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JAC Advance Access originally published online on March 24, 2004
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Journal of Antimicrobial Chemotherapy (2004) 53, 743-749
© 2004 The British Society for Antimicrobial Chemotherapy

Effect of hypoxic conditions on in vitro susceptibility testing of amphotericin B, itraconazole and micafungin against Aspergillus and Candida

Peter A. Warn1,*, A. Sharp1, J. Guinea1 and David W. Denning1,2

1 School of Medicine, University of Manchester, Hope Hospital, Salford M6 8HD; 2 Wythenshawe Hospital, Southmoor Road, Manchester M23 9PL, UK

Received 20 March 2003; returned 18 April 2003; revised 20 January 2004; accepted 27 January 2004

Objectives: The aim of this study was to investigate the effect of hypoxic conditions on in vitro susceptibility testing of amphotericin B, itraconazole and micafungin against Aspergillus (four species) and Candida (six species).

Methods: In vitro susceptibility tests were set up according to NCCLS M27-A2 and M38-A recommendations, but incubation atmospheres were either air plus 5% CO2, 1% oxygen/5% CO2/94% nitrogen or 0.25% oxygen/5% CO2/94.75% nitrogen.

Results: In all Aspergillus species, the MIC of amphotericin B was reduced but the MFC remained unaltered with reduced oxygen. The MICs and MFCs of itraconazole and micafungin were unaltered in hypoxic conditions but interpretation of the MIC was much simpler for micafungin with 1% and 0.25% oxygen. Against Candida, conditions modelling hypoxia had little effect on the MICs and MFCs of any of the agents.

Conclusions: This simple adaptation of susceptibility testing may have important consequences for understanding how antifungal drugs work and for endpoint reading.

Keywords: antifungals, hypoxia, susceptibility tests

* Corresponding author. Tel: +44-161-206-4420; Fax: +44-161-206-1495; E-mail: pwarn{at}fs1.ho.man.ac.uk


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