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Clin Microbiol Infect. 2001 Jan;7(1):11-6.

In vitro activity of a new echinocandin, LY303366, and comparison with fluconazole, flucytosine and amphotericin B against Candida species.

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1
Department of Microbiology, Hope Hospital, Salford, UK.

Abstract

OBJECTIVE:

To investigate the in vitro activity of LY303366 (LY) against Candida isolates comprising nine different species and comparison with fluconazole (FLU), flucytosine (5FC) and amphotericin B (AMB).

METHODS:

The method used was a microtitre modification of the NCCLS M27-A accepted standard using either RPMI-1640 with 2% glucose (5FC and FLU) or antibiotic medium 3 with 2% glucose (LY and AMB). The minimum inhibitory concentration (MIC) was the lowest drug concentration that reduced growth by 80% compared with the drug-free control. Minimum fungicidal concentrations (MFCs; 99% kill) were also determined for all isolates for LY and AMB.

RESULTS:

Overall, 58 of 105 (55.2%) isolates were resistant to FLU (MIC < or = 16 mg/L). There was no relationship between FLU and LY MICs for C. albicans or non-albicans species. For all isolates, geometric mean (GM) MIC values and ranges (in mg/L) were: LY 0.011 and < or = 0.001-16, FLU 8.72 and < or = 0.125- > 128, 5FC 0.393 and < or = 0.03- > 32, AMB 0.046 and 0.008-0.125. Differences in susceptibility to LY were seen: C. parapsilosis (n = 12, GM 0.4 and range 0.125-16) and C. guilliermondii (n = 8, GM 0.46 and range 0.25-1) were both found to be significantly less susceptible to LY than all other species (P < or = 0.05). For all isolates, geometric mean MFC values and ranges (in mg/L) were: LY 0.032 and 0.002-16, AMB 0.143 and 0.03-2. The MFC value was the same as or only one drug dilution higher than the MIC value for 69.5% and 48.6% of isolates tested for LY and AMB, respectively. Tolerance was described in 13.3% and 5.7% of isolates for LY and AMB, respectively. A reproducibility study performed on 20% of the isolates showed that 90.5%, 100%, 95.2% and 100% of isolates retested were the same or within one well of the original MIC value for LY, FLU, 5FC and AMB, respectively.

CONCLUSIONS:

LY303366 shows promising antifungal activity in vitro and warrants further in vivo investigation.

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