Purpose: Invasive aspergillosis is an important cause of mortality and morbidity especially in immunocompromised individuals. A. fumigatus is the most common agent causing those infections followed by A. flavus. Although the in-vitro activity of antifungals against isolates of A. fumigatus is well understood, few data exist to define the activity of drugs against strains of A. flavus. Isavuconazole, an experimental broad spectrum antifungal triazole agent, has shown good antifungal activity against clinical isolates of yeasts (including fluconazole-resistant strains) and moulds (including itraconazole or amphotericin resistant strains). Antifungal activity of this agent has been tested with only few isolates of A. flavus. This study was carried out to determine in-vitro activity of isavuconazole and to compare its activity against other antifungal agents against a large collection of isolates of A .flavus. Here we determined the in vitro activity of eight existing and new antifungal drugs against A. flavus. Methods: A collection of 188 isolates of A. flavus (178-clinical; 10-environmental) obtained from the National Culture Collection of Pathogenic Fungi (NCCPF), Chandigarh India, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands and Fungal Biodiversity Centre, Utrecht, The Netherlands. The identities of the isolates were confirmed by Amplified Fragment Length Polymorphism. MICs were determined for isavuconazole (ISA), Itraconazole ( ITC), voriconazole (VOR), posaconazole (POS) and amphotericin B (AmB) or MECs for caspofungin (CAS) anidulafungin (ANI) and micafungin (MICA). Microdilution testing was done in accordance with CLSI M38-A2 guidelines. Quality control was ensured by including Paecilomyces variotii (ATCC 22319) and Candida krusei (ATCC 6258). Results: MIC ranges and MIC50 and MIC90 values (mg/L) of all A. flavus isolates are shown in table below: Conclusions: Isavuconazole showed good activity against A. flavus isolates ( MIC 90 1mg/L). MIC90 for VOR, POS, ITR were 2, 0.25, 0.25mg/L respectively. Though AmB resistance was seen only with three isolates, the MIC values for the rest were relatively in higher range (MIC 50 - 0.5mg/L and MIC 90 1mg/L). All echinocandins showed good activity against all the isolates of A. flavus. Acknowledgement: This study was supported by an educational grant from Basilea Pharmaceuticals International, Basel, Switzerland.
Full conference title:
4th Advances Against Aspergillosis
- AAA 4th (2010)