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Antimicrobial Agents and Chemotherapy, May 2001, p. 1456-1462, Vol. 45, No. 5
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.5.1456-1462.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Susceptibility Testing of Aspergillus flavus: Inoculum Dependence with Itraconazole and Lack of Correlation between Susceptibility to Amphotericin B In Vitro and Outcome In Vivo

J. Mosquera,1 P. A. Warn,1 J. Morrissey,1 C. B. Moore,2 C. Gil-Lamaignere,3 and D. W. Denning1,4,*

Section of Infectious Diseases, Department of Medicine, Hope Hospital, University of Manchester,1 and Department of Microbiology, Salford Royal Hospital NHS Trust,2 Salford, Manchester M6 8HD, and Department of Infectious Diseases and Tropical Medicine, North Manchester General Hospital, Manchester M8 6RB,4 United Kingdom; and 3rd Department of Pediatrics, Hippokration Hospital, Aristotle University of Thessaloniki, GR-546 42 Thessaloniki, Greece3

Received 28 June 2000/Returned for modification 8 August 2000/Accepted 30 January 2001

We have attempted to validate in Aspergillus flavus the main in vitro methodologies that have been used to detect resistance in Aspergillus fumigatus. We developed a murine model with two A. flavus isolates, one that was apparently resistant in vitro to amphotericin B (AFL5) and another that was resistant to itraconazole (AFL8). No correlation was found for amphotericin B in AFL5, since the in vivo response was compatible with a susceptible isolate. Modification of the in vitro susceptibility test methodology for amphotericin B was unsuccessful. Although AFL8 was apparently resistant to itraconazole in vitro, it was found to be susceptible in vivo. Additional in vitro work has detected weaknesses in the in vitro susceptibility methodology validated for A. fumigatus when applied to A. flavus. The principal problems are that changes in the inoculum have a large effect on the MICs of itraconazole for some A. flavus strains and that a trailing end point and spore sediment often appear when an inoculum with a higher colony count is used. We propose a modified method using a final inoculum of 2.5 × 104 CFU per ml of RPMI 1640 medium with 2% glucose buffered to pH 7.0 in a microtiter format, incubated for 48 h with no growth end point. Validation of this methodology requires one or more itraconazole-resistant A. flavus isolates, which have yet to be identified.

* Corresponding author. Mailing address: Department of Infectious Diseases and Tropical Medicine, North Manchester General Hospital, Delaunays Road, Manchester M8 6RB, United Kingdom. Phone: 0161 720 2734. Fax: 0161 720 2732. E-mail: ddenning{at}man.ac.uk.

Antimicrobial Agents and Chemotherapy, May 2001, p. 1456-1462, Vol. 45, No. 5
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.5.1456-1462.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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