16 Fusarium solani, seven Fusarium verticilliodes, four Fusarium proliferatum, four Fusarium dimerum, three Fusarium equiseti, and one each of the following species: Fusarium graminearum, Fusarium chlamydosporum, Fusarium semitectum, Fusarium avenaceum and Fusarium subglutinans were determined by a broth microdilution method. Thirty-eight of these isolates were of clinical origin and 20 from environmental sources. In general, Fusarium spp. strains showed resistance to all the antifungals tested. However, the most active agent was amphotericin B. Fluconazole and flucytosine were not active against any of the isolates tested. A correlation study of in-vitro testing with in-vivo outcome of amphotericin B of the cases of disseminated fusarium infections published is reported.
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A 7-year-old boy with Trichophyton tonsurans tinea capitis was cured following the administration of itraconazole oral solution. He had difficulty swallowing tablets or capsules, so the availability of the oral solution was particularly advantageous. The itraconazole was given once daily in a fasting state at a dosage of 3 mg/kg/day as a pulse lasting 1 week. The first two pulses were separated by 2 weeks and the second and third pulse by 3 weeks. The decision whether or not to administer the third pulse was guided by the presence of clinical symptoms and signs of tinea capitis just prior to the scheduled administration. The availability of the oral solution will enable more young children to be considered for treatment of tinea capitis with itraconazole than was possible when only tablets or capsules were available.
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A Medline search was performed for all English language publications from 1966 to June 1999 on the use of terbinafine and itraconazole in the treatment of toenail onychomycosis. Included were randomized studies in which subjects received no less than 3 months (or cycles) and no more than 4 months (or cycles) of either terbinafine or itraconazole. Data were abstracted and statistical analyses (random effects model, fixed effects model, and Peto's method) were applied.
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Invasive pulmonary aspergillosis is an emerging serious infection in patients with COPD. The majority of these patients have advanced COPD and/or on corticosteroid therapy. The clinical and radiological presentation is nonspecific. High index of suspicion is necessary for the timely treatment of these patients.
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Candida parapsilosis (sensu lato), which represents a fungal complex composed of three genetically related species - Candida parapsilosis sensu stricto, Candida orthopsilosis and Candida metapsilosis, has emerged as an important yeast causing fungemia worldwide. The goal of the present work was to assess the prevalence, antifungal susceptibility and production of virulence traits in 53 clinical isolates previously identified as C. parapsilosis (sensu lato) obtained from hospitals located in the Southeast of Brazil. Species forming this fungal complex are physiologically/morphologically indistinguishable; however, polymerase chain reaction followed by restriction fragment length polymorphism of FKS1 gene has solved the identification inaccuracy, revealing that 43 (81.1%) isolates were identified as C. parapsilosis sensu stricto and 10 (18.9%) as C. orthopsilosis. No C. metapsilosis was found. The geographic distribution of these Candida species was uniform among the studied Brazilian States (São Paulo, Rio de Janeiro and Espírito Santo). All C. orthopsilosis and almost all C. parapsilosis sensu stricto (95.3%) isolates were susceptible to amphotericin B, fluconazole, itraconazole, voriconazole and caspofungin. Nevertheless, one C. parapsilosis sensu stricto isolate was resistant to fluconazole and another one was resistant to caspofungin. C. parapsilosis sensu stricto isolates exhibited higher MIC mean values to amphotericin B, fluconazole and caspofungin than those of C. orthopsilosis, while C. orthopsilosis isolates displayed higher MIC mean to itraconazole compared to C. parapsilosis sensu stricto. Identical MIC mean values to voriconazole were measured for these Candida species. All the isolates of both species were able to form biofilm on polystyrene surface. Impressively, biofilm-growing cells of C. parapsilosis sensu stricto and C. orthopsilosis exhibited a considerable resistance to all antifungal agents tested. Pseudohyphae were observed in 67.4% and 80% of C. parapsilosis sensu stricto and C. orthopsilosis isolates, respectively. The secretion of phytase (93% versus 100%), aspartic protease (88.4% versus 90%), esterase (20.9% versus 50%) and hemolytic factors (25.6% versus 40%) was detected in C. parapsilosis sensu stricto and C. orthopsilosis isolates, respectively; however, no phospholipase activity was identified. An interesting fact was observed concerning the caseinolytic activity, for which all the producers (53.5%) belonged to C. parapsilosis sensu stricto. Collectively, our results add new data on the epidemiology, antifungal susceptibility and production of potential virulence attributes in clinical isolates of C. parapsilosis complex.
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Cryptococcosis, caused by Cryptococcus gattii sensu lato, is an emerging disease that was initially found in (sub)tropical regions but recently expanded to temperate regions. Cryptococcus gattii s.l. infections are mostly encountered in healthy individuals, frequently affecting both lungs and the central nervous system (CNS). Usually, C. gattii s.l. is less susceptible to antifungal compounds than its counterpart, C. neoformans s.l. We studied 18 clinical C. gattii s.l. isolates with amplified fragment length polymorphism (AFLP) fingerprinting, mating-typing, multi-locus sequence typing (MLST) and antifungal susceptibility testing. All isolates were C. deuterogattii (genotype AFLP6/VGII), 14 were mating-type α and four were type a. Amphotericin B, itraconazole, voriconazole, posaconazole and isavuconazole showed high activity, with minimum inhibitory concentration (MIC) ranges of 0.063-0.25, 0.031-0.25, 0.031-0.25, 0.031-0.25 and <0.016-0.25 μg mL(-1), respectively. Fluconazole and flucytosine had high geometric mean MICs of 2.07 and 3.7 μg mL(-1), respectively. Most cases occurred in immunocompetent patients (n = 10; 55.6 %) and CNS involvement was the most common clinical presentation (n = 14; 77.8 %). Three patients (16.7 %) showed sequelae, hyperreflexia, dysarthria, diadochokinesia, anosmia and upper limb weakness. In conclusion, all infections were caused by C. deuterogattii (AFLP6/VGII) and the majority of patients were immunocompetent, with the CNS as the most affected site. All antifungal drugs had high in vitro activity against C. deuterogattii isolates, except fluconazole and flucytosine.
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Potentially serious adverse drug interactions can occur between antimicrobial agents used in dental practice and other drugs patients are taking for a variety of medical conditions.
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The aim of this work was to identify the predominant yeast species present at different anatomical sites in healthy dogs and to determine their in vitro antimicrobial susceptibility using a broth microdilution assay. Samples were collected from the preputial, vaginal, oral and perianal mucosae and the isolates cultured were identified according to their morphological characteristics and biochemical profile. Malassezia pachydermatis was the most commonly isolated yeast, followed by Candida parapsilosis, Candida tropicalis, Candida albicans, Saccharomyces cerevisiae and Rhodotorula spp. Minimum inhibitory concentrations of the azole derivatives ketoconazole, itraconazole and fluconazole against Candida spp. were 0.03-16 microg/mL, 0.06 to >16 microg/mL and 0.5-64 microg/mL, respectively and Candida isolates were sensitive to caspofungin and amphotericin B. Although all isolates of M. pachydermatis were sensitive to itraconazole, fluconazole, ketoconazole and amphotericin B, they were found to be resistant to caspofungin. The study has highlighted that Candida spp., M. pachydermatis, S. cerevisiae and Rhodotorula spp. are part of the normal canine surface microbiota and some of these organisms exhibit in vitro resistance to commonly used antimicrobials.
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The system allowed linear and reproducible quantification of the representative target analyte.