A global perspective of the changing epidemiology of invasive fungal disease and real-world experience with the use of isavuconazole

Abstract

Global epidemiological data show that the incidence of invasive fungal disease (IFD) has increased in recent decades, with the rising frequency of infections caused by Aspergillus and Mucorales order species. The number and variety of patients at risk of IFD has also expanded, owing in part to advances in the treatment of hematologic malignancies and other serious diseases, including hematopoietic stem cell transplantation (HCT) and other therapies causing immune suppression. Isavuconazonium sulfate (active moiety: isavuconazole) is an advanced-generation triazole antifungal approved for the treatment of invasive aspergillosis and mucormycosis that has demonstrated activity against a variety of yeasts, moulds, and dimorphic fungi. While real-world clinical experience with isavuconazole is sparse in some geographic regions, it has been shown to be effective and well tolerated in diverse patient populations, including those with multiple comorbidities who may have failed to respond to prior triazole antifungal therapy. Isavuconazole may be suitable for patients with IFD receiving concurrent QTc-prolonging therapy, as well as those on venetoclax or ruxolitinib. Data from clinical trials are not available to support the use of isavuconazole prophylactically for the prevention of IFD or for the treatment of endemic IFD, such as those caused by Histoplasma spp., but real-world evidence from case studies suggests that it has clinical utility in these settings. Isavuconazole is an option for patients at risk of IFD, particularly when the use of alternative antifungal therapies is not possible because of toxicities, pharmacokinetics, or drug interactions.

Keywords: Fungal epidemiology; antifungal therapy; healthcare resource utilization; invasive fungal disease; isavuconazonium sulfate; real-world.

Figure 1.

Regional mortality rates^a attributed to invasive fungal disease at 3 months (unless otherwise specified).^,,,,, aThe definition of mortality varied across the studies; please refer to Table 1 for details. IA, invasive aspergillosis; IC, invasive candidiasis; IFD, invasive fungal infections; IMD, invasive mould disease; IMI, invasive mould infection.

Figure 2.

Incidence or prevalence of invasive fungal disease across different geographies over time.^, aStudy covered various periods, with results extrapolated to the total population of the respective country in the year shown in the figure; ^bCountries included: China, India, Singapore, Taiwan, and Thailand; ^cCountries included: Egypt, Lebanon, Saudi Arabia, Iran, Iraq, and Algeria; ^dRange of studies included. alloHCT, allogeneic hematopoietic stem cell transplantation; AML, acute myeloid leukemia; CNPA, chronic necrotizing pulmonary aspergillosis; CPA, chronic pulmonary aspergillosis; HCT, hematopoietic stem cell transplantation; IA, invasive aspergillosis; IC, invasive candidiasis; ICU, intensive care unit; IFD, invasive fungal disease; IMD, invasive mould disease; IMI, invasive mould infection; IPA, invasive pulmonary aspergillosis.