BACKGROUND AND OBJECTIVES: Fungal infections cause substantial morbidity and mortality. Monitoring antifungal use is a foundational aspect of antifungal stewardship, particularly as new disease-causing fungi emerge and antifungal resistance spreads. We assessed recent patterns in systemic antifungal medication use among hospitalized patients within a diverse convenience sample of academic medical centres and community hospitals in the USA. METHODS: We conducted a multicentre retrospective cohort study using the Vizient(R) Clinical Data Base. We selected hospitalized patients who received >/=1 dose of systemic antifungal medication during 2018-23 and assessed antifungal days of therapy (DOT) per 1000 patient days. We stratified antifungal DOT by National Comprehensive Cancer Network (NCCN) cancer centre status to compare antifungal use at hospitals with an NCCN-designated cancer centre-some of which also include a main academic medical centre and non-cancer service lines-versus hospitals without an NCCN-designated cancer centre. RESULTS: Among 39 956 873 discharges from 412 hospitals, the proportion of patients who received any systemic antifungal was 4.5%; azoles (3.8%) were the most common antifungal class, followed by echinocandins (0.9%). Overall antifungal DOT were 53.7 per 1000 patient days (114.5 among 25 NCCN hospitals and 43.2 among 387 non-NCCN hospitals). CONCLUSIONS: Substantial antifungal use occurs among hospitalized patients, particularly among those with cancer. The growing population susceptible to fungal infections (e.g. transplants, cancer and other immunosuppressing conditions) warrants consideration of antifungal stewardship and evaluation of appropriateness of antifungal use in the context of increasing resistance.

A 46-year-old man with relapsed acute myeloid leukemia underwent his second matched related donor stem cell transplant (SCT), after fludarabine and melphalan conditioning followed by post-transplant cyclophosphamide. He engrafted on day +20. On day +27, he developed fever, sinusitis, left eyelid swelling, and right eye subconjunctival swelling (Figure 1A). He required an urgent right vitrectomy for endophthalmitis. Seven days later, he developed skin nodules on his upper and lower extremities which progressively enlarged and became more diffuse (Figure 1Band 1C). Laboratory tests showed leukopenia (white blood cell count 3.1 × 109/L), anemia (Hb 7.2 g/dL), and severe thrombocytopenia (25 × 109/L) with normal electrolytes, and normal renal and hepatic function. Blood, urine, and sputum cultures were no growth, and infectious serologies, nucleic acid, and antigen tests were negative, including for human immunodeficiency virus, syphilis, Toxoplasma, tuberculosis, cytomegalovirus, and Strongyloides. Nasal endoscopy did not demonstrate necrosis of sinus tissue, and sinus swab cultures did not grow any organisms of clinical significance. Wide excisional skin biopsies of skin lesions demonstrated a lymphohistiocytic infiltrate and panniculitis (Figure 2A) and circular structures (Figure 2B). Vitrectomy was performed for endophthalmitis, and vitreous fluid cultures had no growth. Positron emission tomography (PET) demonstrated diffuse subcutaneous foci most numerous of the lower extremities, and a left occipitotemporal focus (Figure 3A). Shortly thereafter, he developed acute encephalopathy, drowsiness, and rhythmic movements of his right arm concerning for seizures. Brain magnetic resonance imaging (MRI) demonstrated abnormalities of the left frontal gyrus, occipital lobe, parieto-occipital sulcus, and cerebellum, concerning for embolic strokes (Figure 3B). He continued to have fever and progression of skin lesions despite treatment with meropenem, vancomycin, minocycline, and amphotericin. What is the likely diagnosis?