Utility of clinical metagenomics in complex infections: Cryptococcal meningitis complicated by Nocardia brain abscess

Abstract

Nocardia farcinica brain abscess (BA) is a rare yet life-threatening infection of the central nervous system (CNS) that predominantly affects immunocompromised patients. Its nonspecific symptoms often lead to delayed diagnosis and poor outcomes. Early diagnosis and precise treatment are essential to improve the prognosis of patients. We report the rare case of a 75-year-old man with IgG4-related disease undergoing long-term methylprednisolone therapy who presented with a N. farcinica brain abscess. The patient initially presented with cryptococcal meningitis but exhibited persistent symptoms despite standard antifungal treatment. Follow-up neuroimaging revealed new intracranial abscess formations. Metagenomic next-generation sequencing (mNGS) of brain tissue and cerebrospinal fluid (CSF) identified abundant N. farcinica-specific sequences, confirming a concurrent Nocardia brain abscess complicating the cryptococcal infection. The patient's condition gradually improved with timely antibiotic treatment and is currently in recovery. This case underscores the heightened risk of sequential opportunistic infections in immunocompromised individuals and exemplifies the clinical value of mNGS in detecting rare infectious diseases. We further conducted a systematic review of patients with Nocardia central nervous system infections confirmed by mNGS, analyzing their clinical presentations, laboratory parameters, therapeutic regimens, and prognostic outcomes. In summary, our study demonstrates that mNGS offers significant diagnostic advantages compared to conventional microbiological methods for uncommon infections. These findings provide clinically actionable, evidence-based guidance for the diagnosis and management of Nocardia brain abscesses.

Keywords: Brain abscess; Cryptococcal meningitis; Immunodeficiency; Metagenomic next-generation sequencing; Nocardia farcinica.