A 32-year-old man from Delhi presents with a 3-week history of productive cough, fever, and night sweats. Chest X-ray shows cavitary lesions in the right upper lobe. Sputum smear microscopy is negative on two occasions. Which is the most appropriate next investigation to confirm tuberculosis?

## Investigation of Choice for TB Confirmation in Smear-Negative Cases **High-Yield:** GeneXpert MTB/RIF is the WHO-recommended rapid molecular test for TB diagnosis, especially when sputum smear microscopy is negative. It detects *Mycobacterium tuberculosis* DNA and rifampicin resistance in <2 hours. ### Why GeneXpert MTB/RIF is Superior Here | Feature | GeneXpert MTB/RIF | Sputum Culture | TST | CT Chest | |---------|-------------------|-----------------|-----|----------| | **Sensitivity (smear-negative TB)** | 90–95% | 80–90% | Variable | N/A | | **Turnaround time** | <2 hours | 2–8 weeks | 48–72 hours | Same day | | **Specificity** | >99% | 100% | Low (latent TB) | Non-specific | | **Detects rifampicin resistance** | Yes | Yes | No | No | | **Diagnostic utility** | Diagnostic | Diagnostic | Screening only | Supportive | **Key Point:** Sputum smear microscopy has only 40–60% sensitivity in pulmonary TB; GeneXpert MTB/RIF fills this diagnostic gap with rapid, high-sensitivity molecular detection. **Clinical Pearl:** In India, GeneXpert MTB/RIF is now the first-line test for all suspected TB cases per NTEP (National TB Elimination Programme) guidelines, replacing sputum microscopy as the initial confirmatory test. **Mnemonic: GXMR** — GeneXpert MTB/RIF: **G**old standard **X**-ray alternative, **M**olecular **R**apid test. ### Why Sputum Culture Is Not First-Line Here Although sputum culture remains the gold standard for TB diagnosis and drug susceptibility testing (DST), it takes 2–8 weeks, which delays treatment initiation in a symptomatic patient with cavitary disease and high clinical suspicion. ### Why TST and CT Are Inadequate - **Tuberculin skin test (Mantoux):** Screening tool only; does not differentiate active TB from latent TB infection; takes 48–72 hours for interpretation. - **High-resolution CT chest:** Supportive imaging (shows cavitation, bronchiectasis, nodules) but is not diagnostic and cannot differentiate TB from other cavitary diseases (fungal infection, malignancy, lung abscess).