In-vitro activity of isavuconazole against candida isolates from the EU and USA with reduced susceptibility to fluconazole: a pooled analysis from eight studies

Ref ID: 19176

Author:

J.I. Smart, M.E. Jones, L.L. Kovanda

Author address:

Northbrook, US; Basel, CH

Full conference title:

23rd European Congress of Clinical Microbiology and
Infectious Diseases

Date: 27 April 2014

Abstract:

Objectives: Isavuconazonium sulphate is a novel, broad-spectrum, water-soluble, triazole agent with intravenous (IV) and oral formulations currently in global Phase 3 clinical trials for treatment of invasive infections caused by Aspergillus spp., Candida spp., and rare fungal infections, including infections in patients with renal impairment. Its active moiety, isavuconazole (ISA; BAL4815), has been shown to have in-vitro antifungal activity against clinically relevant species of yeasts and moulds, including Candida spp. with reduced susceptibility to currently used azoles.
Methods: We examined the in-vitro activity of ISA against clinically relevant Candida spp. with reduced susceptibility to fluconazole (FLU) as defined by the current CLSI-approved susceptible dose-dependent breakpoints (C. albicans MIC >=4 mg/L and C. glabrata MIC >=32 mg/L). These data represent a compilation of Minimal Inhibitory Concentration (MIC) data for ISA and voriconazole (VRC) from 8 individual studies undertaken by academic investigators in EU and USA laboratories during the period 2004-2010. All MIC data in the pooled analysis were derived using CLSI (M38-A) methodology, with MIC evaluation at 24 and 48 h.
Results: ISA exhibited good activity against isolates of Candida spp. with reduced susceptibility to FLU. ISA MIC50s for both C. albicans and C. glabrata were 2-4 fold lower than MIC50s for VRC at both 24 and 48 h with the exception of C. albicans 48 h MIC50, which was 0.25 mg/L for ISA and 0.125 mg/L for VRC (Table).
Conclusions: This pooled analysis of multiple studies demonstrates the potent in-vitro activity of ISA against Candida spp. with reduced susceptibility to FLU. Furthermore, the ISA MIC50s were below the anticipated trough levels reached with the dosing regimen being tested in the ongoing Phase 3 studies. Therefore, these data suggest that ISA has the potential for broader coverage than VRC against Candida spp. with reduced susceptibility to FLU, in particular C. glabrata.

Abstract Number: P983

Conference Year: 2013

Link to conference website: http://registration.akm.ch/einsicht.php?XNABSTRACT_ID=163422&XNSPRACHE_ID=2&XNKONGRESS_ID=180&XNMASK

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