Intra- and Interlaboratory Study of Antifungal Susceptibility Testing of Isavuconazole against Aspergillus Strains

Ref ID: 19260

Author:

M. A. Ghannoum, V. Chaturvedi, A. Espinel-Ingroff, A. Fothergill, R. Jones, L. Ostrosky-Zeichner, R. Rennie, T. Walsh

Author address:

Case Western Reserve Univ. Sch. of Med, Cleveland, OH, USA.

Full conference title:

53rd Interscience Conference on Antimicrobial Agents and Chemotherapy

Date: 10 September 2014

Abstract:

Background. Isavuconazole (ISA) is a novel broad-spectrum triazole, which is in clinical phase III development for the treatment of severe invasive fungal infections, including aspergillosis. The CLSI broth microdilution method for filamentous fungi (M38-A2)does not specifically reference ISA. Standard inter- and intra-laboratory studies were conducted to: 1) evaluate the reproducibility of minimum inhibitory concentrations (MICs) of ISA against recent clinical isolates of Aspergillus spp, and 2) to select QC strains for inclusion in the M38-A2 document . Methods. Eight laboratories tested 15 clinical strains of Aspergillus spp. (A. fumigatus, A. flavus, A. terreus, and A. niger) in 3 lots of RPMI-1640 using frozen panels prepared by ThermoFisher (Cleveland, OH). Ten replicates of each strain were tested, with results recorded at 50% and 100% inhibition at 48
hrs. The % of MICs falling within a four doublingdilution
range was expressed as the % agreement,
with >90% agreement considered to be acceptable.
Results. All 15 Aspergillus strains showed excellent
agreement of >94% at the 100% inhibition endpoint
for ISA. Furthermore, ISA MICs against 13 of 15
strains showed acceptable agreement at the 50%
inhibition endpoint. Conclusions. Based on this
study, it is recommended to read ISA MICs
against Aspergillus strains at the 100% inhibition
endpoint, which is the standard for azoles against
filamentous fungi. Furthermore, two QC strains were
selected for testing ISA againstAspergillus isolates:
1) Paecilomyces variotii MYA 3630, approved range –
0.06-0.5 μg/ml and 2)Aspergillus flavus ATCC
204304, approved range – 0.5-4 μg/ml. These also
serve as QC strains for most antifungals already
included in the M38-A2 standard. Overall, ISA
demonstrated excellent reproducibility of MIC data
when tested against Aspergillus isolates.

Abstract Number: NULL

Conference Year: 2013

Link to conference website: NULL

New link: NULL

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