How do you diagnose and treat pulmonary tuberculosis?

Ruling Out Pulmonary Tuberculosis

To rule out pulmonary TB, collect three sputum specimens for AFB smear microscopy, mycobacterial culture, and nucleic acid amplification testing (NAAT), combined with chest radiography—negative results on all three sputum specimens plus non-suggestive imaging effectively excludes active pulmonary TB in most cases. 1

Initial Diagnostic Approach

Sputum Collection and Testing

• Obtain three respiratory specimens (preferably early morning sputum on consecutive days) for AFB smear microscopy, mycobacterial culture, and NAAT (such as GeneXpert MTB/RIF) 1
• The first specimen has 53.8% sensitivity, the second adds 11.1%, and the third adds only 2-5% additional yield 1
• First morning specimens are 12% more sensitive than spot specimens 1
• Concentrated specimens increase sensitivity by 18% compared to non-concentrated specimens 1
• Fluorescence microscopy is 10% more sensitive than conventional microscopy 1

Imaging Studies

• Obtain chest radiography to assess for findings suggestive of TB, including upper lobe infiltrates, cavitation, or atypical patterns in immunocompromised patients 1
• CT imaging may be needed when chest radiograph is normal or inconclusive but clinical suspicion remains high 1, 2
• HIV-infected patients may show atypical patterns including lower lobe infiltrates, hilar adenopathy, or interstitial infiltrates rather than classic upper lobe cavitary disease 1

Rapid Molecular Testing

• NAAT (GeneXpert MTB/RIF) provides results within 1 day and simultaneously detects rifampin resistance 1
• GeneXpert has 96.3% sensitivity and 81.3% specificity in smear-negative cases when culture is the reference standard 3
• This test should be performed on at least one respiratory specimen from all patients with suspected pulmonary TB 1

When Initial Testing is Negative

Sputum Induction

• If patient cannot produce sputum spontaneously, perform sputum induction with hypertonic saline rather than proceeding directly to bronchoscopy 1
• Sputum induction has equal or greater diagnostic yield than bronchoscopy with fewer risks and lower cost 1

Bronchoscopy

• Perform flexible bronchoscopy if sputum cannot be obtained via induction or if high clinical suspicion persists despite negative induced sputum 1
• Bronchoscopic sampling (BAL, bronchial washings, brushings) has 50-100% diagnostic yield based on culture 1
• Transbronchial biopsy shows granulomas in 42-63% of smear-negative HIV-negative patients but only 9-19% of HIV-positive patients 1
• Bronchial washings have the same culture yield as BAL (95%) but higher AFB smear positivity (26% vs 4%) 1

Interpretation of Results

AFB Smear Microscopy

• Three AFB smears have approximately 70% sensitivity when culture-confirmed TB is the reference standard 1
• Specificity is ≥90%, but positive predictive value varies (70-90%) depending on local prevalence of nontuberculous mycobacteria 1
• A negative AFB smear does NOT exclude pulmonary TB—approximately 40% of culture-positive cases are smear-negative 1
• HIV-infected patients are less likely to have positive smears due to lower bacillary burden 1, 4

Culture Results

• Mycobacterial culture is the gold standard for diagnosis 1
• Liquid media cultures average 10-14 days, solid media average 3-4 weeks, with maximum time up to 6-8 weeks 1
• Culture provides isolates for drug susceptibility testing, which is essential for guiding treatment 1

NAAT Results

• Positive NAAT confirms Mycobacterium tuberculosis complex within 1 day 1
• Negative NAAT does not exclude TB, particularly in smear-negative cases 1
• GeneXpert detects rifampin resistance with >97% sensitivity and specificity 1

Clinical Decision-Making Algorithm

High Clinical Suspicion (persistent cough >2-3 weeks, fever, night sweats, weight loss, risk factors)

1. Collect three sputum specimens immediately for AFB smear, culture, and NAAT 1, 5
2. Obtain chest radiograph 1, 5
3. Perform HIV testing 5
4. If all three sputum specimens are AFB smear-negative AND NAAT-negative AND chest radiograph shows no findings suggestive of TB, consider sputum induction 1
5. If sputum induction is negative but suspicion remains high, proceed to bronchoscopy 1

Moderate Clinical Suspicion

1. Collect three sputum specimens for AFB smear, culture, and NAAT 1
2. Obtain chest radiograph 1
3. If all tests negative and radiograph normal, TB is effectively ruled out—consider alternative diagnoses 1
4. Continue clinical follow-up as culture results may take up to 6-8 weeks 1

Special Populations

• HIV-infected patients: Lower threshold for bronchoscopy due to atypical presentations and lower smear sensitivity 1
• Children: Consider gastric aspirates (three consecutive morning specimens) with yield up to 40-50% 1
• Immunocompromised hosts: More aggressive diagnostic approach including earlier bronchoscopy 1

Critical Pitfalls to Avoid

• Never rely on a single negative sputum specimen to exclude TB—three specimens are required 1
• Do not use TST or IGRA to exclude active TB disease—these tests detect latent infection, not active disease 1
• Do not assume negative AFB smears exclude TB—40% of culture-positive cases are smear-negative 1
• Do not delay empiric treatment in seriously ill patients while awaiting culture results if clinical suspicion is high 5
• Do not forget to collect specimens for culture and drug susceptibility testing before starting treatment, as this guides definitive therapy 1, 5
• Do not overlook atypical presentations in HIV-infected patients—they may lack classic upper lobe cavitary disease 1
• Do not stop evaluation after negative initial testing if clinical suspicion remains high—proceed to sputum induction or bronchoscopy 1

When TB is Effectively Ruled Out

Pulmonary TB can be considered effectively excluded when:

• All three sputum specimens are AFB smear-negative AND culture-negative AND NAAT-negative 1
• Chest radiograph shows no findings suggestive of TB 1
• Clinical symptoms resolve or alternative diagnosis is established 1
• In high-suspicion cases, bronchoscopy with BAL/biopsy is negative 1

However, maintain clinical vigilance: If symptoms persist or worsen despite negative initial workup, repeat testing or consider alternative sampling methods (sputum induction, bronchoscopy) 1, 5