JAC Advance Access originally published online on November 10, 2005
Journal of Antimicrobial Chemotherapy 2006 57(1):135-138; doi:10.1093/jac/dki399
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In vitro activity of a new triazole BAL4815, the active component of BAL8557 (the water-soluble prodrug), against Aspergillus spp.
1 School of Medicine, 1.800 Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK; 2 Wythenshawe Hospital, Southmoor Road, Manchester M23 9PL, UK
Received 20 July 2005; returned 19 August 2005; revised 19 September 2005; accepted 5 October 2005
* Corresponding author. Tel: +44-161-2753918; Fax: +44-161-2755656; E-mail: peter.warn{at}manchester.ac.uk
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
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