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The activity of echinocandins, amphotericin B and voriconazole against fluconazole-susceptible and fluconazole-resistant Brazilian Candida glabrata isolates

Mario,Débora Alves Nunes; Denardi,Laura Bedin; Bandeira,Laíssa Arévalo; Antunes,Milene Silva; Santurio,Janio Morais; Severo,Luiz Carlos; Alves,Sydney Hartz
Fonte: Instituto Oswaldo Cruz, Ministério da Saúde Publicador: Instituto Oswaldo Cruz, Ministério da Saúde
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/05/2012 Português
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The extensive use of azole antifungal agents has promoted the resistance of Candida spp to these drugs. Candida glabrata is a problematic yeast because it presents a high degree of primary or secondary resistance to fluconazole. In Brazil, C. glabrata has been less studied than other species. In this paper, we compared the activity of three major classes of antifungal agents (azoles, echinocandins and polyenes) against fluconazole-susceptible (FS) and fluconazole-resistant (FR) C. glabrata strains. Cross-resistance between fluconazole and voriconazole was remarkable. Among the antifungal agents, the echinocandins were the most effective against FS and FR C. glabrata and micafungin showed the lowest minimal inhibitory concentrations.

Comparison of In Vitro Activities of the New Triazole SCH56592 and the Echinocandins MK-0991 (L-743,872) and LY303366 against Opportunistic Filamentous and Dimorphic Fungi and Yeasts

Espinel-Ingroff, Ana
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /10/1998 Português
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The in vitro antifungal activities of SCH56592, MK-0991, and LY303366 against 83 isolates of Acremonium strictum, Aspergillus flavus, Aspergillus fumigatus, Aspergillus terreus, Bipolaris spp., Blastomyces dermatitidis, Cladophialophora bantiana, Fusarium oxysporum, Fusarium solani, Histoplasma capsulatum, Phialophora spp., Pseudallescheria boydii, Rhizopus arrhizus, Scedosporium prolificans, and Sporothrix schenckii were compared. The in vitro activities of these agents against 104 isolates of yeast pathogens of Candida spp., Cryptococcus neoformans, and Trichosporon beigelii were also compared. MICs were determined by following a procedure under evaluation by the National Committee for Clinical Laboratory Standards (NCCLS) for broth microdilution testing of the filamentous fungi (visual MICs) and the NCCLS M27-A broth microdilution method for yeasts (both visual and turbidimetric MICs). The in vitro fungicidal activity of SCH56592 was superior (minimum fungicidal concentrations [MFCs], 0.25 to 4 μg/ml for 7 of 18 species tested) to those of MK-0991 and LY303366 (MFCs, 8 to >16 μg/ml for all species tested) for the molds tested, but the echinocandins had a broader spectrum of fungicidal activity (MFCs at which 90% of strains are inhibited [MFC90s]...

Antifungal Susceptibility of Candida Biofilms: Unique Efficacy of Amphotericin B Lipid Formulations and Echinocandins

Kuhn, D. M.; George, T.; Chandra, J.; Mukherjee, P. K.; Ghannoum, M. A.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /06/2002 Português
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Biofilms, likely the predominant mode of device-related microbial infection, exhibit resistance to antimicrobial agents. Evidence suggests that Candida biofilms have dramatically reduced susceptibility to antifungal drugs. We examined antifungal susceptibilities of Candida albicans and Candida parapsilosis biofilms grown on a bioprosthetic model. In addition to conventional agents, we determined if new antifungal agents (triazoles, amphotericin B lipid formulations, and echinocandins) have activities against Candida biofilms. We also explored effects of preincubation of C. albicans cells with subinhibitory concentrations (sub-MICs) of drugs to see if they could modify subsequent biofilm formation. Finally, we used confocal scanning laser microscopy (CSLM) to image planktonic- and biofilm-exposed blastospores to examine drug effects on cell structure. Candida biofilms were formed on silicone elastomer and quantified by tetrazolium and dry weight (DW) assays. Susceptibility testing of fluconazole, nystatin, chlorhexidine, terbenafine, amphotericin B (AMB), and the triazoles voriconazole (VRC) and ravuconazole revealed resistance in all Candida isolates examined when grown as biofilms, compared to planktonic forms. In contrast, lipid formulations of AMB (liposomal AMB and AMB lipid complex [ABLC]) and echinocandins (caspofungin [Casp] and micafungin) showed activity against Candida biofilms. Preincubation of C. albicans cells with sub-MIC levels of antifungals decreased the ability of cells to subsequently form biofilm (measured by DW; P < 0.0005). CSLM analysis of planktonic and biofilm-associated blastospores showed treatment with VRC...

Cryptococcus neoformans Resistance to Echinocandins: (1,3)β-Glucan Synthase Activity Is Sensitive to Echinocandins

Maligie, Marybeth A.; Selitrennikoff, Claude P.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /07/2005 Português
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(1,3)β-d-Glucan synthase (EC 2.4.1.34. UDP-glucose: 1,3-β-d-glucan 3-β-glucosyltransferase) uses UDP-glucose as substrate and catalyzes the polymerization of glucose ([1,3]-β-linkages) to form the major carbohydrate component of the fungal cell wall. We have optimized in vitro assay conditions for (1,3)β-glucan synthase activity from Cryptococcus neoformans. Cells lysed in 50 mM Tris, pH 7.75, containing 20% glycerol, 2 mM NaF, 1 mM dithiothreitol, 0.1 mM phenylmethylsulfonyl fluoride, 5 mM MgCl2, 0.1% protease and phosphatase inhibitor cocktails, and 60 μM GTPγS produced maximum specific activity in vitro. We tested in vitro C. neoformans (1,3)β-glucan synthase activity against the (1,3)β-glucan synthase inhibitors, caspofungin and cilofungin, and have determined that (1,3)β-glucan synthase activity is very sensitive (apparent Ki of 0.17 ± 0.02 μM and 22 ± 5.7 μM, respectively) to these echinocandins. Taken together with high MICs for C. neoformans (caspofungin MIC, 16 μg/ml; cilofungin MIC, 64 μg/ml), our results indicate that C. neoformans is resistant to caspofungin and cilofungin by a mechanism(s) unrelated to (1,3)β-glucan synthase resistance.

Paradoxical Effect of Echinocandins across Candida Species In Vitro: Evidence for Echinocandin-Specific and Candida Species-Related Differences▿

Chamilos, Georgios; Lewis, Russell E.; Albert, Nathaniel; Kontoyiannis, Dimitrios P.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Português
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Paradoxical growth of some Candida isolates occurs at concentrations above the MIC for echinocandins. In 60 Candida bloodstream isolates from cancer patients (20 C. albicans isolates and 10 isolates each of C. parapsilosis, C. tropicalis, C. krusei, and C. glabrata), paradoxical growth was more frequent with caspofungin than micafungin or anidulafungin, was unrelated to MIC, and was strikingly absent in C. glabrata isolates.

Stimulation of Chitin Synthesis Rescues Candida albicans from Echinocandins

Walker, Louise A.; Munro, Carol A.; de Bruijn, Irene; Lenardon, Megan D.; McKinnon, Alastair; Gow, Neil A. R.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Português
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Echinocandins are a new generation of novel antifungal agent that inhibit cell wall β(1,3)-glucan synthesis and are normally cidal for the human pathogen Candida albicans. Treatment of C. albicans with low levels of echinocandins stimulated chitin synthase (CHS) gene expression, increased Chs activity, elevated chitin content and reduced efficacy of these drugs. Elevation of chitin synthesis was mediated via the PKC, HOG, and Ca2+-calcineurin signalling pathways. Stimulation of Chs2p and Chs8p by activators of these pathways enabled cells to survive otherwise lethal concentrations of echinocandins, even in the absence of Chs3p and the normally essential Chs1p, which synthesize the chitinous septal ring and primary septum of the fungus. Under such conditions, a novel proximally offset septum was synthesized that restored the capacity for cell division, sustained the viability of the cell, and abrogated morphological and growth defects associated with echinocandin treatment and the chs mutations. These findings anticipate potential resistance mechanisms to echinocandins. However, echinocandins and chitin synthase inhibitors synergized strongly, highlighting the potential for combination therapies with greatly enhanced cidal activity.

Clinical Evaluation of the Sensititre YeastOne Colorimetric Antifungal Panel for Antifungal Susceptibility Testing of the Echinocandins Anidulafungin, Caspofungin, and Micafungin▿

Pfaller, M. A.; Chaturvedi, V.; Diekema, D. J.; Ghannoum, M. A.; Holliday, N. M.; Killian, S. B.; Knapp, C. C.; Messer, S. A.; Miskov, A.; Ramani, R.
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
Português
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A commercially prepared, dried colorimetric microdilution panel (Sensititre YeastOne Trek Diagnostic Systems, Cleveland, OH) was compared in three different laboratories with the Clinical and Laboratory Standards Institute (CLSI) reference microdilution method by testing 2 quality control strains, 25 reproducibility strains, and 404 isolates of Candida spp. against anidulafungin, caspofungin, and micafungin. Reference MIC endpoints and YeastOne colorimetric endpoints were read after 24 h of incubation. YeastOne endpoints were determined to be the lowest concentration at which the color in the well changed from red (positive, indicating growth) to blue (negative, indicating no growth). Excellent essential agreement (within 2 dilutions) between the reference and colorimetric MICs was observed. Overall agreement was 100% for all three agents. Categorical agreement ranged from 99.3% (anidulafungin) to 100% (caspofungin, micafungin) and interlaboratory reproducibility was 99%. The YeastOne colorimetric method appears to be comparable to the CLSI reference method for testing the susceptibility of Candida spp. to the echinocandins anidulafungin, caspofungin, and micafungin.

In Vitro Fungicidal Activities of Echinocandins against Candida metapsilosis, C. orthopsilosis, and C. parapsilosis Evaluated by Time-Kill Studies ▿

Cantón, Emilia; Espinel-Ingroff, Ana; Pemán, Javier; del Castillo, Lucas
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
Português
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Anidulafungin, micafungin, and caspofungin in vitro activities against Candida metapsilosis, C. orthopsilosis, and C. parapsilosis were evaluated by MICs and time-kill methods. All echinocandins showed lower MICs (mean MICs, 0.05 to 0.71 mg/liter) and the highest killing rates (−0.06 to −0.05 CFU/ml/h) for C. metapsilosis and C. orthopsilosis rather than for C. parapsilosis (mean MICs, 0.59 to 1.68 mg/liter). Micafungin and anidulafungin killing rates were greater than those determined for caspofungin. None of the echinocandins had fungicidal activity against C. parapsilosis.

Quantitation of Azoles and Echinocandins in Compartments of Peripheral Blood by Liquid Chromatography-Tandem Mass Spectrometry▿ †

Farowski, Fedja; Cornely, Oliver A.; Vehreschild, Jörg J.; Hartmann, Pia; Bauer, Tim; Steinbach, Angela; Rüping, Maria J. G. T.; Müller, Carsten
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
Português
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A rapid turnaround is a prerequisite of therapeutic drug monitoring (TDM). For antifungals, this need is still unmet, since hardly any method has been established to simultaneously quantitate concentrations of different antifungal classes. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed allowing quantitation of anidulafungin (ANF), caspofungin (CSF), isavuconazole (ISC), micafungin (MCF), posaconazole (PSC), and voriconazole (VRC). Quantitation was successful with diluted plasma samples, peripheral blood mononuclear cells (PBMC), polymorphonuclear leukocytes (PMN), and erythrocytes (RBC). A triple quadrupole mass spectrometer in selected reaction monitoring mode was used with positive electrospray ionization. Cells and calibration standards were extracted with acetonitrile containing internal standard. Internal standards were a CSF derivate for echinocandins and itraconazole for triazoles. Chromatographic separation of the supernatant was achieved by a gradient method facilitating a BetaBasic C4 column. Analytes were quantified in a single 8-min run. Calibration curves were linear and fitted using least squares with a weighting factor of the reciprocal concentration. Limits of detection (ng/ml) were ANF...

Susceptibility of Pneumocystis to Echinocandins in Suspension and Biofilm Cultures▿†

Cushion, Melanie T.; Collins, Margaret S.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /10/2011 Português
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The targeted inhibition of cyst but not trophic development by anidulafungin, caspofungin, and micafungin on Pneumocystis murina and Pneumocystis carinii in rodent models of Pneumocystis carinii pneumonia (PCP) was recently reported by us (M. T. Cushion et al., PLoS One 5:e8524, 2010). To better understand the effects of echinocandins on P. carinii, the same three compounds were evaluated in standard suspension and biofilm cultures supplemented with various concentrations of sera using the measurement of ATP as the indicator. In suspension cultures with 1 and 5% serum, anidulafungin was the most active compound but 10 and 20% serum abrogated the efficacy of all three echinocandins. Established biofilm cultures that included both the nonadherent and adherent phases were more resistant to micafungin than caspofungin regardless of serum concentration, while anidulafungin had significant activity at 1 and 5% serum concentrations. Nascent biofilms were mostly affected by anidulafungin in 1 and 5% serum, but none of the compounds showed significant activity in 20% serum. We show for the first time that (i) echinocandins differ in their abilities to deplete the ATP of Pneumocystis in biofilms and in suspension cultures, (ii) this variability mostly reflected the reported efficacies in animal models of infection...

Pharmacodynamics of Echinocandins against Candida glabrata: Requirement for Dosage Escalation To Achieve Maximal Antifungal Activity in Neutropenic Hosts▿

Howard, Susan J.; Livermore, Joanne; Sharp, Andrew; Goodwin, Joanne; Gregson, Lea; Alastruey-Izquierdo, A.; Perlin, D. S.; Warn, Peter A.; Hope, William W.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /10/2011 Português
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Candida glabrata is a leading cause of disseminated candidiasis. The echinocandins are increasingly used as first-line agents for the treatment of patients with this syndrome, although the optimal regimen for the treatment of invasive Candida glabrata infections in neutropenic patients is not known. We studied the pharmacokinetics (PK) and pharmacodynamics (PD) of micafungin, anidulafungin, and caspofungin in a neutropenic murine model of disseminated Candida glabrata infection to gain further insight into optimal therapeutic options for patients with this syndrome. A mathematical model was fitted to the data and used to bridge the experimental results to humans. The intravenous inoculation of Candida glabrata in mice was followed by logarithmic growth throughout the experimental period (101 h). A dose-dependent decline in fungal burden was observed following the administration of 0.1 to 20 mg/kg of body weight every 24 h for all three agents. The exposure-response relationships for each drug partitioned into distinct fungistatic and fungicidal components of activity. Surprisingly, the average human drug exposures following currently licensed regimens were predicted to result in a fungistatic antifungal effect. Higher human dosages of all three echinocandins are required to induce fungicidal effects in neutropenic hosts.

Frequency of Decreased Susceptibility and Resistance to Echinocandins among Fluconazole-Resistant Bloodstream Isolates of Candida glabrata

Pfaller, M. A.; Castanheira, M.; Lockhart, S. R.; Ahlquist, A. M.; Messer, S. A.; Jones, R. N.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /04/2012 Português
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The echinocandin class of antifungal agents is considered to be the first-line treatment of bloodstream infections (BSI) due to Candida glabrata. Recent reports of BSI due to strains of C. glabrata resistant to both fluconazole and the echinocandins are of concern and prompted us to review the experience of two large surveillance programs, the SENTRY Antimicrobial Surveillance Program for the years 2006 through 2010 and the Centers for Disease Control and Prevention population-based surveillance conducted in 2008 to 2010. The in vitro susceptibilities of 1,669 BSI isolates of C. glabrata to fluconazole, voriconazole, anidulafungin, caspofungin, and micafungin were determined by CLSI broth microdilution methods. Fluconazole MICs of ≥64 μg/ml were considered resistant. Strains for which anidulafungin and caspofungin MICs were ≥0.5 μg/ml and for which micafungin MICs were ≥0.25 μg/ml were considered resistant. A total of 162 isolates (9.7%) were resistant to fluconazole, of which 98.8% were nonsusceptible to voriconazole (MIC > 0.5 μg/ml) and 9.3%, 9.3%, and 8.0% were resistant to anidulafungin, caspofungin, and micafungin, respectively. There were 18 fluconazole-resistant isolates that were resistant to one or more of the echinocandins (11.1% of all fluconazole-resistant isolates)...

Species-Specific and Drug-Specific Differences in Susceptibility of Candida Biofilms to Echinocandins: Characterization of Less Common Bloodstream Isolates

Simitsopoulou, Maria; Peshkova, Pavla; Tasina, Efthymia; Katragkou, Aspasia; Kyrpitzi, Daniela; Velegraki, Aristea; Walsh, Thomas J.; Roilides, Emmanuel
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /06/2013 Português
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Candida species other than Candida albicans are increasingly recognized as causes of biofilm-associated infections. This is a comprehensive study that compared the in vitro activities of all three echinocandins against biofilms formed by different common and infrequently identified Candida isolates. We determined the activities of anidulafungin (ANID), caspofungin (CAS), and micafungin (MFG) against planktonic cells and biofilms of bloodstream isolates of C. albicans (15 strains), Candida parapsilosis (6 strains), Candida lusitaniae (16 strains), Candida guilliermondii (5 strains), and Candida krusei (12 strains) by XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] assay. Planktonic and biofilm MICs were defined as ≥50% fungal damage. Planktonic cells of all Candida species were susceptible to the three echinocandins, with MICs of ≤1 mg/liter. By comparison, differences in the MIC profiles of biofilms in response to echinocandins existed among the Candida species. Thus, C. lusitaniae and C. guilliermondii biofilms were highly recalcitrant to all echinocandins, with MICs of ≥32 mg/liter. In contrast, the MICs of all three echinocandins for C. albicans and C. krusei biofilms were relatively low (MICs ≤ 1 mg/liter). While echinocandins exhibited generally high MICs against C. parapsilosis biofilms...

Development of a Luminex-Based Multiplex Assay for Detection of Mutations Conferring Resistance to Echinocandins in Candida glabrata

Pham, Cau D.; Bolden, Carol B.; Kuykendall, Randall J.; Lockhart, Shawn R.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /03/2014 Português
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Echinocandins are the recommended treatment for invasive candidiasis due to Candida glabrata. Resistance to echinocandins is known to be caused by nonsynonymous mutations in the hot spot-1 (HS1) regions of the FKS1 and FKS2 genes, which encode a subunit of the β-1,3-glucan synthase, the target of echinocandins. Here, we describe the development of a microsphere-based assay using Luminex MagPix technology to identify mutations in the FKS1 HS1 and FKS2 HS1 domains, which confer in vitro echinocandin resistance in C. glabrata isolates. The assay is rapid and can be performed with high throughput. The assay was validated using 102 isolates that had FKS1 HS1 and FKS2 HS1 domains previously characterized by DNA sequencing. The assay was 100% concordant with DNA sequencing results. The assay was then used for high-throughput screening of 1,032 C. glabrata surveillance isolates. Sixteen new isolates with mutations, including a mutation that was new to our collection (del659F), were identified. This assay provides a rapid and cost-effective way to screen C. glabrata isolates for echinocandin resistance.

Treatment with echinocandins during continuous renal replacement therapy

González de Molina, Francisco Javier; Martínez-Alberici, Maria de Los Ángeles; Ferrer, Ricard
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Português
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Echinocandins are indicated as first-line treatment for invasive candidiasis in moderate to severe illness. As sepsis is the main cause of acute kidney injury, the combination of echinocandin treatment and continuous renal replacement therapy (CRRT) is common. Optimizing antibiotic dosage in critically ill patients receiving CRRT is challenging. The pharmacokinetics of echinocandins have been studied under various clinical conditions; however, data for CRRT patients are scarce. Classically, drugs like echinocandins with high protein binding and predominantly non-renal elimination are not removed by CRRT, indicating that no dosage adjustment is required. However, recent studies report different proportions of echinocandins lost by filter adsorption. Nevertheless, the clinical significance of these findings remains unclear.

Antifungal Resistance to Fluconazole and Echinocandins Is Not Emerging in Yeast Isolates Causing Fungemia in a Spanish Tertiary Care Center

Marcos-Zambrano, Laura Judith; Escribano, Pilar; Sánchez, Carlos; Muñoz, Patricia; Bouza, Emilio; Guinea, Jesús
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /08/2014 Português
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Accurate knowledge of fungemia epidemiology requires identification of strains to the molecular level. Various studies have shown that the rate of resistance to fluconazole ranges from 2.5% to 9% in Candida spp. isolated from blood samples. However, trends in antifungal resistance have received little attention and have been studied only using CLSI M27-A3 methodology. We assessed the fungemia epidemiology in a large tertiary care institution in Madrid, Spain, by identifying isolates to the molecular level and performing antifungal susceptibility testing according to the updated breakpoints of European Committee for Antimicrobial Susceptibility Testing (EUCAST) definitive document (EDef) 7.2. We studied 613 isolates causing 598 episodes of fungemia in 544 patients admitted to our hospital (January 2007 to December 2013). Strains were identified after amplification and sequencing of the ITS1-5.8S-ITS2 region and further tested for in vitro susceptibility to amphotericin B, fluconazole, posaconazole, voriconazole, micafungin, and anidulafungin. Resistance was defined using EUCAST species-specific breakpoints, and epidemiological cutoff values (ECOFFs) were applied as tentative breakpoints. Most episodes were caused by Candida albicans (46%)...

Efficacy and safety of echinocandins versus triazoles for the prophylaxis and treatment of fungal infections: a meta-analysis of RCTs

Wang, J.-F.; Xue, Y.; Zhu, X.-B.; Fan, H.
Fonte: Springer Berlin Heidelberg Publicador: Springer Berlin Heidelberg
Tipo: Artigo de Revista Científica
Português
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Echinocandins and triazoles were proven to be effective antifungal drugs against invasive fungal infections (IFI), which may cause significant morbidity and mortality in immunocompromised patients. The aim of this study was to compare the efficacy and safety between echinocandins and triazoles for the prophylaxis and treatment of fungal infections. PubMed, Embase, and the Cochrane Library were searched to identify relevant randomized controlled trials (RCTs) up to July 2014. The quality of trials was assessed with the Jadad scoring system. The primary outcomes of interest were treatment success, microbiological success, breakthrough infection, drug-related adverse events (AEs), withdrawals due to AEs, and all-cause mortality. Ten RCTs, involving 2,837 patients, were included, as follows: caspofungin versus fluconazole (n = 1), caspofungin versus itraconazole (n = 1), anidulafungin versus fluconazole (n = 1), micafungin versus fluconazole (n = 4), micafungin versus voriconazole (n = 2), and micafungin versus itraconazole (n = 1). Echinocandins and triazoles showed similar effects in terms of favorable treatment success rate [relative risk (RR) = 1.02, 95 % confidence interval (CI), 0.97–1.08], microbiological success rate (RR = 0.98...

The Effect on Mortality of Fluconazole or Echinocandins Treatment in Candidemia in Internal Medicine Wards

De Rosa, Francesco G.; Corcione, Silvia; Filippini, Claudia; Raviolo, Stefania; Fossati, Lucina; Montrucchio, Chiara; Aldieri, Chiara; Petrolo, Alessia; Cavallo, Rossana; Di Perri, Giovanni
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 04/05/2015 Português
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The incidence of candidemia has increased over the past two decades, with an increased number of cases in Internal Medicine and a prevalence ranging from 24% to 57%. This single-center retrospective study was performed to evaluate the epidemiology and the risk factors associated with mortality of candidemia in patients admitted to Internal Medicine wards (IMWs) of the City of Health and Sciences, Molinette Hospital, Turin, from January 2004 to December 2012. For each patient, demographic, clinical and microbiological data were collected. A case of candidemia was defined as a patient with at least one blood culture positive for Candida spp. Amongst 670 episodes of candidemia, 274 (41%) episodes occurred in IMWs. The mortality was 39% and was associated at multivariate analysis with sepsis, cirrhosis and neurologic diseases, whilst removal of central venous catheter ≤48h was significantly associated with survival. In the 77 patients treated with early antifungal therapy the mortality was 29% and was not significantly different with caspofungin or fluconazole, whilst in patients with definitive therapy the mortality was significantly lower with echinocandins compared to fluconazole (11.7% Vs. 39%; p=0.0289), a finding confirmed by multivariate analysis. The mortality was significantly associated with sepsis...

Candida parapsilosis, C. orthopsilosis y C. metapsilosis: epidemiología de las candidemias, patrones de sensibilidad y mecanismos de resistencia a las equinocandinas

Martí Carrizosa, Mar
Fonte: [Barcelona] : Universitat Autònoma de Barcelona, Publicador: [Barcelona] : Universitat Autònoma de Barcelona,
Tipo: Tesis i dissertacions electròniques; info:eu-repo/semantics/doctoralThesis; info:eu-repo/semantics/publishedVersion
Publicado em //2015 Português
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En el treball que es presenta, es va realitzar un estudi retrospectiu analitzat les candidèmies diagnosticades al llarg de 15 anys en el servei de Microbiologia de l'Hospital de la Santa Creu i Sant Pau de Barcelona. S'avaluà la implicació de C. parapsilosis complex com agent causal de candidèmia, la seva distribució percentual segons les altres especies de Candida i en funció de l'edat del pacient, així com la seva evolució al llarg dels anys i la prevalença de les tres especies del complexa: C. parapsilosis sensu stricto, C. orthopsilosis i C. metapsilosis. Es va estudiar la seva sensibilitat enfront els nou antifúngics d'ús sistèmic actualment aprovats i es van analitzar els possibles mecanismes de resistència intrínseca i adquirida a les equinocandines. C. parapsilosis complex va resultar ser la segona espècie més freqüent causant de fungèmia (20%), davant de C. tropicalis (14,4%) i C. glabrata (11,7%) i només darrera de C. albicans (43,1%). Amb una incidència molt més elevada en els pacients pediàtrics (≤ 1 any: 66.7%; 2-14 anys: 50%). Durant aquest període, la seva incidència augmentà lleugerament (0,33%/any). Els estudis de sensibilitat van mostrar una excel·lent activitat dels 9 antifúngics avaluats enfront a la gran majoria dels aïllats...

Novel, broad-specrum antimycotic agents: the role of echinocandins today

Manfredi,Roberto
Fonte: Sociedad Venezolana de Farmacológia y Farmacológia Clínica y Terapéutica. Escuela de Medicina; José Maria Vargas. Cátedra de Farmacológia, piso 3, esquina san jacinto, San José Caracas Publicador: Sociedad Venezolana de Farmacológia y Farmacológia Clínica y Terapéutica. Escuela de Medicina; José Maria Vargas. Cátedra de Farmacológia, piso 3, esquina san jacinto, San José Caracas
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/09/2010 Português
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The echinocandins show comparable efficacy in the treatment of candidemia and invasive candidiasis. Caspofungin and micafungin appear to be similarly efficacious in salvage therapy in aspergillosis; anidulafungin has excellent in vitro activity against Aspergillus species but as yet there are no sufficient clinical data for anidulafungin in this disease state. Each drug has minor advantages and disadvantages compared to the others of the same classe; however, there are large differences in the approved indications for the different drugs. The formulary selection process should consider the direct and indirect costs of the single agents; the characteristics of the patient population at risk for invasive mycosis, such as frequent use of interacting drugs and the burden of monitoring plasma drug levels of drugs; and the implications of using products for indications which have not been still approved (off-label indications).