In Vitro Activity of Isavuconazole compared with Itraconazole, Voriconazole, and Posaconazole in azole-resistant Aspergillus fumigatus

Ref ID: 19280

Author:

S. Seyedmousavi, A. J. Rijs, W. J. Melchers, J. W. Mouton, P. E. Verweij

Author address:

Radboud Univ. Nijmegen Med. Ctr., Nijmegen, NETHERLANDS; Nijmegen Inst. Infect. Inflamm. Immun, Nijmegen, NETHERLANDS.

Full conference title:

53rd Interscience Conference on Antimicrobial Agents and Chemotherapy

Date: 10 September 2014

Abstract:

Background: The drugs recommended for treatment of Aspergillus fumigatus diseases are the mold-active azole antifungal drugs. However, a wide range of mutations in A. fumigatus confer resistance to itraconazole (ITC), voriconazole (VRC) and posaconazole (POS), which commonly involves modifications in the cyp51A gene. We investigated the in vitro efficacy of a new triazole isavuconazole (ISA) againstA.fumigatus isolates harboring various cyp51A mutations. Methods: The comparative in vitro activity of ITC, VRC, POS and ISA was determined against 5 wild-type (WT) and 16 azole-resistant clinicalA.fumigatus isolates (mutations: G54W, TR34/L98H and TR46/Y121/T289) using EUCAST checkerboard microdilution method with spectrophotometric analysis, followed by a viability-based XTT assay within 2 h of exposure after 24 and 48 h of incubation at 35°C to 37°C. All experiments were performed in three independent replicates. Results: The geometric MIC90 means were: WT isolates: ITC, 0.175 mg/L, VRC, 0.45 mg/L, POS, 0.031 mg/L and ISA, 1 mg/L; G54W isolates (n=2): ITC, > 16 mg/L, VRC, 0.375 mg/L, POS, >16 mg/L and ISA, 0.5 mg/L; TR34/L98H isolates (n=10); ITC, > 16 mg/L, VRC, 6 mg/L, POS, 0.77 mg/L and ISA, 14.22 mg/L; TR46/Y121F/T289A isolates (n=4); ITC, 5.75 mg/L, VRC,
>16 mg/L, POS, 0.93 mg/L and ISA, >16
mg/L. Conclusions: Our results indicated that ISA had low
MICs (8804; 1 mg/L) against WT A.fumigatus. Variable ISA
activity was found in azole resistant isolates: ISA showed
cross-resistance to VRC, but not with ITC and POS. In
vivo studies are required to validate the potential efficacy
of ISA against azole-resistant invasive aspergillosis.

Abstract Number: NULL

Conference Year: 2013

Link to conference website: NULL

New link: NULL

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