Evaluation of the in vitro activity of isavuconazole and comparator voriconazole against 2635 contemporary clinical Candida and Aspergillus isolates

K M T Astvad, R K Hare, M C Arendrup

35 Citations (Scopus)

Abstract

OBJECTIVE: The in vitro activity of isavuconazole was determined for 1677 Candida and 958 Aspergillus isolates from 2012 to 2014 with voriconazole as comparator.

METHODS: Aspergillus isolates were screened for resistance using azole-agar. Aspergillus isolates that screened positive and all Candida isolates underwent EUCAST broth microdilution testing. Isolates were categorized as wild-type (wt) or non-wt, adopting EUCAST epidemiological cut-off values (ECOFFs) (where available) or wt upper limits (wtULs; two two-fold dilutions above the MIC50). The CYP51A gene was sequenced for non-wt Aspergillus fumigatus isolates. Itraconazole and posaconazole MICs were determined for selected Aspergillus isolates with isavuconazole MIC ≥2 mg/L.

RESULTS: Isavuconazole MIC50(range) (mg/L) against Candida species were: Candida albicans: ≤0.03 (≤0.03 to >4), Candida dubliniensis: ≤0.03 (≤0.03), Candida glabrata: ≤0.03 (≤0.03-4), Candida krusei: 0.06 (≤0.03-0.5), Candida parapsilosis: ≤0.03 (≤0.03-0.06), Candida tropicalis: ≤0.03 (≤0.03 to >4), Saccharomyces cerevisiae (anamorph: Candida robusta): ≤0.03 (≤0.03-0.5). Non-wt isavuconazole/voriconazole MICs were found for C. albicans: 0.8/1.0%, C. dubliniensis: 0/1.8%, C. glabrata: 14.9/9.5%, C. krusei: 2.7/1.4%, C. parapsilosis: 1.7/1.8%, C. tropicalis: 14.3/19.1% and S. cerevisiae: 10.0/0%. Isavuconazole MIC50(range) (mg/L) against Aspergillus species were: A. fumigatus: 1 (≤0.125 to >16), Aspergillus niger: 2 (1-8), Aspergillus terreus: 1 (0.25-8), Aspergillus flavus: 1 (0.5-2), Aspergillus nidulans: ≤0.125 (≤0.125-0.25). Non-wt isavuconazole/voriconazole MICs were found for 13.7/15.2% A. fumigatus, 4.9/0% A. niger and 48.2/22.2% A. terreus.

CONCLUSION: Isavuconazole displayed broad in vitro activity, similar to that of voriconazole. Up to 15% of C. glabrata, C. tropicalis and A. fumigatus isolates were non-wt, reflecting increased resistance at a reference centre and technical issues. Significant CYP51A alterations were reliably detected applying the isavuconazole breakpoint.

Original languageEnglish
JournalClinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
Volume23
Issue number11
Pages (from-to)882-887
Number of pages6
ISSN1198-743X
DOIs
Publication statusPublished - Nov 2017

Keywords

  • Journal Article

Fingerprint

Dive into the research topics of 'Evaluation of the in vitro activity of isavuconazole and comparator voriconazole against 2635 contemporary clinical Candida and Aspergillus isolates'. Together they form a unique fingerprint.

Cite this