Background: Invasive aspergillosis remains an important cause of morbidity and mortality. Isavuconazole (ISA) is a novel, intravenous and orally available, broad-spectrum, water-soluble triazole currently in Phase III clinical trials for treatment of patients with invasive Aspergillus, Candida, and rare mould infections, including patients with renal impairment. The active moiety of ISA is BAL4815, which has been shown to have in vitro antifungal activity against clinically relevant species of yeasts and moulds including Aspergillus as well as Zygomycetes.
Methods and Results: We examined the in vitro activity of ISA against 1488 isolates of Aspergillus (Table 1). These data represent a compilation of minimal inhibitory concentration (MIC) data from 7 published reports and 2 unpublished laboratory studies undertaken by various academic investigators in EU and US laboratories during the period 2004-2010. All MIC data in the pooled analysis were derived using CLSI (M38-A) or EUCAST standard methodologies, although there were differences in methodologies between the test centers related to incubation period, determination of MIC endpoint, and number of replicates.
Results: Overall, ISA was active against all clinically relevant species of Aspergillus tested. The MIC results were evaluated at either 24 hours or 48 hours. The ISA and voriconazole (VRC) MIC ranges, MIC50s, and MIC90s are listed in Table 1 for each of the Aspergillus species tested. For the majority of the Aspergillus species, the 24 hour and 48 hour MIC results were within a 2-fold dilution for both ISA and VRC. At 24 and 48 hours, the overall MIC90 for all Aspergillus species was 1.0 mg/L for both ISA and VRC.
Conclusions: This pooled analysis of multiple studies demonstrates the potent in vitro activity of ISA against diverse range of Aspergillus species, including species refractive to other therapies such as A. terreus. These MICs are within clinically relevant concentrations achievable with clinical dosing. ISA is a promising agent for the treatment of invasive aspergillosis.
- ECCMID 22nd (2012)