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1.
AIDS Res Treat ; 2012: 262471, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22970352

RESUMO

The impact of antiretroviral therapy (ART) on opportunistic conditions in HIV patients continues to evolve. We specifically studied the changing epidemiology of oropharyngeal candidiasis (OPC) in 215 HIV/AIDS patients. Status of yeast colonization was assessed from oral rinse samples, and preliminary yeast identification was made using CHROMagar Candida and confirmed with standard microbiological techniques and/or molecular sequencing. Susceptibility to fluconazole was determined by CHROMagar Candida agar dilution screening and CLSI broth microdilution. 176 (82%) patients were colonized and 59 (27%) patients had symptomatic OPC. Candida albicans was the most prevalent species, though C. glabrata and C. dubliniensis were detected in 29% of isolates. Decreased fluconazole susceptibility occurred in 10% of isolates. Previous ART reduced the risk of OPC, while smoking increased the risk of colonization. Oral yeast colonization and symptomatic infection remain common even with advances in HIV therapy. C. albicans is the most common species, but other yeasts are prevalent and may have decreased susceptibility to fluconazole.

2.
J Antimicrob Chemother ; 67(4): 970-6, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22240402

RESUMO

OBJECTIVES: Amphotericin B inhalation powder (ABIP) is a novel dry-powder amphotericin B formulation that is directly delivered to the lung, resulting in elevated lung tissue drug concentrations of this polyene. We evaluated the prophylactic efficacy of single dose administration of ABIP in a guinea pig model of invasive pulmonary aspergillosis. METHODS: Guinea pigs were immunosuppressed with cyclophosphamide and cortisone acetate and challenged with Aspergillus fumigatus conidia in an aerosol chamber. Guinea pigs received prophylaxis with a single inhaled dose of ABIP at 0.05, 0.5, 4 or 10 mg/kg administered 24 h prior to infection. Treatment with oral voriconazole at doses of 5 or 10 mg/kg twice daily beginning 24 h post-challenge served as the positive control. RESULTS: Improvements in survival were observed with ABIP prophylaxis. A single inhaled dose of 4 mg/kg ABIP and treatment with 5 mg/kg voriconazole both improved median and percentage survival compared with untreated controls. In addition, pulmonary fungal burden, as assessed by cfu, quantitative PCR and galactomannan, was also reduced in a dose-dependent fashion with ABIP prophylaxis as well as with both doses of voriconazole treatment. CONCLUSIONS: Single-dose prophylaxis with inhaled ABIP as prophylaxis demonstrated a significant survival advantage and reductions in pulmonary fungal burden in this model of invasive pulmonary aspergillosis. Optimization of the dose and dosing frequency of ABIP dose may help to further enhance the anti-Aspergillus activity of this novel amphotericin B formulation.


Assuntos
Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Aspergillus fumigatus/patogenicidade , Quimioprevenção/métodos , Aspergilose Pulmonar Invasiva/prevenção & controle , Administração por Inalação , Animais , Aspergillus fumigatus/efeitos dos fármacos , Contagem de Colônia Microbiana , Cortisona/administração & dosagem , Cortisona/análogos & derivados , Ciclofosfamida/administração & dosagem , Modelos Animais de Doenças , Cobaias , Imunossupressores/administração & dosagem , Pulmão/microbiologia , Masculino , Pirimidinas/administração & dosagem , Análise de Sobrevida , Triazóis/administração & dosagem , Voriconazol
3.
Med Mycol ; 48(3): 557-60, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20370365

RESUMO

We report a case of fluconazole-resistant oropharyngeal colonization caused by a strain of Candida glabrata that rapidly regained susceptibility once prophylaxis with this agent was discontinued and echinocandin therapy was initiated. Isolates collected before and after discontinuation of fluconazole were confirmed to be isogenic by RAPD analysis. Transcription analysis demonstrated constitutive expression of genes encoding efflux pumps in the isolate recovered on fluconazole prophylaxis and transient expression in those isolates collected after fluconazole was discontinued.


Assuntos
Antifúngicos/uso terapêutico , Candida glabrata/efeitos dos fármacos , Quimioprevenção/métodos , Farmacorresistência Fúngica , Fluconazol/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Antifúngicos/farmacologia , Candida glabrata/classificação , Candida glabrata/genética , Candida glabrata/isolamento & purificação , Candidíase/microbiologia , Portador Sadio/microbiologia , Impressões Digitais de DNA , DNA Fúngico/genética , Equinocandinas/uso terapêutico , Fluconazol/farmacologia , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Tipagem Micológica , Orofaringe/microbiologia , Técnica de Amplificação ao Acaso de DNA Polimórfico
4.
Antimicrob Agents Chemother ; 53(1): 309-11, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18955539

RESUMO

We measured antifungal activity against 128 cryptococcal isolates (86 of C. neoformans and 42 of C. gattii) to determine if differences in serotype susceptibility exist. Contrary to previous results, we found no serotype susceptibility differences. Isavuconazole, posaconazole, and voriconazole demonstrated excellent potency against each isolate and serotype, including isolates with reduced fluconazole susceptibilities.


Assuntos
Antifúngicos/farmacologia , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus/efeitos dos fármacos , Cryptococcus/classificação , Cryptococcus neoformans/classificação , Fluconazol/farmacologia , Testes de Sensibilidade Microbiana , Nitrilas/farmacologia , Piridinas/farmacologia , Pirimidinas/farmacologia , Sorotipagem , Triazóis/farmacologia , Voriconazol
5.
Antimicrob Agents Chemother ; 52(10): 3783-5, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18676885

RESUMO

We report a case of Candida glabrata invasive candidiasis that developed reduced susceptibility to caspofungin during prolonged therapy. Pre- and posttreatment isolates were confirmed to be isogenic, and sequencing of hot spots known to confer echinocandin resistance revealed an F659V substitution within the FKS2 region of the glucan synthase complex.


Assuntos
Antifúngicos/farmacologia , Candida glabrata/efeitos dos fármacos , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Equinocandinas/farmacologia , Adulto , Substituição de Aminoácidos , Sequência de Bases , Candida glabrata/enzimologia , Candida glabrata/genética , Caspofungina , Primers do DNA/genética , DNA Fúngico/genética , Farmacorresistência Fúngica/genética , Genes Fúngicos , Glucosiltransferases/genética , Humanos , Lipopeptídeos
6.
Antimicrob Agents Chemother ; 52(8): 2959-61, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18559645

RESUMO

We compared Etest with broth microdilution testing for isavuconazole activity against 92 Cryptococcus isolates. A 97.8% agreement was found between these methods, without major discrepancies (>2-well dilution difference). Our findings support the use of the Etest methodology as a reliable method for the determination of MICs against Cryptococcus spp.


Assuntos
Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodos , Nitrilas/farmacologia , Piridinas/farmacologia , Triazóis/farmacologia , Antifúngicos/farmacologia , Reprodutibilidade dos Testes , Especificidade da Espécie
7.
Antimicrob Agents Chemother ; 52(7): 2593-8, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18474582

RESUMO

Early diagnosis of invasive pulmonary aspergillosis is problematic in some patient groups due to the lack of rapid, sensitive, specific, and reliable diagnostic tests. Fungal burden and therapeutic efficacy were assessed by survival, quantitative culture (CFU counts), galactomannan enzyme immunoassay (GM-EIA), and quantitative PCR (qPCR) in a new guinea pig model of invasive pulmonary aspergillosis using an aerosol challenge. At 1 day postinfection, qPCR determined that the pulmonary fungal burden was 2 log(10) higher than that determined by CFU counting and increased significantly (P < 0.03) over time. In contrast, the tissue burden assessed by CFU counting did not rise over the course of the study. Therapy with the antifungal drug voriconazole produced statistically significant decreases in pulmonary fungal burden, as detected by CFU counting (P < 0.02), qPCR, and GM-EIA (both P < 0.0002). Daily assessment of the progression of fungal infection in serum was performed by qPCR and GM-EIA. GM-EIA demonstrated a statistically significant reduction in the fungal load on days 6 and 7 in voriconazole-treated animals compared to time-matched controls (P < 0.02). Confirmation of fungal tissue burden by two or more methods should provide a more precise account of the burden, allowing improved assessment of diagnostic and therapeutic strategies in invasive pulmonary aspergillosis.


Assuntos
Aspergilose/diagnóstico , Aspergillus fumigatus/isolamento & purificação , Pneumopatias Fúngicas/diagnóstico , Animais , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Aspergillus fumigatus/química , Aspergillus fumigatus/genética , Sequência de Bases , Contagem de Colônia Microbiana , Primers do DNA/genética , DNA Fúngico/genética , Modelos Animais de Doenças , Cobaias , Humanos , Técnicas Imunoenzimáticas/métodos , Pulmão/microbiologia , Pulmão/patologia , Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/microbiologia , Masculino , Mananas/análise , Micologia/métodos , Reação em Cadeia da Polimerase/métodos , Pirimidinas/uso terapêutico , Triazóis/uso terapêutico , Voriconazol
9.
Antimicrob Agents Chemother ; 50(10): 3501-3, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17005844

RESUMO

Evaluating new therapeutic agents for invasive aspergillosis requires animal models that are reproducible among different laboratories. We therefore evaluated a murine model of aerosol infection in two independent laboratories and found a high level of both intra- and interlaboratory reproducibility of survival, fungal burden over time, and the efficacy of liposomal amphotericin B.


Assuntos
Aspergilose , Aspergillus fumigatus/patogenicidade , Modelos Animais de Doenças , Pneumopatias Fúngicas , Anfotericina B/uso terapêutico , Animais , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Aspergilose/mortalidade , Aspergillus fumigatus/isolamento & purificação , Humanos , Lipossomos , Pulmão/microbiologia , Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/microbiologia , Pneumopatias Fúngicas/mortalidade , Camundongos , Reprodutibilidade dos Testes , Resultado do Tratamento
10.
Antimicrob Agents Chemother ; 49(11): 4751-3, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16251321

RESUMO

Antagonistic effects of combination therapy using amphotericin B (AmB) with agents which block ergosterol synthesis are a concern. Terbinafine was evaluated with AmB to assess antagonism or synergy in a rabbit model of invasive aspergillosis. Terbinafine had relatively little activity but did not demonstrate antagonism against AmB in our model.


Assuntos
Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Aspergilose/tratamento farmacológico , Naftalenos/administração & dosagem , Animais , Aspergillus fumigatus/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Testes de Sensibilidade Microbiana , Coelhos , Terbinafina
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