Disseminated Cryptococcosis in a Non-HIV Patient: Diagnostic Value of Integrating mNGS, Culture, and Antigen Testing

Abstract: Cryptococcus neoformans is an opportunistic fungal pathogen most commonly observed in individuals with human immunodeficiency virus (HIV) infection. Disseminated infections involving multiple organs, such as lungs, bloodstream, urinary tract, pleural cavity and central nervous system, are uncommon in patients without HIV. This work describes the case of a 72-year-old man who developed high fever and increased inflammatory markers after coronary artery bypass surgery. C. neoformans (8 sequence reads) was initially detected by metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid and was subsequently isolated from blood, urine and pleural effusion culture. Additionally, the cerebrospinal fluid tested positive for cryptococcal capsular polysaccharide antigen (CrAg), confirming disseminated infection involving multiple anatomical sites. The patient received liposomal amphotericin B combined with flucytosine antifungal treatment, which led to improvement in inflammatory parameters; however, the patient developed secondary multiorgan failure due to the severity of the illness. After 98 days of hospitalization, the patient was eventually discharged. This case highlights the diagnostic challenges of disseminated cryptococcosis in non-HIV hosts, particularly when involving atypical sites such as the urinary tract and pleural cavity. The integration of conventional microbiological methods, CrAg testing, and mNGS facilitated early diagnosis and enabled timely, standardized antifungal therapy. Keywords: disseminated cryptococcosis, non-human immunodeficiency virus, cryptococcal capsular polysaccharide antigen, metagenomic next-generation sequencing