Beyond Adenosine Deaminase (ADA) and Mycobacterial Growth Indicator Tube (MGIT): The Utility of Xpert MTB/RIF Ultra for Diagnosis and Resistance Determination in Suspected Tubercular Pleural Effusion in a High-Burden State.

BACKGROUND: Diagnosis of tubercular pleural effusion (TPE) is difficult and always controversial unless proved microbiologically. Pleural fluid is almost always paucibacillary, leading to low microbiological yield. Physicians often rely on pleural fluid biochemistry and clinical judgment for initiating antitubercular therapy (ATT). Xpert Mycobacterium tuberculosis/rifampicin resistance Ultra (Xpert MTB/RIF Ultra) (Cepheid, Sunnyvale, CA) has been designed to ease the diagnostic dilemma and improve sensitivity in paucibacillary tuberculosis (TB). OBJECTIVES: This study aimed to evaluate the diagnostic utility of Xpert MTB/RIF Ultra in suspected TPE and assess its role in rifampicin resistance determination. METHODS: This retrospective observational study was conducted at a tertiary care center in Northern India. Patients with exudative lymphocytic pleural effusion, elevated adenosine deaminase levels, and clinic-radiological suspicion of TB who underwent pleural fluid Xpert MTB/ RIF Ultra and mycobacterial growth indicator tube (MGIT) culture testing were included. Clinical response to ATT and radiological improvement were assessed during follow-up. RESULTS: Twenty-one patients were included in the final analysis. Xpert MTB/RIF Ultra demonstrated positivity in 14 patients, while MGIT culture remained negative in all cases. All Ultra-positive patients showed significant clinical and radiological improvement following ATT, supporting the diagnosis of pleural TB despite MGIT culture negativity. Most of the Ultra-positive samples demonstrated "Trace" positivity with indeterminate rifampicin resistance results, limiting reliable drug resistance interpretation. CONCLUSION: Xpert MTB/RIF Ultra appears to be a useful adjunctive diagnostic tool in suspected TPE, where culture positivity is low. Although rifampicin resistance determination remains challenging in paucibacillary pleural fluid specimens, Ultra may help improve microbiological support for diagnosis alongside conventional clinical and biochemical assessment. Our findings correlate with the latest World Health Organization 2025 recommendations.