P-1193. Activity of isavuconazole against contemporary Mucorales from a worldwide surveillance program

TL;DR

This study evaluates isavuconazole's effectiveness against Mucorales fungi causing invasive mucormycosis, showing it works well against some species but less so against Mucor.

Contribution

The study provides the first global assessment of isavuconazole's activity against contemporary Mucorales isolates from invasive fungal infections.

Findings

Isavuconazole had lower MICs than voriconazole and comparable MICs to posaconazole against Lichtheimia, Rhizomucor, and Rhizopus spp.

Higher MICs were observed for isavuconazole and posaconazole against Mucor spp.

Amphotericin B showed MICs ≤ 2 mg/L across all Mucorales genera.

Abstract

Isavuconazole (ISA) is the only US FDA-approved antifungal agent with labeling for the treatment of invasive mucormycosis (IM). The prevalence of IM has risen due to the increased use of immunosuppressive agents and conditions which increase the risk of IM. Liposomal amphotericin B (AMB) is typically first-line empirical treatment for IM but has increased toxicity compared to ISA and is only available in an intravenous (IV) formulation while ISA is available in both oral and IV delivery.Mucorales species represented in surveillance testingInfection source for collected Mucorales isolates

Mucorales species represented in surveillance testing

Infection source for collected Mucorales isolates

A total of 66 Mucorales isolates from invasive fungal infections collected at 27 hospitals in 13 countries between 2021 - 2024 were tested. Confirmatory identification was performed by MALDI or 28S and ITS sequencing. Isolates were tested by reference broth microdilution method according to CLSI guidelines against voriconazole (VRC), posaconazole (POS), ISA, and AMB. No CLSI breakpoints or epidemiological cutoff values are available for interpretation of MICs.MIC range (mg/L), MIC50/90 (mg/L), for isavuconazole and comparator agents for all tested MucoralesISA, isavuconazole; VRC, voriconazole; POS, posaconazole; AMB, amphotericin B*MIC50 only as < 10 organisms representedaNo range as all organisms at same MIC

MIC range (mg/L), MIC50/90 (mg/L), for isavuconazole and comparator agents for all tested Mucorales

ISA, isavuconazole; VRC, voriconazole; POS, posaconazole; AMB, amphotericin B

*MIC50 only as < 10 organisms represented

aNo range as all organisms at same MIC

11 different organism groups were represented (Figure 1). Infection source was varied (Figure 2). Across all Mucorales, ISA MICs ranged from 0.12 - > 8 mg/L with MIC50 2 mg/L, which was lower than that of VRC and comparable to POS (within 2 doubling dilutions, Table 1). When analyzing individual genera, lower MICs were observed for ISA and POS against Lichtheimia (100% ≤ 4mg/L), Rhizomucor (100% ≤ 4mg/L), and Rhizopus spp. (89.2% and 91.9% ≤ 4mg/L, respectively). However, higher MICs were observed for ISA and POS against Mucor spp. (23.5% ≤ 4mg/L). AMB MICs were ≤ 2 mg/L across all genera.

ISA and POS have low MICs against Lichtheimia, Rhizomucor, and Rhizopus spp. isolates collected from IM infections worldwide between 2021 and 2024. Higher MICs are observed for Mucor spp. Given its FDA indication, delivery mechanisms, side-effect profile and drug-drug interactions, ISA is often preferred for long-term treatment of IM compared to AMB or POS. These data support the use of ISA for treatment of IM if Lichtheimia, Rhizomucor, or Rhizopus spp. are identified as the causative organism but waiting for MIC results if Mucor spp. is identified.

Marisa Winkler, MD, PhD, Basilea: Advisor/Consultant|Basilea: Grant/Research Support|GSK: Advisor/Consultant|GSK: Grant/Research Support|Melinta Therapeutics: Advisor/Consultant|Melinta Therapeutics: Grant/Research Support|Mundipharma: Advisor/Consultant|Mundipharma: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pulmocide: Advisor/Consultant|Pulmocide: Grant/Research Support Mariana Castanheira, PhD, Melinta Therapeutics: Advisor/Consultant|Melinta Therapeutics: Grant/Research Support

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