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Infections due to Candida spp. are frequent, particularly in immunocompromised and intensive care unit patients. Antifungal susceptibility tests are now required to optimize antifungal treatment given the emergence of acquired antifungal resistance in some Candida species. An antifungal susceptibility automated method, the Vitek 2 system (VK2), was evaluated. VK2 was compared to the CLSI broth microdilution reference method and the Etest procedure. For this purpose, 205 clinical isolates of Candida spp., including 11 different species, were tested for fluconazole, voriconazole, and amphotericin B susceptibility. For azoles, essential agreement ranged from 25% to 100%, depending on the method used and the Candida species tested. Categorical agreements for all of the species averaged 92.2% and ranged from 14.3 to 100%, depending on the 24-h or 48-h MIC reading by the Etest and CLSI methods and on the Candida species. Results obtained for Candida albicans showed excellent categorical and essential agreements with the two comparative methods. For Candida glabrata, the essential agreement was high with the CLSI method but low with the Etest method, and several very major errors in interpretation were observed between VK2 and the Etest method for both azoles. Low MICs of fluconazole were obtained for all of the Candida krusei isolates, but the VK2 expert software corrected all of the results obtained to resistant. Amphotericin B results showed MICs of < or = 1 mg/liter for 201 (VK2), 190 (CLSI), and 202 (Etest) isolates. The AST-YS01 Vitek 2 card system (bioMérieux) is a reliable and practical standardized automated antifungal susceptibility test. Nevertheless, more assays are needed to better evaluate C. glabrata fluconazole sensitivity.
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The biosynthesis of melanin has been linked with virulence in diverse pathogenic fungi. Penicillium marneffei, a dimorphic fungus, is capable of melanization in both mycelial and yeast phases, and the pigment may be produced during infection to protect the fungus from the host immune system. To investigate the impact of yeast morphological transformation on antifungal susceptibility, P. marneffei was cultured on various media including minimal medium, 1 % tryptone, brain heart infusion broth, and malt extract broth by using the standardized susceptibility protocol (the M27-A protocol, RPMI medium) for yeasts. We also investigated whether P. marneffei melanization affected its susceptibility to antifungal drugs by adding L-DOPA into culture broths. There were no differences in the minimum inhibitory concentrations of P. marneffei yeast cells previously grown in various culture broths with or without L-DOPA using the M27A protocol (into which no melanin substrate can be added due to a rapid colour change of the RPMI medium to black) for testing amphotericin B, clotrimazole, fluconazole, itraconazole and ketoconazole. However, both melanized and non-melanized P. marneffei displayed increased resistance to antifungal drugs when L-DOPA was added into a selected assay medium, 0.17 % yeast nitrogen base, 2 % glucose, and 1.5 % agar. Hence, active melanin formation appears to protect P. marneffei by enhancing its resistance to antifungal drugs.
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A multicenter study was performed between April and September 1998 with the participation of 12 medical centers located in 8 different provinces and in the capital city of Argentina. The aim of this study was to determine the species distribution and the antifungal susceptibility profile of isolates causing nosocomial fungal infections. All the fungal isolates obtained were sent to the Mycology Department for reference identification and antifungal susceptibility testing. Eighty-nine isolates were received from different clinical specimens. The distribution of species obtained was C. albicans (50.6%), C. tropicalis (22.5%), C. parapsilosis (20.2%), C. krusei (3.4%), C. glabrata (2.2%) and Debaryomyces hansenii (1.1%). Most of the isolates (85/88) had MICs for amphotericin B < or = 1 microgram/ml, C. krusei showed resistance to fluconazole but was dose dependent susceptible to itraconazole, C. glabrata (2/2) were resistant against both drugs, most of the isolates of C. albicans, C. tropicalis and C. parapsilosis were susceptible to these triazole drugs. These data showed a different distribution of Candida species compared with results obtained in other countries. The low frequency of appearance of C. krusei and C. glabrata in our country suggests a reduced selective pressure by triazoles.
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Prosthetic joint infection was associated with long-term antibiotic treatment and multiples previous surgeries. Treatment with fluconazol and debridement or two stage replacement with a spacer was associated with a high failure rate.
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The performance of Etest in fluconazole and voriconazole testing of 279 isolates of uncommon Candida spp. was assessed in comparison with the National Committee for Clinical Laboratory Standards (NCCLS)-approved standard broth microdilution (BMD) method. The NCCLS method employed RPMI 1640 broth medium, and MICs were read after incubation for 48 h at 35 degrees C. Etest MICs were determined with RPMI agar containing 2% glucose and were read after incubation for 48 h at 35 degrees C. The isolates include Candida krusei, C. lusitaniae, C. guilliermondii, C. kefyr, C. rugosa, C. lipolytica, C. pelliculosa, C. dubliniensis, C. famata, C. zeylanoides, C. inconspicua, and C. norvegensis. Overall agreement between Etest and BMD MICs was 96% for fluconazole and 95% for voriconazole. Where a discrepancy was observed between Etest and the reference method, the Etest tended to give lower values with both fluconazole and voriconazole. The Etest method using RPMI agar appears to be a useful method for determining fluconazole and voriconazole susceptibilities of uncommon species of Candida.
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The top three commonest fungus of Beijing Tong Ren hospital successively are Fusarium sp., Aspergrium sp. and Alternaria sp. Natamycin should be the first choice for fusarium infection and pathogen-unknown infection. All species with the exception of Fusarium sp. are sensitive to natamycin, terbinafine and amphotericin B but not itraconazole. Almost all fungal strains are resistant to fluconazole.
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We investigated the effects of lactoferrin (Lf)-related compounds on growth inhibition of Candida albicans by neutrophils or antifungal agents in vitro. Human neutrophils partially inhibited the growth of C.albicans. The growth inhibition caused by human neutrophils was augmented by the addition of human Lf at concentrations which did not show any inhibitory effect in the absence of neutrophils. Similar observations were obtained also with the following combinations: human neutrophils + bovine Lf, murine neutrophils + bovine Lf, and murine neutrophils + iron saturated bovine Lf, but not in the case of murine neutrophils + human transferrin. The minimum inhibitory concentration (MIC) of azole antifungal agents, clotrimazole, ketoconazole, fluconazole, and itraconazole was reduced by 1/4 to 1/16 in the presence of a sub-MIC level of each of bovine Lf, bovine Lf pepsin hydrolysate, and the antimicrobial peptide "lactoferricin B" (Lfcin B). Other types of antifungal agents, amphotericin B, nystatin, and flucytosine did not show such combined effects with these Lf-related compounds. The anti-Candida activity of bovine Lf or Lfcin B in combination with clotrimazole was shown to be synergistic by checkerboard analysis. Clinically isolated azole-resistant C. albicans strains were more susceptible to bovine Lf or Lfcin B than azole-susceptible strains. Trailing growth of an azole-resistant strain in the presence of fluconazole was reduced by the addition of sub-MIC levels of bovine Lf or Lfcin B. These results suggest that Lf-related compounds even at relatively low concentrations may function as an antifungal effector in combination with neutrophils thereby modulating azole antifungal efficacies in vivo.
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We describe two patients with high-grade glioma undergoing treatment with corticosteroids and chemotherapy who presented with cryptococcal meningitis and sepsis. This report of two cases highlights the importance of examining the efficacy of prophylactic antibiotic and/or antifungal regimens in this patient population due to their increased risk of opportunistic infections.
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Exposure of C. albicans to subinhibitory concentrations of fluconazole in RPMI 1640 in the absence of serum led to up-regulation of the virulence-associated genes SAP4, SAP5 and SAP6 in hyphae and long pseudohyphae. Measurements with green fluorescent protein (GFP)-tagged promoters showed that the fluorescence of SAP4 and SAP6 under these conditions was strongest in the apical tip compartments of these filamentous cells and declined in compartments more proximal to the parent yeast cell. By contrast, SAP5-GFP fluorescence was expressed at similar levels in all cell compartments. Exposure to fluconazole led to significant increases in GFP-SAP4 and -SAP6 fluorescence in the filaments; itraconazole exposure also significantly increased GFP-SAP4 fluorescence, whereas flucytosine had no effect on any of the constructs. In experimentally infected animals, fluorescence of the GFP-SAP promoter fungal cells in kidney tissues was greater than that was seen in vitro for all four SAP constructs: treatment of animals with fluconazole did not significantly increase SAP promoter expression as measured by GFP fluorescence.
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A total of 245 consecutive patients with Candida bloodstream infections who received antifungal therapy.
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A total of 2900 urine samples were analysed in a tertiary care hospital. Candida species isolated from urine samples were subjected to speciation using CHROM agar and standard yeast identification protocol. Antifungal susceptibility testing for fluconazole, voriconazole, flucytosine, amphotericin B was carried out using VITEK-2 compact system of Biomerieux.
Cytostatic chemotherapy of hematological malignancies is often complicated by neutropenia, which increases the risk of infections, especially if the neutrophil count is below 500/microl. Frequently, fever is the first, and in most patients the only, sign of an infection. Unexplained fever is defined as follows: temperature of >/=38.3 degrees C or >/=38.0 degrees C for at least 1 h, or measured twice within 12 h, if the neutrophil count is <500/microl or <1000/microl with predicted decline to 500/microl. Different risk categories can be identified according to the duration of neutropenia: low risk =5 days, intermediate risk 6-9 days, high risk >/=10 days. An empirical mono- or duotherapy with antipseudomonal and antistreptococcal agents should be initiated immediately. In the low risk patient group, oral therapy with cipro-, levo-, or ofloxacin combined with amoxicillin/clavulanic acid is permissible. For standard and high risk patients, monotherapy can be carried out with either ceftazidime, cefepime, piperacillin with tazobactam or a carbapenem. In duotherapy, a single dose of an aminoglycoside is combined with acylaminopenicillin or a cephalosporin of the third or fourth generation. The addition of glycopeptides in empirical therapy should only be considered in the presence of severe mucositis, or if a catheter-associated infection is suspected. If fever persists after 72-96 h of first-line therapy with antibiotics, the regimen should be modified (with the exception of e.g. coagulase-negative staphylococci infections, because these infections take longer to respond). Intermediate risk patients should additionally receive an aminoglycoside after monotherapy (penicillin or a cephalosporin). If a carbapenem was administered for monotherapy, this can be followed by a quinolone and/or a glycopeptide. In the high risk group, the same modifications should be made as in the intermediate risk group but with additional systemic antifungal treatment. In the presence of unexplained fever, fluconazole can be administered at first, but if this fails, amphotericin B (conventional or liposomal), itraconazole, voriconazole or caspofungin should be started. After defervescence to <38 degrees C, treatment should be continued for 7 days if the neutrophil count is <1000/microl, and for 2 days if the neutrophil count is >1000/microl.
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Mice treated orally with voriconazole at >or=10 mg/kg and fluconazole at >or=20 mg/kg showed significantly reduced fungal counts over controls (P = 0.0002-0.007). Significant differences were found between the groups that received voriconazole at 20 mg/kg once or twice daily and those that received fluconazole at 20 mg/kg once or twice daily, orally (P = 0.010 and 0.001, respectively). Mice treated with voriconazole or fluconazole administered intravaginally at >or=0.5 mg/kg exhibited a reduced fungal burden when compared with the control group (P = 0.0002-0.007). There was no statistically significant difference in fungal burden between topical treatment with doses of 0.5, 1 and 5 mg/kg once daily of voriconazole or fluconazole. Sterilization of vaginas was not observed with voriconazole and fluconazole without taking into consideration the therapeutic modality.
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This is the case of a 66 year old male who underwent surgery due to peritonitis secondary to intestinal suture dehiscence. The patient was admitted to ICU with septic shock symptoms and multiple organ dysfunction syndrome (MODS), and CRRT was started. Anidulafungin was prescribed at the usual dosage due to the IC risk factors present, and the observation of yeasts in the peritoneal fluid. Anidulafungin was selected due to the hepatic failure suffered by the patient. An isolate of Candida albicans susceptible to fluconazole was cultured from peritoneal fluid and rectal exudates. However, anidulafungin was maintained due to the MODS and observing the clearance of fluconazole during CRRT. The patient's condition improved favourably, being moved to the surgical ward 20 days after the surgery.
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To compare the therapeutic effects of three different anti-fungal drugs (i.e., terbinafine, fluconazole and intraconazole) in the treatment of experimental vaginitis caused by Candida albicans (C. albicans) in mice, the fungal vaginitis model was established in female ICR mice by intravaginal inoculation of suspension of C. albicans after the animal had been pretreated with estradiol. Mice were divided at random into different groups and then respectively treated with terbinafine, fluconazole and intraconazole given by gastrogavage. The burden of the fungus in the vaginal lavage fluids in the mice of the different groups was measured dynamically at different time points after the beginning of the drug treatment. The fungal burdens in the vaginal lavage fluids taken at different time points from the mice treated with terbinafine were significantly higher than those taken at corresponding time points from mice treated with fluconazole or itraconazole (P<0.01). The fungal burdens in the vaginal lavage fluids taken from mice 1 week after the beginning of the treatment with terbinafine remained at a relatively high level. A dramatic drop in the fungal burden was noted in the vaginal lavage fluids taken on the 2nd day of the treatment from mice treated with itraconazole or fluconazole group and the fungal burden on the 3rd day of the treatment in these mice were at a very low level, suggesting that fluconazole or itraconazole were highly effective for the treatment. However, the difference in the therapeutic effect between the two drugs was not significant (P>0.05). Itraconazole or fluconazole, but not terbinafine, is very effective for the treatment of fungal vaginitis caused by C. albicans in mice.
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Combinations of flucytosine with conventional and new antifungals were evaluated in vitro against 30 clinical isolates of Cryptococcus neoformans. Synergy determined by checkerboard analysis was observed with combinations of fluconazole, itraconazole, voriconazole, amphotericin B, and caspofungin with flucytosine against 77, 60, 80, 77, and 67% of the isolates, respectively. Antagonism was never observed. Killing curves showed indifferent interactions between triazoles and flucytosine and synergy between amphotericin B and flucytosine.
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The decision model indicated that voriconazole prophylaxis was cost-effective for patients undergoing allogeneic HCT for AML.
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Midazolam is used for sedation of intensive care unit (ICU) patients and it is extensively metabolised by CYP3A4 enzymes. The antimycotic fluconazole is often used in these patients as well and has been shown to inhibit CYP3A4-mediated drug metabolism.
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Vulvovaginal candidiasis (VVC) is a common gynecological finding among the women worldwide. Candida species are often less susceptible to antifungal agents. Owing to this fact, in this study, we aimed at assessing the prevalence rate and antimicrobial susceptibility pattern of various azoles against Candida species causing VVC in symptomatic women.
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A retrospective study was conducted in 809 patients starting warfarin therapy after HVR. The relationships between 12 polymorphisms plus 47 drugs and primary outcomes of the time to the first international normalized ratio (INR) ≥ 1.8 and the time to the first INR > 3.5 and the secondary outcomes of the proportion of time INR < 1.8, the proportion of time INR > 3.5, and the daily warfarin dose in the first 28 days after the initiation of warfarin treatment were analyzed.
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The authors retrospectively reviewed the microbiology and corresponding clinical records of patients diagnosed as having culture-proven EFE at the Bascom Palmer Eye Institute during a 10-year period.
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It was of interest to investigate the factors affecting kinetics of transformation of fluconazole polymorph II (the metastable form) to fluconazole polymorph I (the stable form) using diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS).
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This study found that the most common otomycotic fungal pathogen was A fumigatus, and that voriconazole had more potent in vitro activity than itraconazole against all Aspergillus species as well as against C albicans.