Evaluation of isavuconazole (BAL8557/BAL4815) Etest compared to broth microdilution antifungal susceptibility testing against quality control strains and fluconazole-susceptible clinical Candida isolates

Abstract number: 1733_1172

Heep M., Grover P., Brown N.P., Sahm D., Jones M.E.

Background: Isavuconazole (ISA, BAL8557/BAL4815) is a new broad-spectrum triazole. In preparation of clinical trials in primary and salvage treatment of invasive fungal infections, options allowing susceptibility testing were evaluated. Agar-based methods such as Etest may be preferred by some clinical laboratories for their simplicity and ease of use. Broth microdilution (BMD) is a reference method for antifungal susceptiblity testing (AFST) against which the Etest method was validated.

Methods: Etest was performed according to manufacturer's instructions (AB Biodisk) and BMD according to CLSI M27-A2 guideline. Organisms tested were C. parapsilosis ATCC 22019, C. krusei ATCC 6258 and 4 clinical isolates of C. parapsilosis, C. glabrata, C. tropicalis, C. krusei. On three separate days a total of 14 individual inoculum suspensions for each test organism was prepared and used concomitantly for Etest and broth microdilution; voriconazole and fluconazole were included as reference. Both Etest and BMD results were read at 24 and 48 hours incubation. Concordance between methods was defined as within 1 doubling dilution of the BMD MIC.

Results: For ISA 100% concordance was detected between BMD and Etest at 24 h for C. parapsilosis ATCC 22019 (BMD MIC range 0.015 ug/mL; Etest MIC range 0.012–0.016 mg/L) and C. krusei ATCC 6258 (BMD MIC range 0.06–0.12 mg/L; Etest MIC range 0.0125 mg/L); and at 48 h for C. parapsilosis ATCC 22019 (BMD MIC range 0.03 mg/L; Etest MIC range 0.016–0.023 mg/L) and C. krusei ATCC 6258 (BMD MIC range 0.25 mg/L; Etest MIC range 0.0125–0.19 mg/L).

Similarly for all clinical isolates 100% of results were concordant at both 24 h and 48 h with the exception of one 24 h inoculum suspension (BMD 0.06 mg/L versus Etest 0.25 mg/L), one 48 h inoculum suspension (BMD 2 mg/L versus Etest 0.75 mg/L) of C. glabrata 1547507; and two inoculum suspensions (both BMD 1 mg/L versus 0.38 mg/L Etest) of C. krusei 1547509.

Conclusions: For the ATCC quality control strains and susceptible clinical isolates ISA Etest results correlated well with the CLSI M27-A2 BMD method. This agar-based method represents a simple and reliable method for determining ISA susceptibility of Candida spp. Additional testing will establish concordance between methods for ISA-resistant isolates.

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Location: ICC, Munich, Germany
Presentation type:
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