Real‐World Use of Rezafungin for the Treatment of Challenging Aspergillus Infections

BACKGROUND: Aspergillus infections can pose significant treatment challenges, due in part to increasing triazole resistance. Clinical insight is needed to understand the potential for rezafungin, a next-generation echinocandin with once-weekly dosing, to address some limitations of current treatments for Aspergillus infections. METHODS: This retrospective case series collected anonymized real-world data from eight adults who received once-weekly rezafungin for difficult-to-treat Aspergillus infections. The cases were provided by clinicians in Spain, the UK, and Italy with considerable experience in treating challenging fungal infections. RESULTS: Most patients had pulmonary aspergillosis, nearly all had failed or were intolerant to triazole-based regimens, and half had prior echinocandin or amphotericin B exposure. Rezafungin was used primarily to enable outpatient parenteral antimicrobial therapy (OPAT), avoiding the need for daily IV echinocandin in settings of azole resistance or intolerance. About half received rezafungin as monotherapy; others had combination regimens. Clinical and/or radiological improvement or disease stabilization was observed in most cases, including in patients with azole-resistant infections. Notably, one patient achieved resolution of chronic otitis media, and others had negative cultures or sustained clinical benefit. Rezafungin was well tolerated, including in patients with renal impairment. One patient with chronic aspergilloma did not achieve adequate symptomatic control with rezafungin and required surgery. CONCLUSIONS: This report provides initial clinical insights on rezafungin as a potential option for difficult-to-treat Aspergillus infections. In this limited group of patients, rezafungin enabled OPAT, facilitated hospital discharge, and provided clinically meaningful improvements, including prolonged disease stabilization and resolution, which merit further investigation in clinical trials.