Drug-Resistant Tuberculous Meningitis (DR-TBM) in a Low-Incidence Setting: Two Cases and an Evidence Review Highlighting Key Advances and Knowledge Gaps in Clinical Management

Abstract We report on 2 patients with drug-resistant tuberculous meningitis diagnosed and treated in a high-resource, low-incidence setting. Both patients were treated with multidrug regimens including bedaquiline, a nitroimidazole, cycloserine, and linezolid. Drug selection was informed by molecular diagnostics, susceptibility testing, and pharmacokinetic and clinical data. Adverse events included suicidal ideation, cytopenias, ototoxicity, and neuropathy. There was discordance between phenotypic (susceptible) and genotypic (resistant) drug susceptibility testing for rifampin. After treatment, both patients had excellent clinical outcomes, with at least 12 months of post-treatment follow-up. These clinical cases provide an opportunity to explore the role of molecular diagnostics in the diagnosis of drug-resistant tuberculous meningitis, drug regimen selection in the era of novel oral regimens, and clinical decision-making in the setting of discordance between genotypic and phenotypic drug susceptibility testing.