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1.
Transpl Infect Dis ; 16(2): 213-24, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24589027

RESUMO

BACKGROUND: Invasive fungal infections are a major cause of morbidity and mortality among solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients, but few data have been reported on the epidemiology of endemic fungal infections in these populations. METHODS: Fifteen institutions belonging to the Transplant-Associated Infection Surveillance Network prospectively enrolled SOT and HCT recipients with histoplasmosis, blastomycosis, or coccidioidomycosis occurring between March 2001 and March 2006. RESULTS: A total of 70 patients (64 SOT recipients and 6 HCT recipients) had infection with an endemic mycosis, including 52 with histoplasmosis, 9 with blastomycosis, and 9 with coccidioidomycosis. The 12-month cumulative incidence rate among SOT recipients for histoplasmosis was 0.102%. Occurrence of infection was bimodal; 28 (40%) infections occurred in the first 6 months post transplantation, and 24 (34%) occurred between 2 and 11 years post transplantation. Three patients were documented to have acquired infection from the donor organ. Seven SOT recipients with histoplasmosis and 3 with coccidioidomycosis died (16%); no HCT recipient died. CONCLUSIONS: This 5-year multicenter prospective surveillance study found that endemic mycoses occur uncommonly in SOT and HCT recipients, and that the period at risk extends for years after transplantation.


Assuntos
Blastomicose/epidemiologia , Coccidioidomicose/epidemiologia , Doenças Endêmicas , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Histoplasmose/epidemiologia , Transplante de Órgãos/efeitos adversos , Adolescente , Adulto , Idoso , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Blastomicose/tratamento farmacológico , Criança , Coccidioidomicose/tratamento farmacológico , Coinfecção/tratamento farmacológico , Coinfecção/epidemiologia , Comorbidade , Feminino , Histoplasmose/tratamento farmacológico , Humanos , Incidência , Itraconazol/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , Fatores de Tempo , Estados Unidos/epidemiologia , Adulto Jovem
2.
Clin Microbiol Infect ; 18(2): E20-3, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22128831

RESUMO

We compared the rate and extent of anidulafungin's and fluconazole's activity in neutropenic and non-neutropenic mice with Candida albicans invasive candidiasis. In immunocompetent mice, anidulafungin significantly improved survival vs. controls and fluconazole, and significant reductions in (1→3)-ß-D-glucan and fungal burden were observed. In neutropenic animals, the highest doses of anidulafungin (5 mg/kg) and fluconazole (10 mg/kg) also improved survival and reduced fungal burden. However, there were no differences in survival between these antifungals as anidulafungin's activity was attenuated in this model. These results demonstrate that the extent of anidulafungin in vivo efficacy may be dependent on host immune status.


Assuntos
Antifúngicos/administração & dosagem , Candida albicans/efeitos dos fármacos , Candidíase Invasiva/tratamento farmacológico , Equinocandinas/administração & dosagem , Fluconazol/administração & dosagem , Anidulafungina , Animais , Sangue/microbiologia , Análise Química do Sangue , Candida albicans/isolamento & purificação , Candidíase Invasiva/microbiologia , Contagem de Colônia Microbiana , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos ICR , Neutropenia/complicações , Proteoglicanas , Análise de Sobrevida , Resultado do Tratamento , beta-Glucanas/sangue
3.
Eur J Clin Microbiol Infect Dis ; 29(11): 1387-94, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20703506

RESUMO

In a non-comparative study, caspofungin was effective salvage therapy for approximately half of the patients refractory to or intolerant of standard antifungal agents for invasive aspergillosis. To establish a frame of reference for these results, we compared the response to caspofungin with responses to other antifungal agents in a historical cohort of similar patients. The efficacy could be evaluated in 83 patients who received caspofungin 50 mg daily after a 70-mg loading dose. The historical control group, identified through a retrospective review of medical records, included 214 evaluable patients possibly refractory to or intolerant of ≥1 week of standard antifungal therapy. All patients had documented invasive aspergillosis. Favorable response was defined as a complete or partial response to therapy. Underlying diseases, baseline neutropenia, corticosteroid use, and sites of infection were similar in both studies. Most patients had received amphotericin B formulations and/or itraconazole, and were refractory to standard therapy. Favorable response rates were 45% with caspofungin and 16% with standard therapy. The unadjusted odds ratio for a favorable response (caspofungin/standard therapy) was 4.1 (95% confidence interval: 2.2, 7.5). After adjusting for potential imbalances in the frequency of disseminated infection, neutropenia, steroid use, and bone marrow transplantation between groups, the odds ratio remained at 4.1 (2.1, 7.9). Although only tentative conclusions about relative efficacy can be drawn from retrospective comparisons, caspofungin appeared to be at least as efficacious as an amphotericin B formulation and/or itraconazole for the treatment of invasive aspergillosis in patients refractory to or intolerant of their initial antifungal therapy.


Assuntos
Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Equinocandinas/uso terapêutico , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Terapia de Salvação , Adolescente , Adulto , Idoso , Anfotericina B/administração & dosagem , Anfotericina B/uso terapêutico , Antifúngicos/administração & dosagem , Aspergilose/microbiologia , Aspergillus/efeitos dos fármacos , Caspofungina , Farmacorresistência Fúngica , Equinocandinas/administração & dosagem , Feminino , Humanos , Aspergilose Pulmonar Invasiva/microbiologia , Itraconazol/administração & dosagem , Itraconazol/uso terapêutico , Lipopeptídeos , Masculino , Pessoa de Meia-Idade , Neutropenia , Prognóstico , Falha de Tratamento , Resultado do Tratamento , Adulto Jovem
4.
J Clin Microbiol ; 47(5): 1325-32, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19261786

RESUMO

Enumerating Aspergillus fumigatus CFU can be challenging since CFU determination by plate count can be difficult. CFU determination by quantitative real-time PCR (qPCR), however, is becoming increasingly common and usually relies on detecting one of the subunits of the multicopy rRNA genes. This study was undertaken to determine if ribosomal DNA (rDNA) copy number was constant or variable among different A. fumigatus isolates. FKS1 was used as a single-copy control gene and was validated against single-copy (pyrG and ARG4) and multicopy (arsC) controls. The copy numbers of the 18S rDNA subunit were then determined for a variety of isolates and were found to vary with the strain, from 38 to 91 copies per genome. Investigation of the stability of the 18S rDNA copy number after exposure to a number of different environmental and growth conditions revealed that the copy number was stable, varying less than one copy across all conditions, including in isolates recovered from an animal model. These results suggest that while the ribosomal genes are excellent targets for enumeration by qPCR, the copy number should be determined prior to using them as targets for quantitative analysis.


Assuntos
Aspergillus fumigatus/genética , DNA Ribossômico/genética , Dosagem de Genes , Genes de RNAr , RNA Ribossômico 18S/genética , Animais
5.
J Clin Pathol ; 62(6): 539-41, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19190008

RESUMO

BACKGROUND: The diagnosis of invasive aspergillosis (IA) remains challenging and frequently is not made until after death. Histopathological examination remains central to confirmation of diagnosis but often requires invasive procedures to obtain tissue for the examination. Detection of aspergillus DNA by quantitative PCR (qPCR) offers the potential for earlier diagnosis due to higher sensitivity, but PCR in clinical use is poorly reproducible, with different centres reporting variable results and often using different extraction and analytical methods. AIMS: To optimise the performance of aspergillus PCR as a diagnostic modality. METHODS: A rat inhalation model of invasive aspergillosis was used to optimise the methodology of diagnostic aspergillus PCR. Infected animals were terminally bled at 4 days post-infection; samples of EDTA blood, serum and the residual clot were pooled for subsequent analysis. DNA was extracted from each fraction using a variety of methods and an optimised qPCR reaction using an Aspergillus fumigatus primer set performed. RESULTS: Significantly more aspergillus DNA was detected from the clot than EDTA and serum samples. Enzymatic and mechanical pretreatment reduced the yield of fungal DNA. There was some evidence that the average Ct values were greater for the EZ1 BioRobot than the MagNA Pure automated extractor, but this did not reach statistical significance at the 5% level (p = 0.078). CONCLUSIONS: Automated extraction from the clot present in a blood sample will increase DNA yield and improve the diagnostic sensitivity of the test.


Assuntos
Aspergilose/diagnóstico , Aspergillus fumigatus/genética , DNA Fúngico/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Trombose/microbiologia , Animais , Anticoagulantes , Sequência de Bases , Primers do DNA/genética , Ácido Edético , Modelos Animais , Dados de Sequência Molecular , Técnicas de Tipagem Micológica , Ratos
6.
Transpl Infect Dis ; 11(1): 89-93, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18983417

RESUMO

We describe herein 98 hematopoietic stem cell transplant (HSCT) recipients with invasive aspergillosis (IA) (refractory in 83) who received micafungin either alone (8 patients) or in combination with other licensed antifungal therapies (OLAT) (90 patients). Of the 8 monotherapy patients, 4 were failing OLAT, received de novo micafungin, or were intolerant to prior OLAT (2 patients each). Of the 90 patients treated with combination, 7 had de novo IA and 83 had refractory infection. Most patients (81) had pulmonary IA, 42 (43%) had graft-versus-host disease (GVHD), and 26 (27%) were neutropenic (absolute neutrophil count <500 cells/mm(3)) at onset of treatment. Successful response was seen in 25/98 (26%); an additional 12 patients achieved stable disease. Response was seen in 2/9 (22%) in de novo treatment, 21/87 (24%) in refractory patients, and 2/2 (100%) in toxicity failure patients. Additionally, response was seen in 22 of the 90 (24%) patients treated with combination therapy, and in 3 of 8 (38%) patients who were treated with micafungin alone. No significant differences in responses were found based on type of HSCT, GVHD status, site of IA, or Aspergillus species, and no significant toxicity was seen. Micafungin was well tolerated, even at high doses, and is a reasonable option for treatment of IA in this high-risk patient population.


Assuntos
Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Equinocandinas/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Lipopeptídeos/uso terapêutico , Adulto , Antifúngicos/administração & dosagem , Aspergilose/microbiologia , Aspergillus/efeitos dos fármacos , Criança , Quimioterapia Combinada , Equinocandinas/administração & dosagem , Humanos , Aspergilose Pulmonar Invasiva/microbiologia , Lipopeptídeos/administração & dosagem , Micafungina , Resultado do Tratamento
7.
Clin Microbiol Infect ; 14(6): 595-600, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18397335

RESUMO

Extended interval dosing of the echinocandins has been suggested as a potential strategy to overcome the need for daily intravenous administration. This study evaluated the therapeutic and prophylactic efficacy of single doses of aminocandin, a new echinocandin in preclinical development, in a murine model of invasive candidiasis. For therapy, groups of mice were infected with Candida albicans, followed by a single dose of aminocandin (1-15 mg/kg) or placebo (mannitol 5% w/v) administered 1 day after inoculation. As prophylaxis, mice were given a single dose (5 or 30 mg/kg) of aminocandin, caspofungin, or placebo at increasing intervals between dose and inoculation. In both treatment and prophylaxis studies, survival was assessed at 21 days post-inoculation. The reduction in fungal burden was assessed in kidney tissue on day 8 post-inoculation. For treatment, single doses of aminocandin of >/=2.5 mg/kg prolonged survival significantly. In addition, the two doses evaluated for reductions in fungal burden (5 and 15 mg/kg) revealed fungicidal activity. As prophylaxis, both aminocandin and caspofungin 5 and 30 mg/kg prolonged survival when given 7 days before inoculation. Aminocandin and caspofungin 30 mg/kg were both able to prolong survival when the interval between dose and inoculation was increased to 10 days. When this interval was extended to 14 days, only aminocandin 30 mg/kg prolonged survival and reduced fungal burden. These results demonstrate that single doses of aminocandin are effective as treatment and prophylaxis, and suggest that extended interval dosing may be a useful strategy for treating invasive candidiasis.


Assuntos
Antifúngicos/uso terapêutico , Candidíase/tratamento farmacológico , Candidíase/prevenção & controle , Lipoproteínas/uso terapêutico , Animais , Antifúngicos/administração & dosagem , Candida albicans/efeitos dos fármacos , Caspofungina , Contagem de Colônia Microbiana , Intervalo Livre de Doença , Equinocandinas/administração & dosagem , Equinocandinas/uso terapêutico , Rim/microbiologia , Lipopeptídeos , Lipoproteínas/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos ICR
9.
Med Mycol ; 43 Suppl 1: S115-9, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-16110802

RESUMO

The diagnosis of invasive aspergillosis remains very difficult, coupled with limited treatment options. Animal models have been utilized to evaluate both the diagnosis and treatment of infection and to assess the pathogenicity and virulence of the organism. However, animal models have not been standardized and have been used in only a limited fashion for genomic evaluation in this disease. Extensive efforts are underway to expand significantly the Aspergillus genomic information. Thus, the standardization of animal models of invasive aspergillosis is critical to create a unified platform to enhance evaluation of newer genomic information and allow assessment of pathogenicity and virulence factors. Proposed models, supported by a recently awarded National Institutes of Health/National Institute of Allergy and Infectious Diseases contract, will be developed in close interaction with the extended Aspergillus community (including academia and industry) to answer key questions in this disease. The goal of this work is to provide the framework to evaluate genomic targets in animal models in order to improve the diagnosis and treatment of invasive aspergillosis that will ultimately result in improved outcomes of patients with this frequently fatal infection.


Assuntos
Aspergilose/fisiopatologia , Aspergillus/patogenicidade , Modelos Animais de Doenças , Animais , Aspergilose/microbiologia , Humanos , Pneumopatias Fúngicas/microbiologia , Pneumopatias Fúngicas/fisiopatologia , Camundongos , Coelhos , Virulência
10.
Antimicrob Agents Chemother ; 49(8): 3544-5, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16048980

RESUMO

Combinations of caspofungin and posaconazole were evaluated by fractional inhibitory concentration index against 119 Candida glabrata isolates. Synergy was seen in 18% of all isolates and in 4% of fluconazole-resistant isolates at 48 h without evidence of antagonism. This antifungal combination may have utility against this organism.


Assuntos
Antifúngicos/farmacologia , Candida glabrata/efeitos dos fármacos , Peptídeos Cíclicos/farmacologia , Triazóis/farmacologia , Candida glabrata/isolamento & purificação , Candidíase Bucal/microbiologia , Caspofungina , Farmacorresistência Fúngica , Sinergismo Farmacológico , Equinocandinas , Fluconazol/farmacologia , Humanos , Lipopeptídeos , Testes de Sensibilidade Microbiana/métodos
11.
J Clin Microbiol ; 42(12): 5846-8, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15583322

RESUMO

The antifungal susceptibilities of 79 oral Candida glabrata isolates to fluconazole and voriconazole were compared. The MICs at which 90% of the isolates tested were inhibited were 1 microg of voriconazole/ml and 32 microg of fluconazole/ml. Oral C. glabrata isolates for which the fluconazole MICs are elevated are commonly those for which the voriconazole MICs are elevated, but these increases may be transient for voriconazole, as they are for fluconazole.


Assuntos
Antifúngicos/farmacologia , Candida glabrata/efeitos dos fármacos , Candidíase Bucal/microbiologia , Fluconazol/farmacologia , Neoplasias de Cabeça e Pescoço/radioterapia , Pirimidinas/farmacologia , Triazóis/farmacologia , Candida glabrata/isolamento & purificação , Neoplasias de Cabeça e Pescoço/complicações , Humanos , Testes de Sensibilidade Microbiana , Voriconazol
12.
Med Mycol ; 42(5): 479-81, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15552650

RESUMO

Candida glabrata has emerged as a common cause of fungal sepsis in bone marrow transplant patients, particularly those receiving fluconazole prophylaxis. Colonization of the lower GI tract and indwelling catheters have been thought to be the primary sources of systemic infection with Candida. We report on a bone marrow transplant patient who developed Candida glabrata sepsis from pre-existing oral colonization.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Candida glabrata/patogenicidade , Candidíase Bucal/microbiologia , Boca/microbiologia , Sepse/microbiologia , Adulto , Candida glabrata/isolamento & purificação , Humanos , Masculino
13.
Transpl Infect Dis ; 4 Suppl 3: 38-45, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12486791

RESUMO

Invasive fungal infections have been noted in increasing frequency in immunosuppressed patients and may be due to organisms that are less susceptible or frankly resistant to antifungal agents. Recently, standards have been established for testing both yeasts and moulds for susceptibility to antifungal agents. While these tests are increasingly available for clinical use, clinicians are faced with the challenge of whether these tests offer benefit in terms of management and when they should be obtained. In this review, the relevance of these tests is discussed, as are the clinical data, especially for yeasts, that support their use. In addition, the strategy of identifying yeasts to the species level as a means for predicting susceptibility is also discussed. While susceptibility testing of all fungal isolates is not necessary and not recommended, the judicious use of these tests and the role of the mycology laboratory in assisting in management of invasive fungal infection is also evaluated.


Assuntos
Antifúngicos/uso terapêutico , Fungos/efeitos dos fármacos , Testes de Sensibilidade Microbiana/tendências , Antifúngicos/farmacocinética , Candida/classificação , Candida/efeitos dos fármacos , Candidíase Bucal/tratamento farmacológico , Candidíase Bucal/imunologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/patologia , Relação Dose-Resposta a Droga , Farmacorresistência Fúngica , Fluconazol/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana/normas , Micoses/tratamento farmacológico , Micoses/prevenção & controle
14.
J Antimicrob Chemother ; 49(3): 515-24, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11864952

RESUMO

Molecular mechanisms of azole resistance in Candida albicans include alterations in the target enzyme and increased efflux of drug, but the impact of specific treatment regimens on resistance has not been established. A patient with advanced AIDS was enrolled in a longitudinal study to receive continuous oral fluconazole (FLU) 200 mg/day for the treatment of oropharyngeal candidosis (OPC). Oral cultures were obtained at time of enrollment, during episodes of OPC and quarterly for surveillance. The patient had five symptomatic relapses on continuous FLU during 43 months. All OPC episodes were successfully treated with increasing doses of FLU although increased FLU MICs were detected for C. albicans isolates with progression of time. DNA-typing techniques demonstrated that resistance developed in a persistent strain of C. albicans. Both FLU-resistant and isogenic isolates with reduced susceptibility were detected in the same clinical samples through multiple episodes. Analysis of molecular mechanisms of resistance revealed overexpression of MDR and CDR genes encoding efflux pumps (but not ERG11) in isolates with decreased FLU susceptibility. In addition, the presence of the G464S amino acid substitution in their lanosterol demethylase, affecting its affinity for FLU, was also detected. However, other isogenic, but FLU-susceptible isolates recovered from the same samples did not harbour the mutation, indicating microevolution of yeast populations within the oral cavity. In this patient, the continuous antifungal pressure exerted by FLU resulted in development of resistance of multifactorial nature. Despite their clonal origin, different subpopulations of C. albicans demonstrated distinct resistance mechanisms, including concomitant presence and absence of functional point mutations in ERG11 genes.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antifúngicos/uso terapêutico , Candida albicans/genética , Candidíase Bucal/tratamento farmacológico , Fluconazol/uso terapêutico , Doenças Faríngeas/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Candida albicans/efeitos dos fármacos , Candida albicans/isolamento & purificação , Candidíase Bucal/microbiologia , Farmacorresistência Fúngica/genética , Regulação Fúngica da Expressão Gênica , Genes Fúngicos , Heterogeneidade Genética , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Doenças Faríngeas/microbiologia , Estudos Prospectivos
15.
Clin Infect Dis ; 34(1): 7-14, 2002 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-11731939

RESUMO

During the past several decades, there has been a steady increase in the frequency of opportunistic invasive fungal infections (IFIs) in immunocompromised patients. However, there is substantial controversy concerning optimal diagnostic criteria for these IFIs. Therefore, members of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group formed a consensus committee to develop standard definitions for IFIs for clinical research. On the basis of a review of literature and an international consensus, a set of research-oriented definitions for the IFIs most often seen and studied in immunocompromised patients with cancer is proposed. Three levels of probability are proposed: "proven," "probable," and "possible." The definitions are intended for use in the context of clinical and/or epidemiological research, not for clinical decision making.


Assuntos
Aspergilose/complicações , Candidíase/complicações , Transplante de Células-Tronco Hematopoéticas , Hospedeiro Imunocomprometido/imunologia , Neoplasias/complicações , Infecções Oportunistas/complicações , Aspergilose/diagnóstico , Candidíase/diagnóstico , Tomada de Decisões , Humanos , Neoplasias/imunologia , Infecções Oportunistas/imunologia , Infecções Oportunistas/microbiologia
16.
Oral Microbiol Immunol ; 16(5): 270-8, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11555303

RESUMO

This study investigated salivary anticandidal activity and salivary composition in stimulated whole saliva of 18 advanced HIV-infected patients and compared these values to healthy controls. Stimulated whole saliva from HIV-infected patients showed decreased anticandidal activity. The flow rate was reduced by 40% as compared with controls. The saliva flow rate for HIV-infected patients who had recoverable yeast in their saliva was reduced as compared to HIV-infected patients without recoverable yeast. For HIV-infected patients, the saliva concentrations of lactoferrin, secretory IgA and Cl- were increased while the secretion rate of lysozyme, total protein and K+ were reduced. There was no difference in any parameter as a function of taking the antifungal drug fluconazole. There was no association between salivary anticandidal activity and any salivary component. This study shows reduced anticandidal activity and salivary flow rate in HIV-infected patients. These alterations may contribute to their increased incidence of oral candidal infections.


Assuntos
Antifúngicos , Candida albicans , Candidíase Bucal/imunologia , Infecções por HIV/imunologia , Saliva/fisiologia , Adulto , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candida albicans/imunologia , Candidíase Bucal/complicações , Estudos de Casos e Controles , Estudos de Coortes , Contagem de Colônia Microbiana , Eletrólitos/análise , Feminino , Fluconazol/farmacologia , Estruturas Fúngicas , Infecções por HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Saliva/química , Saliva/metabolismo , Saliva/microbiologia , Proteínas e Peptídeos Salivares/análise , Taxa Secretória
17.
Antimicrob Agents Chemother ; 45(10): 2676-84, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11557454

RESUMO

Molecular mechanisms of azole resistance in Candida albicans, including alterations in the target enzyme and increased efflux of drug, have been described, but the epidemiology of the resistance mechanisms has not been established. We have investigated the molecular mechanisms of resistance to azoles in C. albicans strains displaying high-level fluconazole resistance (MICs, > or =64 microg/ml) isolated from human immunodeficiency virus (HIV)-infected patients with oropharyngeal candidiasis. The levels of expression of genes encoding lanosterol 14alpha-demethylase (ERG11) and efflux transporters (MDR1 and CDR) implicated in azole resistance were monitored in matched sets of susceptible and resistant isolates. In addition, ERG11 genes were amplified by PCR, and their nucleotide sequences were determined in order to detect point mutations with a possible effect in the affinity for azoles. The analysis confirmed the multifactorial nature of azole resistance and the prevalence of these mechanisms of resistance in C. albicans clinical isolates exhibiting frank fluconazole resistance, with a predominance of overexpression of genes encoding efflux pumps, detected in 85% of all resistant isolates, being found. Alterations in the target enzyme, including functional amino acid substitutions and overexpression of the gene that encodes the enzyme, were detected in 65 and 35% of the isolates, respectively. Overall, multiple mechanisms of resistance were combined in 75% of the isolates displaying high-level fluconazole resistance. These results may help in the development of new strategies to overcome the problem of resistance as well as new treatments for this condition.


Assuntos
Antifúngicos/farmacologia , Azóis/farmacologia , Candida albicans/efeitos dos fármacos , Infecções por HIV/microbiologia , Proteínas Proto-Oncogênicas , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Candida albicans/enzimologia , Candida albicans/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Proteínas de Ligação a DNA/metabolismo , Resistência Microbiana a Medicamentos/genética , Fluconazol/farmacologia , Frequência do Gene , Humanos , Testes de Sensibilidade Microbiana , Mutação , Oxirredutases/genética , Oxirredutases/metabolismo , Proteína 1 Parceira de Translocação de RUNX1 , Esterol 14-Desmetilase , Fatores de Transcrição/metabolismo
18.
Artigo em Inglês | MEDLINE | ID: mdl-11402278

RESUMO

Candida dubliniensis is a recently described species that has been shown to cause oropharyngeal candidiasis in patients with HIV. We present a detailed evaluation of a patient undergoing head and neck radiation for oral cancer who developed oropharyngeal candidiasis from a mixed infection of C dubliniensis and Candida albicans. To our knowledge, this is the first described case of C dubliniensis contributing to oropharyngeal candidiasis in this patient population.


Assuntos
Candida/classificação , Candidíase Bucal/microbiologia , Candidíase/microbiologia , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias Bucais/radioterapia , Orofaringe/microbiologia , Doenças Faríngeas/microbiologia , Lesões por Radiação/microbiologia , Adulto , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Candida/genética , Candida/crescimento & desenvolvimento , Candida albicans/crescimento & desenvolvimento , Carcinoma de Células Escamosas/secundário , Compostos Cromogênicos , DNA Fúngico/análise , Feminino , Fluconazol/administração & dosagem , Fluconazol/uso terapêutico , Neoplasias de Cabeça e Pescoço/secundário , Humanos , Cariotipagem , Metástase Linfática/radioterapia
19.
J Clin Microbiol ; 39(2): 514-8, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11158099

RESUMO

Fungi have become increasingly important causes of nosocomial bloodstream infections. The major cause of nosocomial fungemia has been Candida spp, but increasingly molds and other yeasts have caused disease. Exophiala jeanselmei and members of the genus Rhinocladiella are dematiaceous moulds, which have been infrequently associated with systemic infection and have not been described as causes of fungemia. In this paper, the occurrence of 23 cases of fungemia due to these organisms over a 10-month period is reported and the clinical characteristics of patients and outcomes are described. The majority of patients were immunosuppressed; 21 of 23 (91%) had received blood products and 78% had a central venous catheter. All patients had at least one manifestation of fever, but only one patient had signs or symptoms suggesting deep-seated infection. Antifungal therapy was given to 19 of the 23 patients; of those who did not receive therapy, 3 died prior to the culture result and 1 had been discharged without therapy. Antifungal susceptibility of the organisms showed activity of amphotericin B, itraconazole, and the new triazole antifungals voriconazole and posaconazole. E. jeanselmei and Rhinocladiella species are potential causes of nosocomial fungemia and may be associated with systemic infection.


Assuntos
Ascomicetos/isolamento & purificação , Infecção Hospitalar/microbiologia , Fungemia/diagnóstico , Micoses/diagnóstico , Adolescente , Adulto , Idoso , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Ascomicetos/classificação , Cateterismo Venoso Central/efeitos adversos , Criança , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Feminino , Fungemia/tratamento farmacológico , Fungemia/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Micoses/tratamento farmacológico , Micoses/etiologia , Resultado do Tratamento
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