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Antimicrobial Agents and Chemotherapy, January 2002, p. 62-68, Vol. 46, No. 1
0066-4804/01/$04.00+0     DOI: 10.1128/AAC.46.1.62-68.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

In Vitro Activities of New and Conventional Antifungal Agents against Clinical Scedosporium Isolates

Joseph Meletiadis,1 Jacques F. G. M. Meis,2 Johan W. Mouton,2 Juan Luis Rodriquez-Tudela,3 J. Peter Donnelly,4 Paul E. Verweij,1* and the EUROFUNG Network {dagger}

Departments of Medical Microbiology,1 Department of Medical Microbiology and Regional Public Health Laboratory, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands,2 Unidad de Micología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda (Madrid), Spain,3 Hematology, University Medical Center Nijmegen4

Received 5 April 2001/ Returned for modification 8 May 2001/ Accepted 27 September 2001

The susceptibilities of 13 clinical isolates of Scedosporium apiospermum and 55 clinical isolates of S. prolificans to new and conventional drugs belonging to three different classes of antifungal agents, the azoles (miconazole, itraconazole, voriconazole, UR-9825, posaconazole), the polyenes (amphotericin B, nystatin and liposomal nystatin), and allylamines (terbinafine), were studied by use of proposed standard M38-P of NCCLS. Low growth-inhibitory antifungal activities were found in vitro for most of the drugs tested against S. prolificans isolates, with the MICs at which 90% of isolates are inhibited (MIC90s) being >8 µg/ml; the MIC90s of voriconazole and UR-9825, however, were 4 µg/ml. S. apiospermum isolates were more susceptible in vitro, with the highest activity exhibited by voriconazole (MIC90s, 0.5 µg/ml), followed by miconazole (MIC90s, 1 µg/ml), UR-9825 and posaconazole (MIC90s, 2 µg/ml), and itraconazole (MIC90s, 4 µg/ml). The MICs of terbinafine, amphotericin B, and the two formulations of nystatin (for which no statistically significant differences in antifungal activities were found for the two species) for S. apiospermum isolates were high. Cross-resistance was observed among all the azoles except posaconazole and among all the polyenes except the lipid formulation. A distribution analysis was performed with the MICs of each drug and for each species. Bimodal and skewed MIC distributions were obtained, and cutoffs indicating the borders of different MIC subpopulations of the distributions were determined on the basis of the normal plot technique. These cutoffs were in many cases reproducible between 48 and 72 h.

* Corresponding author. Mailing address: Department of Medical Microbiology, University Medical Center Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Phone: 31-24-3619627. Fax: 31-24-3540216. E-mail: p.verweij{at}mmb.azn.nl.

{dagger} The EUROFUNG Network (EC-TMR-EUROFUNG network; ERBFMXR-CT970145) 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, January 2002, p. 62-68, Vol. 46, No. 1
0066-4804/01/$04.00+0     DOI: 10.1128/AAC.46.1.62-68.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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