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1.
Mycopathologia ; 183(2): 359-370, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28994001

RESUMO

The checkerboard broth microdilution assay (BMD) is the most frequently used method for the in vitro evaluation of drug combinations. However, its use to evaluate the effect of antifungal drugs on filamentous fungi is sometimes associated with endpoint-reading difficulties, and different degrees of interaction are assigned to the same drug combination. We evaluated combinations of the azoles, itraconazole, posaconazole, and voriconazole, with the echinocandins, anidulafungin, caspofungin, and micafungin, against 15 itraconazole-resistant Aspergillus fumigatus clinical strains via the checkerboard BMD and Etest assay. Readings after 24 and 48 h, considering the two reading endpoints, the minimum inhibitory concentration (MIC) and minimum effective concentration (MEC), were performed for both methods. Our results showed that the correlation coefficients between the BMD and Etest methods were quite diverse to the drug combinations tested. The highest correlation coefficients of the Etest with the BMD assays (MEC and MIC reading) were the Etest-MIC reading at 24 h and the Etest-MEC reading at 48 h. Improvements in experimental conditions may increase the correlation between the two methods and ensure that Etest assay can be safely used in the evaluation of antifungal combinations against Aspergillus species.


Assuntos
Antifúngicos/farmacologia , Aspergillus fumigatus/efeitos dos fármacos , Farmacorresistência Fúngica , Itraconazol/farmacologia , Testes de Sensibilidade Microbiana/métodos , Aspergilose/microbiologia , Aspergillus fumigatus/isolamento & purificação , Interações Medicamentosas , Equinocandinas/farmacologia , Humanos
2.
Mycopathologia ; 181(9-10): 663-70, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27318852

RESUMO

The naturally high minimum inhibitory concentration exhibited by echinocandins against Candida parapsilosis has been known since the first introduction of these antifungal agents. Despite this awareness, clinical failures have not been reported; consequently, the resistance of C. parapsilosis to echinocandins remains unexplored. We exposed 30 isolates of C. parapsilosis to echinocandins (caspofungin, micafungin, and anidulafungin) in vitro and studied the effects of this exposure. After 60 exposures, 80, 67, and 60 % of the isolates changed from susceptible to non-susceptible to caspofungin, micafungin, and anidulafungin, respectively. In addition, four strains exhibited cross-resistance to all three echinocandins. Based on the M27-A3 (CLSI, 2008) and M27-S4 (CLSI, 2012) techniques, the susceptibility of the resistant strains to other antifungal agents was assayed. All of the tested echinocandin-resistant strains were susceptible to amphotericin B, and the resistance rate to fluconazole, voriconazole, and flucytosine was 73.3, 43.3, and 20 %, respectively. The exposure of C. parapsilosis to the three echinocandins generated cross-resistant strains and an unexpected in vitro resistance to azoles and flucytosine.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Equinocandinas/farmacologia , Azóis/farmacologia , Candidíase/microbiologia , Farmacorresistência Fúngica , Humanos , Testes de Sensibilidade Microbiana
3.
Rev Iberoam Micol ; 36(1): 44-47, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30691952

RESUMO

BACKGROUND: Candida parapsilosis may acquire resistance to echinocandins, a fact that prompts the search for new therapeutic options. AIMS: The present study aimed to evaluate the in vitro activity of antifungal agents, alone and in combination, against four groups of C. parapsilosis strains: (1) echinocandin-susceptible (ES) clinical isolates (MIC ≤ 2µg/ml), (2) anidulafungin-resistant strains (MIC ≥ 8µg/ml), (3) caspofungin-resistant strains (MIC ≥ 8µg/ml), and (4) micafungin-resistant strains (MIC ≥ 8µg/ml). METHODS: Antifungal interactions were evaluated by a checkerboard micro-dilution method. The determination of the MIC to each drug for every isolate according to the Clinical and Laboratory Standards Institute documents M27 (2017) and M60 (2017) was also done. RESULTS: The echinocandins-resistant (ER) strains showed higher MICs to the tested antifungals than the ES strains, except for amphotericin B, for which the ER groups remained susceptible. CONCLUSIONS: Most combinations showed indifferent interactions. The use of monotherapy still seems to be the best option. As resistance to echinocandins is an emergent phenomenon, further studies are required to provide clearer information on the susceptibility differences between strains to these antifungal agents.


Assuntos
Antifúngicos/farmacologia , Candida parapsilosis/efeitos dos fármacos , Equinocandinas/farmacologia , Candida parapsilosis/classificação , Farmacorresistência Fúngica , Quimioterapia Combinada , Testes de Sensibilidade Microbiana
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