Although several new antifungal drugs have been licensed in the last 5 years, some patients remain difficult to treat. The main reasons for this include intrinsic or acquired antifungal resistance, organ dysfunction preventing the use of some agents and drug interactions. In addition, some drugs penetrate poorly into sanctuary sites including eye and urine, and others are associated with considerable adverse events. Here, we review the preclinical and clinical development progress with four new antifungal agents: isavuconazole, ravuconazole, albaconazole and aminocandin. Isavuconazole and ravuconazole are extremely similar, with a broad spectrum of activity, a very long half-life and large volume of distribution and good in vivo data supporting their efficacy in invasive aspergillosis and candidosis. Both compounds are in early Phase 3 development. Albaconazole has also shown very potent activity against species of Candida, Cryptococcus and Aspergillus. It was well tolerated and effective in women with vaginal candidosis. Aminocandin is an intravenous-only echinocandin with in vivo activity against Candida spp. and Aspergillus spp. Its extended half-life probably permits dosing less frequently than once a day. Overall these new antifungal agents in development offer extended half-lives, possibly reduced drug interaction profiles and good tolerance. Their antifungal spectrum is narrower than posaconazole and probably similar to voriconazole (isavuconazole and ravuconazole) and caspofungin (aminocandin). Licensure and determination of their place in clinical practice requires randomized clinical studies, which are or will be underway.

Histoplasmosis is highly endemic in the American continent. This condition is associated with a high mortality, particularly in people living with HIV/AIDS (PLWHA). Diagnosis of histoplasmosis is usually late in South America, as Histoplasma antigen detection is rarely available. Here we determined the prevalence, risk factors, and outcome of histoplasmosis in PLWHA in Brazilian hospitals. This was a prospective cohort study (2016-2018) involving 14 tertiary medical centers in Brazil. We included hospitalized PLWHA presenting with fever and additional clinical findings. Patients were investigated at each participant center with classical mycology methods. Also, Histoplasma antigen detection was performed in urine samples (IMMY). Probable/proven histoplasmosis was defined according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group/National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria. From 616 eligible patients, 570 were included. Histoplasmosis was identified in 21.6% (123/570) of patients. Urine antigen testing increased the diagnostic yield in 53.8%, in comparison with standard mycology methods. Variables independently associated with histoplasmosis were CD4+ count <50 cells/mm³, use of an antiretroviral (protective effect), and sample collection in the Northeast region of Brazil. Dyspnea at presentation was independently associated with death. Histoplasmosis was more frequent than tuberculosis in patients with low CD4+ counts. Overall 30-day mortality was 22.1%, decreasing to 14.3% in patients with antigen-based diagnosis. Histoplasmosis is a very frequent condition affecting PLWHA in Brazil, particularly when CD4+ counts are lower than 50 cells/mm³. Antigen detection may detect earlier disease, with a probable impact on outcomes. Access to this diagnostic tool is needed to improve clinical management of PLWHA in endemic countries.

Africa, although not unique in this context, is a favourable environment for fungal infections, given the high burden of risk factors. An online survey was developed asking about laboratory infrastructure and antifungal drug availability. We received 40 responses (24·4% response rate) of 164 researchers contacted from 21 African countries. Only five institutions (12·5%) of 40 located in Cameroon, Kenya, Nigeria, Sudan, and Uganda potentially fulfilled the minimum laboratory requirements for European Confederation of Medical Mycology Excellence Centre blue status. Difficulties included low access to susceptibility testing for both yeasts and moulds (available in only 30% of institutions) and Aspergillus spp antigen detection (available in only 47·5% of institutions as an in-house or outsourced test), as well as access to mould-active antifungal drugs such as amphotericin B deoxycholate (available for 52·5% of institutions), itraconazole (52·5%), voriconazole (35·0%), and posaconazole (5·0%). United and targeted efforts are crucial to face the growing challenges in clinical mycology.

Corticosteroids have potent anti-inflammatory and immunosuppressive effects. Recently, these medications have gained importance in the treatment of severe COVID-19. Here we present data demonstrating a marked (10-fold) increase in frequency of candidemia in hospitalized patients with COVID-19 receiving corticosteroids in Brazil. Overall mortality was 72.7%, despite antifungal therapy. Physicians should be aware of the potential risk for candidemia among severely ill COVID-19 patients receiving high-doses of corticosteroids.