Global consumption trend of antifungal agents in humans from 2008 to 2018: data from 65 middle- and high-income countries

Publication summary

Despite the fact that fungal infections cause about 1.7 million deaths globally every year, national infectious diseases surveillance programs often do not collect information on fungal disease or antifungal use, and the World Health Organization (WHO) does not currently have a global fungal infection surveillance program. Appropriate antifungal treatment has the potential to avert almost 80% of fungal disease deaths, yet a lack of access to affordable antifungals hampers rapid and available first-line treatment in many lower-income countries. In this study, researchers analyzed sales of systemic antifungals from 27 middle-income countries and 38 high-income countries from 2008 to 2018 stored by the IQVIA-Multinational Integrated Data Analysis System (MIDAS).

Who this is for

• Managers of global, national, and healthcare-level antimicrobial surveillance systems
• Researchers studying fungal diseases, neglected tropical diseases, and antifungal use

Key findings

• Antifungal use across the 65 countries increased across the study period, from 0.5 Defined Daily Dose/1,000 people/day (DDD) in 2008 to 0.92 DDD in 2018, with a compound annual growth rate of 6.2%. Antifungal use has declined recently in high-income countries, while consumption in middle-income countries—and especially in lower-middle-income countries—continues to rise. Triazole use has increased rapidly in middle-income countries since 2014, and imidazole use declined across high- and middle-income countries.
• In 2018, countries with the highest antifungal sales were Belgium (3.37 DDD), Portugal, Finland, South Korea, and France. Countries with the lowest antifungal use were the Philippines (0.03 DDD), Bosnia and Herzegovina, Jordan, China, and Venezuela.
• The most common antifungals sold in 2018 were itraconazole (0.32 DDD), terbinafine (0.30 DDD), and fluconazole (0.23 DDD). Antifungals with the lowest number of sales included polyenes and echinocandins, possibly due to the fact that they are only available parenterally. Use of polyenes and echinocandins was 10 times higher in high-income countries compared with middle-income countries.
• Itraconazole use soared in middle-income countries after the antifungal was added to the WHO Essential Medicines List in 2017. Increasing itraconazole consumption may also be due to its activity against Aspergillus species and its use as a solution for rising fluconazole resistance in invasive candidemia. Itraconazole access is plagued by availability issues, however, as the antifungal has not been licensed for use in 72 countries. Despite increasing resistance rates, fluconazole continues to be widely available, inexpensive, and suitable for treating many superficial fungal infections.
• Isavuconazole was approved for use in 2015, which was followed by a 10-fold increase in consumption in high-income countries and virtually no use in middle-income countries. Ketoconazole use decreased across the study period, perhaps partly due to warning labels about hepatotoxicity introduced in 2013.
• Access issues pose a significant risk to appropriate antifungal therapy, particularly for newer or more expensive antifungals. Extended-spectrum azoles (eg, voriconazole, isavuconazole, and posaconazole) with activity against Aspergillus are not licensed in many countries, have limited global availability, and are expensive. Due to rising azole resistance, echinocandins have been the preferred therapy for febrile neutropenia since 2016, but their availability is limited because of high costs and the lack of inclusion on the WHO’s Essential Medicines List.
• Although Amphotericin B (AmB) and flucytosine are important for treating cryptococcal meningitis in patients with HIV/AIDS, few changes in sales data were observed for the study period, a fact that the researchers attribute partly to high costs for both of the drugs and to high toxicity associated with the conventional (ie, not liposomal) AmB available in many lower-income countries. Additionally, AmB and flucytosine are unavailable in about 25% and 80% of countries worldwide, respectively.
• Given significant variation in antifungal use across national economies, along with disparities in affordability of lifesaving medicines, surveillance systems must begin to include fungal diseases in monitoring and reporting activities, and policy must ensure equitable global access to antifungals especially for immunocompromised patients.