Nationwide Survey of In Vitro Activity of Antifungal Agents against Clinical Aspergillus fumigatus Isolates Cultured between 1945 and 1998 in The Netherlands.



A nationwide survey of in vitro activity of antifungal agents against 190 clinical Aspergillus fumigatus isolates from The Netherlands was performed in order to establish the prevalence of resistance and to compare the development of resistance in relation to availability of the drug for therapeutic purposes. The isolates included 70 from the collection of the Centraalbureau voor Schimmelcultures (CBS) which were cultured from patients between 1945 and 1990. The remaining isolates were cultured from patients between 1990 and 1998 and obtained from the collections of 15 Hospitals including 5 of 8 tertiary care university hospitals in The Netherlands. The in vitro activity of amphotericin B (AB), itraconazole (ITZ), voriconazole (VCZ), UR9825 (UR), terbinafine (TB), and LY303366 (LY) was determined by the proposed NCCLS broth microdilution method and MICs were read after 24 and 48 h of incubation. An ITZ susceptible (AF71, MIC 0.25 mg/l) and -resistant (AF90, MIC >64 mg/l) A. fumigatus isolate was included in each test. The geometric mean MIC at 24 h (range) was 2.0 mg/l (1-4) of AB; 1.0 mg/l (0.5-64) of ITZ; 0.17 mg/l (0.06-0.5) of VCZ; 0.16 mg/l (0.06-0.5) of UR; 1.72 mg/l (0.13-4) of TB and 0.12 mg/l (0.03-0.25) of LY. Isolates with high MIC values were not found among those from the CBS culture collection. High MIC values (>32 mg/l) of ITZ were found in 3 A. fumigatus isolates (1.6%), but these isolates were susceptible in vitro to VCZ and UR. The 3 isolates were cultured from bronchoalveolar lavage fluid samples from one lung transplant recipient during treatment with ITZ. For all drugs the mean MIC before and after introduction of the antifungal agent was not significantly different. Provided that resistance is maintained during storage, our results indicate that natural resistance of A. fumigatus to antifungal agents does not occur. Furthermore, we found no significant number of resistant A. fumigatus isolates after antifungal drugs were used for therapeutic purposes. Resistance of A. fumigatus against ITZ was documented for the first time in the Netherlands, although the prevalence appears to be very low.

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38th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 38th