Journal Article

<i>In vitro</i> activity of a new triazole BAL4815, the active component of BAL8557 (the water-soluble prodrug), against <i>Aspergillus</i> spp.

Peter A. Warn, Andrew Sharp and David W. Denning

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 57, issue 1, pages 135-138
Published in print January 2006 | ISSN: 0305-7453
Published online November 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dki399
In vitro activity of a new triazole BAL4815, the active component of BAL8557 (the water-soluble prodrug), against Aspergillus spp.

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Objectives: BAL4815 is the active component of the antifungal triazole agent BAL8557 (the water-soluble prodrug). We compared the in vitro activity of BAL4815 with that of itraconazole, voriconazole, caspofungin and amphotericin B against 118 isolates of Aspergillus comprising four different species (fumigatus, terreus, flavus and niger); the isolates were pre-selected to include 16 isolates demonstrating in vitro resistance to other agents.

Methods: Susceptibilities were determined for BAL4815, amphotericin B, itraconazole and voriconazole using the microdilution plate modification of the NCCLS M38-A method with RPMI 1640 buffered to pH 7.0 with MOPS; for caspofungin the method was modified using incubation in a gas mixture of 1% O2/5% CO2/94% N2 to aid reading. MFCs (≥99% kill) were also determined for all drugs other than caspofungin.

Results: For all isolates, geometric mean (GM) MIC values and ranges (in mg/L) were: BAL4815, 0.620 and 0.125–2.0; itraconazole, 0.399 and 0.063–>8.0; voriconazole, 0.347 and 0.125–8.0; caspofungin, 0.341 and 0.125–4.0; amphotericin B, 0.452 and 0.06–4.0. No significant differences in susceptibility to BAL4815 were seen between species and in contrast to itraconazole no isolates demonstrated MICs >2.0 mg/L. For all isolates, GM MFC values and ranges (in mg/L) were: BAL4815, 1.68 and 0.25–>8.0; itraconazole, 1.78 and 0.06–>8.0; voriconazole, 1.09 and 0.25–>8.0; amphotericin B, 0.98 and 0.25–>4.0.

Conclusions: BAL4815 demonstrated promising antifungal activity against all four Aspergillus species in vitro including strains resistant to itraconazole, caspofungin or amphotericin B.

Keywords: antifungal susceptibility; itraconazole; voriconazole; caspofungin; amphotericin B

Journal Article.  2361 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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