Combination voriconazole and micafungin improved a boy with CGD and invasive Aspergillus lentulus infection

Aspergillus lentulus is a slow-growing and drug-resistant fungus, which has been primarily reported in adults, usually immunocompromised ones, suffering from invasive pulmonary aspergillosis (IPA). This condition is rare in children. Here, we report a case of invasive pulmonary aspergillosis due to Aspergillus lentulus in a boy with no history of recurrent infections who presented with a prolonged fever of unknown origin. Based on chest CT scan findings showing typical halo signs, a fungal infection was strongly suspected. Empirical antifungal therapy was initiated at early admission but failed to resolve the persistent fever in this case. The causative pathogen was confirmed by blood metagenomic next-generation sequencing (mNGS). Subsequent genetic analysis identified a pathogenic mutation in the X-linked CYBB gene, confirming chronic granulomatous disease (CGD). Eventually, following a combination therapy of voriconazole and micafungin, the boy became afebrile and was discharged, pending hematopoietic stem cell transplantation (HSCT). To our knowledge, no previous cases of Aspergillus lentulus infection in children with CGD have been reported in the literature. This case underscores the critical importance of identifying the causative microorganism. It also highlights the value of emerging detection methods, such as mNGS. At present, there is no consensus for the optimal antifungal regimen against pediatric Aspergillus lentulus infections. Clinical improvement was achieved in this patient following combination therapy with voriconazole and micafungin, offering a practical therapeutic reference for managing this refractory fungal infection.