OVERALL MANAGEMENT OF ASPERGILLOSIS AND MUCORMYCOSIS

George R Thompson, III, MD: Let’s put this data in context. When we consider the current Infectious Diseases Society of America (IDSA) guidelines for aspergillosis, azoles are the preferred agents for treatment of invasive aspergillosis in many settings.34 But we’re in a time where we have three different mold-active triazoles available, and probably the next IDSA guidelines will consider those fairly equivalent for the treatment of invasive aspergillosis.

What about management of mucormycosis? In adults, I think a lot of people have adopted the following approach: start up front with lipid amphotericin B, although isavuconazole is a first-line option, at least in adult patients in some settings, and then use isavuconazole as part of step-down therapy.

Antonio Arrieta, MD: We also typically start with liposomal amphotericin B in many cases. We use isavuconazole when there is toxicity or failure with amphotericin B or as step-down therapy because we are succeeding and willing to send the patient home on oral therapy. Let me go through the rationale. The data for Mucor are less solid. Many of our recommendations are based on the significant decrease in the fungal burden in animals who were treated with amphotericin B and echinocandins. So, at least when I have to face one of these patients with such a high mortality, I think that I can add an echinocandin to amphotericin B. When it comes to data from clinical studies, the data from the VITAL study suggest that isavuconazole had similar success rates as amphotericin B products. These were patients who were identified from Fungiscope database, and they compared their outcomes to those who were being treated in the isavuconazole study. The data suggest, at least in the worst-case scenario, that isavuconazole and amphotericin B are fairly comparable, with the added safety of isavuconazole.35

So, one would think, based on the data, that isavuconazole ought to be the agent to be started when one is suspecting mucormycosis. But I don’t think that the people who are making recommendations are ready yet to jump into the triazole environment. Most experts, at least in pediatrics, recommend for the management of Mucor starting with liposomal amphotericin B at very high doses up to 10 mg/kg.26 There is very little value in increasing the dosage to 12 mg/kg with a substantial increase in toxicity. Isavuconazole though, plays an important role in the treatment of Mucor, particularly when safety, efficacy, and quality of life need to be considered. For example, it’s important  to keep in mind that we do not send patients home while receiving amphotericin B products. You would then have patients who had to stay in the hospital for weeks or months. But when the patient is showing improvement, or if the patient is not tolerating amphotericin B products, then we switch to isavuconazole IV or oral. Some early studies showed that isavuconazole was an agent that could be used for rescue.36 These data along with the data comparing isavuconazole with amphotericin B suggest that the efficacy should be comparable.

George R Thompson, III, MD: That’s interesting that the pediatric patients tolerate such high doses of amphotericin B. We’ve certainly tried that in adults, but there was renal toxicity.37 I think you have the advantage that kids have healthier kidneys in general, but I think that’s great that you’re able to do that and really give them a higher dose and attempt to improve efficacy.

Antonio Arrieta, MD: Then I always wonder if these patients are going to be hypertensive when they’re older or if they’re going to have pre-eclampsia when they’re pregnant. We typically use creatinine, which is a crude marker of renal toxicity, for safety monitoring and often their creatinine holds, but we don’t really know what we’re doing to the kidneys. I always wonder if these patients are going to have problems later.

TABLE OF CONTENTS

Faculty

George R. Thompson, III, MD

Professor of Medicine
University of California, Davis, School of Medicine
Sacramento, California

Antonio C. Arrieta, MD

Division Chief
Pediatric Infectious Diseases
Children’s Hospital of Orange County (CHOC)
Orange, California

MyCARE thanks Astellas for sponsoring this activity.

Copyright © 2025. ALL RIGHTS RESERVED. MyCARE Foundation. Astellas-sponsored, MA-MM-14973. May 2025. ASTELLAS and the Flying Star Logo are registered trademarks of Astellas Pharma Inc. Used with permission.