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Antimicrobial Agents and Chemotherapy, October 2002, p. 3323-3326, Vol. 46, No. 10
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.10.3323-3326.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

In Vitro Synergistic Interaction between Amphotericin B and Pentamidine against Scedosporium prolificans

Javier Afeltra,1 Eric Dannaoui,1 Jacques F. G. M. Meis,2 Juan L. Rodriguez-Tudela,3 Paul E. Verweij,1* and and Eurofung Network{dagger}

Department of Medical Microbiology, University Medical Center Nijmegen,1 Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands,2 Unidad de Micología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain3

Received 5 February 2002/ Returned for modification 29 May 2002/ Accepted 11 July 2002

To develop new approaches for the treatment of invasive infections caused by Scedosporium prolificans, the in vitro interaction between amphotericin B and pentamidine against 30 clinical isolates was evaluated using a checkerboard microdilution method based on the National Committee for Clinical Laboratory Standards M38-P guidelines. The interaction between the drugs was analyzed using fractional inhibitory concentration index (FICI) analysis and response surface modeling. Amphotericin B alone was inactive against all the isolates. The geometric mean MIC for pentamidine was 57 µg/ml (range, 8 to 256 µg/ml; MIC at which 50% of the isolates tested were inhibited [MIC50], 64 µg/ml; MIC90, 128 µg/ml). The combination was synergistic against 28 of 30 isolates (93.3%) by FICI analysis and 30 of 30 (100%) by response surface modeling analysis. Antagonism was not observed.

* Corresponding author. Mailing address: Department of Medical Microbiology, University Medical Center Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Phone: 31-24-3614356. Fax: 31-24-3540216. E-mail: p.verweij{at}mmb.azn.nl.

{dagger} The Eurofung Network consists of the following participants: Emmanuel Roilides, coordinator, and Nicos Maglaveras, Aristotle University, Thessaloniki, Greece; Tore Abrahamsen and Peter Gaustad, Rikshospitalet National Hospital, Oslo, Norway; David W. Denning, University of Manchester, Manchester, United Kingdom; Paul E. Verweij and Jacques F. G. M. Meis, University of Nijmegen, Nijmegen, The Netherlands; Juan L. Rodriguez-Tudela, Instituto de Salud Carlos III, Madrid, Spain; and George Petrikkos, Athens University, Athens, Greece.

Antimicrobial Agents and Chemotherapy, October 2002, p. 3323-3326, Vol. 46, No. 10
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.10.3323-3326.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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