Abstract
BACKGROUND: Optimal antimicrobial strategies for disseminated nocardiosis with central nervous system (CNS) involvement remain poorly defined, particularly regarding trimethoprim-sulfamethoxazole (TMP-SMX) dosing in immunocompromised patients with severe drug intolerance. METHODS: This observational case study analyzed the clinical course and pharmacological management of a 55-year-old male gold miner with pneumoconiosis and chronic corticosteroid use who developed Nocardia farcinica brain abscess. Diagnosis was established via metagenomic next-generation sequencing (mNGS) and phenotypic culture. An individualized antimicrobial regimen was designed based on toxicity monitoring. RESULTS: Diagnosis of N. farcinica was confirmed by mNGS within 48 h. The patient initially failed empirical meropenem but responded to combination therapy with imipenem, amikacin, and TMP-SMX. Due to grade III gastrointestinal toxicity (CTCAE v5.0), TMP-SMX was de-escalated from 15 mg·kg(-1)·d(-1)-11.25 mg·kg(-1)·d(-1), with maintenance at 7.5 mg·kg(-1)·d(-1). Clinical improvement was observed at Day 120, though durable cure remains unconfirmed. CONCLUSION: In extreme circumstances of severe dose-limiting toxicity, temporary TMP-SMX dose reduction with intensive monitoring may be feasible as a bridge to complete guideline-concordant therapy, though this approach falls below current recommendations and requires robust therapeutic drug monitoring. Species-directed antimicrobial selection and early molecular diagnosis facilitated initial clinical resolution in this high-risk immunocompromised host.