In Vitro Activity of Micafungin Compared with Five other Antifungal Agents against 273 Prospectively Collected Clinical Aspergillus Isolates from The Netherlands

Ref ID: 18651

Author:

I. Curfs, BSc – Senior technician 1, P. J. Haas, MD. PhD – Consultant 2, M. Wolfhagen, MD, PhD – Consultant 3, K. Verduin, MD, PhD – Consultant 4, C. Bens, BSc – Technician Molecular Biology 1, C. H. Klaassen, PhD – Molecular biologist 1, J. F. Meis,

Author address:

1Canisius-Wilhelmina Hosp., Nijmegen, Netherlands, 2Univ. Med. Ctr. Utrecht, Utrecht, Netherlands, 3Isala Hosp., Zwolle, Netherlands, 4PAMM, Veldhoven, Netherlands, 5Radboud Univ. Nijmegen Med. Ctr., Nijmegen, Netherlands.

Full conference title:

52nd Annual ICAAC

Date: 9 September 2014

Abstract:

Background: Voriconazole is the first line treatment of invasive aspergillosis. A multicentre surveillance of azole resistance in the Netherlands in 2005 reported a 2% triazole resistance rate, but no resistance for echinocandins was found. The latter study was repeated in 2010 to record any changes in prevalence of triazole or echinocandin resistance. Methods: MICs of 273 Aspergillus isolates, prospectively collected from five (non)academic centers in the Netherlands during a 6-month period in 2010, were determined for amphotericin B, itraconazole, voriconazole, posaconazole, caspofungin and micafungin (CLSI M38-A2). Azole resistance was confirmed by molecular analysis of the underlying mutation(s) in the cyp51A gene. Results: Species distribution was 86% A. fumigatus and 14% non-fumigatus Aspergillus species. Among A. fumigatus (n= 235), MIC90 and MIC range (mg/L) of amphotericin B, itraconazole, voriconazole, posaconazole, caspofungin and micafungin were 0.5, 0.125-1; 0.5, 0.063->16; 2, 0.125->16; 0.25, <0.016-2; 0.5, 0.016-1; 0.016, <0.008-0.125 respectively. A. fumigatus isolates with MICs outside the wildtype cutoff values of itraconazole (>2 mg/L), voriconazole (>2 mg/L) or posaconazole (>0.5 mg/L) occurred in 7%, 7% and 5% of isolates. The MIC90 and MIC range of micafungin for these azole resistant A. fumigatus strains was 0.031 mg/L and <0.008-0.063 mg/L. Fourteen A. fumigatus strains with itraconazole MIC ≥ 16 mg/L and voriconazole MIC ≥ 4 mg/L had the TR34L98H mutation in the cyp51A gene (6%). One isolate had a G54W mutation. Conclusions: Azole resistance in clinical A. fumigatus increased from 2% in 2005 to 6% in 2010 in the Netherlands. Echinocandins have still low MICs, also for azole resistant isolates. Sponsored by Astellas Pharma, the Netherlands.

Abstract Number: M-334

Conference Year: 2012

Link to conference website: NULL

New link: NULL

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