Antifungal Activity of Isavuconazole and Comparator Agents against Contemporaneous Mucorales Isolates from USA, Europe, and Asia-Pacific

Isavuconazole is the only US FDA-approved antifungal for treating invasive mucormycosis. We evaluated isavuconazole activity against a global collection of Mucorales isolates. Fifty-two isolates were collected during 2017–2020 from hospitals located in the USA, Europe, and the Asia-Pacific. Isolates...

Full description

Bibliographic Details
Main Authors: Cecilia G. Carvalhaes, Paul R. Rhomberg, Michael D. Huband, Michael A. Pfaller, Mariana Castanheira
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:Journal of Fungi
Subjects:
Online Access:https://www.mdpi.com/2309-608X/9/2/241
_version_ 1797619943354662912
author Cecilia G. Carvalhaes
Paul R. Rhomberg
Michael D. Huband
Michael A. Pfaller
Mariana Castanheira
author_facet Cecilia G. Carvalhaes
Paul R. Rhomberg
Michael D. Huband
Michael A. Pfaller
Mariana Castanheira
author_sort Cecilia G. Carvalhaes
collection DOAJ
description Isavuconazole is the only US FDA-approved antifungal for treating invasive mucormycosis. We evaluated isavuconazole activity against a global collection of Mucorales isolates. Fifty-two isolates were collected during 2017–2020 from hospitals located in the USA, Europe, and the Asia-Pacific. Isolates were identified by MALDI-TOF MS and/or DNA sequencing and susceptibility tested by the broth microdilution method following CLSI guidelines. Isavuconazole (MIC<sub>50/90</sub>, 2/>8 mg/L) inhibited 59.6% and 71.2% of all Mucorales isolates at ≤2 mg/L and ≤4 mg/L, respectively. Among comparators, amphotericin B (MIC<sub>50/90</sub>, 0.5/1 mg/L) displayed the highest activity, followed by posaconazole (MIC<sub>50/90</sub>, 0.5/8 mg/L). Voriconazole (MIC<sub>50/90</sub>, >8/>8 mg/L) and the echinocandins (MIC<sub>50/90</sub>, >4/>4 mg/L) had limited activity against Mucorales isolates. Isavuconazole activity varied by species and this agent inhibited at ≤4 mg/L 85.2%, 72.7%, and 25% of <i>Rhizopus</i> spp. (<i>n</i> = 27; MIC<sub>50/90</sub>, 1/>8 mg/L), <i>Lichtheimia</i> spp. (<i>n</i> = 11; MIC<sub>50/90</sub>, 4/8 mg/L), and <i>Mucor</i> spp. (<i>n</i> = 8; MIC<sub>50</sub>, >8 mg/L) isolates, respectively. Posaconazole MIC<sub>50/90</sub> values against <i>Rhizopus</i>, <i>Lichtheimia</i>, and <i>Mucor</i> species were 0.5/8 mg/L, 0.5/1 mg/L, and 2/- mg/L, respectively; amphotericin B MIC<sub>50/90</sub> values were 1/1 mg/L, 0.5/1 mg/L, and 0.5/- mg/L, respectively. As susceptibility profiles varied among Mucorales genera, species identification and antifungal susceptibility testing are advised whenever possible to manage and monitor mucormycosis.
first_indexed 2024-03-11T08:35:16Z
format Article
id doaj.art-0ce1fa506faf4f1692048a83fe004569
institution Directory Open Access Journal
issn 2309-608X
language English
last_indexed 2024-03-11T08:35:16Z
publishDate 2023-02-01
publisher MDPI AG
record_format Article
series Journal of Fungi
spelling doaj.art-0ce1fa506faf4f1692048a83fe0045692023-11-16T21:31:02ZengMDPI AGJournal of Fungi2309-608X2023-02-019224110.3390/jof9020241Antifungal Activity of Isavuconazole and Comparator Agents against Contemporaneous Mucorales Isolates from USA, Europe, and Asia-PacificCecilia G. Carvalhaes0Paul R. Rhomberg1Michael D. Huband2Michael A. Pfaller3Mariana Castanheira4JMI Laboratories, 345 Beaver Kreek Centre, North Liberty, IA 52317, USAJMI Laboratories, 345 Beaver Kreek Centre, North Liberty, IA 52317, USAJMI Laboratories, 345 Beaver Kreek Centre, North Liberty, IA 52317, USAJMI Laboratories, 345 Beaver Kreek Centre, North Liberty, IA 52317, USAJMI Laboratories, 345 Beaver Kreek Centre, North Liberty, IA 52317, USAIsavuconazole is the only US FDA-approved antifungal for treating invasive mucormycosis. We evaluated isavuconazole activity against a global collection of Mucorales isolates. Fifty-two isolates were collected during 2017–2020 from hospitals located in the USA, Europe, and the Asia-Pacific. Isolates were identified by MALDI-TOF MS and/or DNA sequencing and susceptibility tested by the broth microdilution method following CLSI guidelines. Isavuconazole (MIC<sub>50/90</sub>, 2/>8 mg/L) inhibited 59.6% and 71.2% of all Mucorales isolates at ≤2 mg/L and ≤4 mg/L, respectively. Among comparators, amphotericin B (MIC<sub>50/90</sub>, 0.5/1 mg/L) displayed the highest activity, followed by posaconazole (MIC<sub>50/90</sub>, 0.5/8 mg/L). Voriconazole (MIC<sub>50/90</sub>, >8/>8 mg/L) and the echinocandins (MIC<sub>50/90</sub>, >4/>4 mg/L) had limited activity against Mucorales isolates. Isavuconazole activity varied by species and this agent inhibited at ≤4 mg/L 85.2%, 72.7%, and 25% of <i>Rhizopus</i> spp. (<i>n</i> = 27; MIC<sub>50/90</sub>, 1/>8 mg/L), <i>Lichtheimia</i> spp. (<i>n</i> = 11; MIC<sub>50/90</sub>, 4/8 mg/L), and <i>Mucor</i> spp. (<i>n</i> = 8; MIC<sub>50</sub>, >8 mg/L) isolates, respectively. Posaconazole MIC<sub>50/90</sub> values against <i>Rhizopus</i>, <i>Lichtheimia</i>, and <i>Mucor</i> species were 0.5/8 mg/L, 0.5/1 mg/L, and 2/- mg/L, respectively; amphotericin B MIC<sub>50/90</sub> values were 1/1 mg/L, 0.5/1 mg/L, and 0.5/- mg/L, respectively. As susceptibility profiles varied among Mucorales genera, species identification and antifungal susceptibility testing are advised whenever possible to manage and monitor mucormycosis.https://www.mdpi.com/2309-608X/9/2/241<i>Rhizopus</i><i>Rhizomucor</i><i>Lichtheimia</i>azolesantifungal activitymucormycosis
spellingShingle Cecilia G. Carvalhaes
Paul R. Rhomberg
Michael D. Huband
Michael A. Pfaller
Mariana Castanheira
Antifungal Activity of Isavuconazole and Comparator Agents against Contemporaneous Mucorales Isolates from USA, Europe, and Asia-Pacific
Journal of Fungi
<i>Rhizopus</i>
<i>Rhizomucor</i>
<i>Lichtheimia</i>
azoles
antifungal activity
mucormycosis
title Antifungal Activity of Isavuconazole and Comparator Agents against Contemporaneous Mucorales Isolates from USA, Europe, and Asia-Pacific
title_full Antifungal Activity of Isavuconazole and Comparator Agents against Contemporaneous Mucorales Isolates from USA, Europe, and Asia-Pacific
title_fullStr Antifungal Activity of Isavuconazole and Comparator Agents against Contemporaneous Mucorales Isolates from USA, Europe, and Asia-Pacific
title_full_unstemmed Antifungal Activity of Isavuconazole and Comparator Agents against Contemporaneous Mucorales Isolates from USA, Europe, and Asia-Pacific
title_short Antifungal Activity of Isavuconazole and Comparator Agents against Contemporaneous Mucorales Isolates from USA, Europe, and Asia-Pacific
title_sort antifungal activity of isavuconazole and comparator agents against contemporaneous mucorales isolates from usa europe and asia pacific
topic <i>Rhizopus</i>
<i>Rhizomucor</i>
<i>Lichtheimia</i>
azoles
antifungal activity
mucormycosis
url https://www.mdpi.com/2309-608X/9/2/241
work_keys_str_mv AT ceciliagcarvalhaes antifungalactivityofisavuconazoleandcomparatoragentsagainstcontemporaneousmucoralesisolatesfromusaeuropeandasiapacific
AT paulrrhomberg antifungalactivityofisavuconazoleandcomparatoragentsagainstcontemporaneousmucoralesisolatesfromusaeuropeandasiapacific
AT michaeldhuband antifungalactivityofisavuconazoleandcomparatoragentsagainstcontemporaneousmucoralesisolatesfromusaeuropeandasiapacific
AT michaelapfaller antifungalactivityofisavuconazoleandcomparatoragentsagainstcontemporaneousmucoralesisolatesfromusaeuropeandasiapacific
AT marianacastanheira antifungalactivityofisavuconazoleandcomparatoragentsagainstcontemporaneousmucoralesisolatesfromusaeuropeandasiapacific