Although nebulized liposomal amphotericin B (NLAB) is being used in invasive pulmonary aspergillosis (IPA) prophylaxis, no clinical trial has shown its efficacy as a therapeutic strategy. NAIFI is the inaugural randomized, controlled clinical trial designed to examine the safety and effectiveness of NLAB (dosage: 25 mg in 6 mL, three times per week for 6 weeks) against a placebo, in the auxiliary treatment of IPA. Throughout the three-year clinical trial, thirteen patients (six NLAB, seven placebo) were included, with 61% being onco-hematological with less than 100 neutrophils/μL. There were no significant differences noted in their pre- and post-nebulization results of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and oxygen saturation between the groups. Neither bronchospasm nor serum amphotericin B levels were reported in any patients given NLAB. ¹⁸F-Fluorodeoxyglucose positron emission tomography (FDG-PET-TC) was carried out at the baseline and after 6 weeks. A notable decrease in median SUV (standardized uptake value) was observed in NLAB patients after 6 weeks (−3.6 vs. −0.95, p: 0.039, one tail). Furthermore, a reduction in serum substance galactomannan and beta-D-Glucan was identified within NLAB recipients. NLAB is well tolerated and safe for patients with IPA. Encouraging indirect efficacy data have been derived from image monitoring or biomarkers. However, further studies involving more patients are necessary.

Background: Aspergillus endocarditis is a rare but life-threatening form of infective endocarditis that typically occurs in patients with a history of cardiac surgery, prosthetic valve implantation, or profound immunosuppression. Native valve involvement in non-traditional hosts remains exceptionally rare and is diagnostically challenging. Case presentation: We describe a 56-year-old woman with CREST syndrome and advanced liver disease awaiting transplantation who developed native aortic valve endocarditis. Blood cultures and serum biomarkers (galactomannan and β-d-glucan) were also negative. Transthoracic echocardiography revealed vegetation on the aortic valve. Valve replacement was performed, and Aspergillus fumigatus was isolated from two valve cultures. Liposomal amphotericin B was initiated; however, the patient died of multiorgan failure two weeks later. Systematic review: To contextualise this case, we conducted a systematic review of the literature following the PRISMA guidelines. We included microbiologically confirmed cases of native valve Aspergillus endocarditis based on valve or embolic tissue analysis. Forty-three studies met the inclusion criteria, comprising 45 patients in total. Data were independently extracted by two reviewers and narratively synthesised due to clinical heterogeneity. Conclusions: This case illustrates the diagnostic and therapeutic challenges of native-valve Aspergillus endocarditis in patients without classical risk factors for the disease. Early imaging and a high index of suspicion are crucial for diagnosis. Combined surgical and antifungal therapy remains the cornerstone of management, although the mortality rate remains high.