1 Departamento de Microbiología, ACIA, PO Box 10178, E-08080 Barcelona; 2 Departamento de Inmunología, Microbiología y Parasitología, Facultad de Medicina, Universidad del País Vasco, Bilbao; 3 Servicio de Microbiología, Hospital Vall d'Hebrón, Barcelona; 4 Servicio de Microbiología, Hospital La Inmaculada, Huércal-Overa, Almería, Spain; 5 Schering-Plough Research Institute, Kenilworth, NJ, USA; 6 Hospital de Pediatría Pablo Garrahan, Buenos Aires, Argentina
Received 3 March 2004; returned 22 March 2004; revised 21 November 2004; accepted 15 December 2004
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Abstract |
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Materials and methods: A microdilution method (M27-A2) was used with 331 clinical yeast isolates.
Results: The geometric mean MICs of posaconazole, fluconazole and amphotericin B were 0.16, 0.91 and 0.15 mg/L, respectively. Posaconazole was markedly more active than fluconazole and was active against 9/11 fluconazole-resistant Candida albicans, and five Candida glabrata had an MIC of posaconazole of 16 mg/L.
Conclusions: These data indicate that posaconazole is a potentially effective antifungal agent for the treatment of mycoses caused by yeasts.
Keywords: susceptibility , opportunistic , Candida
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Introduction |
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The purpose of this study was to compare the in vitro antifungal activity of posaconazole with that of fluconazole and amphotericin B gainst a collection of 331 clinically significant yeasts using the standardized microdilution method as described in the NCCLS document M27-A2.27
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Materials and methods |
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All isolates were stored in sterile distilled water. Before testing, the isolates were subcultured on Sabouraud glucose agar (Biolife, Milan, Italy) at 35°C for 24 h to ensure the inoculum's purity and viability. Antifungal agents were obtained from their respective manufacturers: posaconazole, Schering-Plough Research Institute (Kenilworth, NJ, USA); fluconazole, Pfizer (Sandwich, UK); and amphotericin B, Bristol-Myers Squibb (Princeton, NJ, USA). Amphotericin B and posaconazole were solubilized in DMSO (UVASOL DMSO; Merck, Darmstadt, Germany), and fluconazole was solubilized in water.
Susceptibility testing was carried out according to the NCCLS document M27-A2.27
RPMI 1640 (with glutamine and without bicarbonate) buffered with MOPS (0.165 M) (Sigma Chemical Co., St Louis, MO, USA) was used. The pH of RPMI 1640 was adjusted to pH 7.0 at 25°C using sodium hydroxide (Panreac, Madrid, Spain). The medium was filter-sterilized (Steritop-GP Units, Millipore, Billerica, MA, USA) and stored at 28°C. Antifungal drug concentrations ranged from 0.25 to 256 mg/L for fluconazole, and 0.01616 mg/L for posaconazole and amphotericin B. A strain was considered resistant to fluconazole and amphotericin B if the MICs were 64 and > 1 mg/L, respectively. A strain was considered to be fluconazole-susceptible-dose-dependent when the MIC was 1632 mg/L. The MIC50 s and MIC90 s were calculated as the concentrations of antifungal that were able to inhibit 50% and 90% of the isolates, respectively.
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Results |
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Discussion |
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References |
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