Molecular Alarm, Phenotypic Calm: A Rare Case of rpoB 511CCG Mutation in Tuberculosis with Review of Literature

Abstract Background: Rapid molecular diagnostics like GeneXpert Mycobacterium tuberculosis /RIF-Ultra are pillars of tuberculosis (TB) care but can detect “disputed” rpoB mutations, which confer low-level rifampicin resistance (RR) often missed by phenotypic drug susceptibility testing (DST). This genotypic–phenotypic discordance creates significant therapeutic uncertainty, especially in immunocompromised hosts. Case Presentation: A 54-year-old woman with seropositive rheumatoid arthritis on tofacitinib presented with cervical and mediastinal lymphadenopathy. Histopathology confirmed necrotizing granulomatous lymphadenitis. GeneXpert Ultra detected Mycobacterium TB complex with RR, prompting initiation of a multidrug-resistant TB (MDR-TB) regimen. Subsequent phenotypic DST (MGIT 960) revealed full susceptibility to all first-line drugs. Pyrosequencing identified the disputed rpoB 511CCG (Pro511Pro) mutation. Despite pan-susceptible DST, the MDR regimen was continued due to her profound immunosuppression, the risk of undertreatment, and alignment with World Health Organization guidance on such mutations. Conclusion: This case underscores the critical challenge of disputed rpoB mutations. In immunocompromised patients, erring on the side of caution by treating with an MDR regimen, even in the face of susceptible phenotypic results, may be a prudent strategy The patient achieved complete recovery after one year of anti tubercular treatment, with no evidence of relapse, supporting this approach despite initial diagnostic discordance.