Background: Isavuconazole is a newly licensed compound in Europe. Here we report the in vitro
activity of isavuconazole in comparison with voriconazole against for clinical isolates of Candida and
Aspergillus isolates received in 2012-14 at the national reference laboratory for mycology in Denmark.
Material/methods: 1677 Candida and Saccharomyces isolates and 716 Aspergillus isolates were
received. Species identification was done using morphology supplemented by MALDI-TOF mass
spectrometry for the yeasts and thermotolerance and beta-tubulin sequencing for Aspergillus.
EUCAST susceptibility testing was done following E-Def 7.2 for yeast. For Aspergillus screening for
azole resistance was gradually implemented. Thus MIC determination was performed for 263/716
Aspergillus isolates following E-Def 9.2. Isolates were categorised as wild-type or non-wild-type
isolates adopting EUCAST ECOFFs. For species without ECOFFs, a wild-type upper limit was
determined as two 2-fold dilutions above the modal MIC was used. Thus isavuconazole/voriconazole
ECOFF/ upper limit (mg/L) were: A. flavus: 2/2; A. fumigatus: 2/ 1; A. nidulans: 0.25/1; A. niger: 4/2; A.
terreus 1/2, C. albicans: 0.03/0.125; C. dubliniensis: 0.03/0.125; C. glabrata: 0.125/1; C. krusei
0.125/1; C. parapsilosis: 0.03/0.125; C. tropicalis 0.03/0.125; S. cerevisiae: 0.125/0.25.
Results: Modal MIC (range) (mg/L) for isavuconazole against Candida species were as follows: C.
albicans: ≤0.03 (≤0.03->4), C. dubliniensis: ≤0.03 (≤0.03), C. glabrata: ≤0.03 (≤0.03-4), C. krusei:
≤0.03 (≤0.03-0.5), C. parapsilosis: ≤0.03 (≤0.03–0.06), C. tropicalis: ≤0.03 (≤0.03->4), S. cerevisiae:
≤0.03 (≤0.03 -0.5) and other Candida ≤0.03 (≤0.03->4). Isavuconazole MICs above the wild-type
upper limit were found for 0.84% of C. albicans, 14.89% of C. glabrata, 14.86% of C. krusei, 1.69% of
C. parapsilosis, 14.29% of C. tropicalis and 10.00% of S. cerevisiae. In comparison, voriconazole MIC
values above the ECOFFs were: 0.97% for C. albicans, 1.79% for C. dubliniensis, 9.45% for C.
glabrata, 1.37% for C. krusei, 1.79% for C. parapsilosis, 19.12% for C. tropicalis and 5.00% for S.
cerevisiae. Modal MIC (range) (mg/L) for isavuconazole against Aspergillus species were as follows:
A. calidoustus: n.a. (4), A. flavus: 1 (0.5-2), A. fumigatus: 1 (≤0.125->4), A. nidulans: ≤0.125 (≤0.125-
0.25), A. niger: 2 (1->4), A. tamarii: n.a (0.25), A. terreus: 1 (0.25->4), A. tubingensis n.a. (4 >4).
Isavuconazole MICs above the ECOFFs were found for 0% A. flavus, 14.12% A. fumigatus, 0% A.
nidulans, 5.26% A. niger and 48.15% A. terreus. The similar percentages for voriconazole were: 0% A.
flavus, 15.29% A. fumigatus, 0% A. nidulans, 0% A. niger and 22.22% A. terreus.
Conclusions: overall isavuconazole displayed a broad in vitro activity which was similar to that of
voriconazole. Non wild-type isolates were found in up to 14% C. glabrata, C. krusei, C. tropicalis and
A. fumigatus, but in part reflects the selected isolate population received at a reference laboratory.
Full conference title:
- ECCMID 26th (2016)