Tuberculosis (TB)

Mycobacterium tuberculosis — cavitary pulmonary disease, hemoptysis, or isolation admission; notifiable disease; airborne transmission

Symptoms / Associated Sx

• Chronic productive cough (>2–3 weeks)

• Night sweats (drenching)

• Unintentional weight loss, anorexia, fatigue

• Low-grade fever (afternoon fevers — classic)

• Hemoptysis (cavitary disease — Rasmussen aneurysm, secondary aspergilloma in old cavities)

• Pleuritic chest pain (TB pleuritis)

• Extrapulmonary manifestations: lymphadenopathy, meningitis, vertebral osteomyelitis (Pott's disease), peritonitis, pericarditis

Denies

• Known TB treatment completion (treated, documented negative cultures — lowers active TB but does not exclude reactivation)

• No known TB contacts or endemic exposure (reduces likelihood but does not exclude — up to 25% of U.S. cases are reactivation)

• Normal CXR (active TB is very unlikely with normal CXR)

Social History (SHx)

Birth or travel in high-prevalence country (Asia, sub-Saharan Africa, Eastern Europe, Latin America), close contact with known active TB, immunosuppression (HIV — most important risk factor for progression; CD4 <200 → highest risk; TNF inhibitors, steroids, post-transplant), prior TB infection (LTBI) without treatment, homelessness, incarceration, alcohol/IV drug use, healthcare worker exposure.

Main Etiology

• Reactivation TB (most common in U.S.) — dormant LTBI reactivating due to immunosuppression (HIV, TNF inhibitors, steroids, aging)

• Primary progressive TB — new infection in immunocompromised or high-exposure settings

• MDR-TB (multi-drug resistant): resistance to isoniazid + rifampin; XDR-TB: additionally resistant to fluoroquinolone + second-line injectable

Most Common DDx

• Community-acquired pneumonia (acute presentation; responds to antibiotics; no cavitary disease; AFB smear negative; bilateral lower lobe more common)

• Lung cancer (upper lobe mass or cavitary lesion; weight loss; smoking history; bronchoscopy + biopsy; AFB smear negative; CT characteristic)

• NTM (Mycobacterium avium complex) (AFB positive but not M. tuberculosis; slower growing; Lady Windermere pattern; responds to MAC-specific 3-drug regimen)

• Aspergilloma in old TB cavity (hemoptysis without systemic symptoms; fungus ball in cavity; Aspergillus IgG elevated; BAE for bleeding control)

• Sarcoidosis (bilateral hilar adenopathy; non-caseating granulomas; elevated ACE; ANCA negative; AFB negative)

• Histoplasmosis/Coccidioidomycosis (endemic geographic area; fungal serology positive; Histoplasma urine antigen; no AFB)

DATA

• Sputum AFB smear × 3 (three consecutive morning specimens; high-quality sputum; ≥1 positive = presumptive TB → start treatment + isolation)

• Sputum NAAT (nucleic acid amplification test — Xpert MTB/RIF assay): detects TB DNA AND rifampin resistance within hours; sensitivity ~90% for smear-positive, ~65% for smear-negative; first-line rapid test

• Sputum mycobacterial culture (gold standard — takes 2–6 weeks; drug susceptibility testing)

• CXR (upper lobe infiltrates ± cavitation; fibrosis; ghon focus; lymphadenopathy — classic pattern; miliary pattern in disseminated TB)

• CT chest (better characterizes cavities, satellite lesions, endobronchial spread)

• HIV test (mandatory in all TB patients; co-infection changes management)

• TST (tuberculin skin test) or IGRA (interferon-gamma release assay — QuantiFERON-TB Gold; more specific than TST; not affected by BCG vaccination; does NOT distinguish active from latent TB)

• CBC (lymphopenia — HIV co-infection; pancytopenia — miliary TB)

• LFTs (hepatotoxicity monitoring — isoniazid, rifampin, pyrazinamide)

• BMP, uric acid (pyrazinamide — hyperuricemia; ethambutol — renal clearance)

• Visual acuity + color vision (ethambutol — optic neuritis monitoring)

• Bronchoscopy + BAL (if smear-negative and high suspicion; or miliary TB; or extrapulmonary)

• LP (if TB meningitis suspected — lymphocytic pleocytosis; elevated protein; low glucose; AFB smear + culture + NAAT)

Home Meds

• TNF inhibitors (hold immediately if active TB — risk of dissemination; restart only after TB treatment completion)

• Corticosteroids (immunosuppression — worsens TB; taper cautiously; TB meningitis is an exception where steroids are indicated)

• Antiretrovirals (HIV co-infection — drug interactions with rifampin; usually restart ART 2–8 weeks after TB therapy depending on CD4)

Plan

• Airborne isolation IMMEDIATELY on clinical suspicion (do not wait for smear/culture results):

  • Negative-pressure isolation room (≥12 air changes per hour)

  • N95 respirator for all healthcare workers entering room

  • Patient wears surgical mask when transported outside room

  • Maintain isolation until: 3 consecutive negative AFB smears + clinical improvement + effective TB therapy × ≥2 weeks

• RIPE therapy — standard initial treatment:

  • Rifampin (R) 10 mg/kg PO daily (max 600 mg) — most important bactericidal drug; orange urine/secretions (warn patient)

  • Isoniazid (I) 5 mg/kg PO daily (max 300 mg) + Pyridoxine (B6) 25–50 mg PO daily (prevents peripheral neuropathy)

  • Pyrazinamide (P) 25–35 mg/kg PO daily (max 2 g) — intensive phase only

  • Ethambutol (E) 15–25 mg/kg PO daily — until susceptibility results known (discontinue if susceptible to R+I)

  • Total duration: 6 months (2 months RIPE intensive phase → 4 months RI continuation phase)

  • MDR-TB: individualized regimen based on susceptibilities; ID/infectious disease specialist + public health; bedaquiline + linezolid-based regimens

• HIV co-infection:

  • Start TB therapy first; start ART within 2–8 weeks (2 weeks if CD4 <50; 8 weeks if CD4 >50)

  • Rifampin-based regimens interact with most PIs and NNRTIs — use efavirenz-based ART; dose adjustments required

  • Immune reconstitution inflammatory syndrome (IRIS) — paradoxical worsening after ART initiation; treat with NSAIDs or steroids

• TB meningitis: Rifampin + isoniazid + pyrazinamide + streptomycin (or ethambutol) × 2 months → R+I × 10 months; dexamethasone 0.3–0.4 mg/kg/day tapering over 6–8 weeks (reduces mortality)

• LFTs monthly (hepatotoxicity — stop RIPE if transaminases >3× ULN + symptoms or >5× ULN asymp)

• Visual acuity + color vision monthly (ethambutol)

• Repeat AFB smear + culture at 2 months (treatment response; culture conversion expected)

• Directly observed therapy (DOT) — mandatory for most active TB cases (public health responsibility)

• Public health reporting (mandatory notifiable disease — report within 24h)

• Contact tracing (public health)

• ID consult; pulmonology consult

• Trend LFTs monthly; CBC; uric acid; serum creatinine (ethambutol)

• PT/OT for prolonged hospitalization

• Discharge: DOT program enrollment (public health); complete 6-month course (adherence is critical for cure and resistance prevention); monthly LFTs + visual acuity; repeat sputum cultures; treat LTBI in close contacts; isolation at home until non-infectious (3 negative smears + clinical improvement); ID + pulmonology follow-up within 2 weeks

Red Flags

• Clinical suspicion for TB → airborne isolation BEFORE smear result; do not wait; one positive smear = treat

• Massive hemoptysis in TB → Rasmussen aneurysm (pulmonary artery erosion by cavity) → BAE emergently; bronchoscopy; thoracic surgery

• Miliary TB (diffuse bilateral millet-seed infiltrates) → disseminated; highest mortality; blood cultures + bone marrow biopsy; LP to rule out TB meningitis

• MDR-TB suspected (prior TB treatment, contact with MDR-TB, high-prevalence country) → DO NOT use standard RIPE empirically; await susceptibility results; ID/public health consult urgently

• TB meningitis (headache + meningismus + lymphocytic CSF in TB patient) → add steroids (dexamethasone) + LP urgently; high mortality if delayed

Senior IM Resident Pearls

• Xpert MTB/RIF (NAAT) is the fastest test for TB — results in 2h; high sensitivity in smear-positive patients; also detects rifampin resistance; order immediately when TB suspected; does not replace culture (needed for full drug susceptibilities)

• IGRA (QuantiFERON) does NOT distinguish active from latent TB — it detects TB sensitization; a positive IGRA in a patient with symptoms/CXR = active TB until proven otherwise; a negative IGRA does not rule out active TB (especially in immunosuppressed)

• Pyridoxine (B6) with isoniazid is mandatory — INH depletes B6 → peripheral neuropathy; 25–50 mg PO daily; especially important in HIV, diabetes, malnutrition, pregnancy, alcohol use

• Rifampin is a potent CYP enzyme inducer — reduces levels of many drugs: warfarin (increase dose dramatically), oral contraceptives (use barrier method), antiretrovirals (adjust doses), methadone (precipitate withdrawal), many others; always check drug interactions

• Common mistake: Delaying airborne isolation pending smear results — clinical suspicion alone mandates isolation; AFB smear sensitivity is only ~60–70%; a patient with cavitary TB is highly infectious even with initial negative smear

• Common mistake: Discharging a TB patient to home without DOT enrollment — nonadherence to TB treatment is the primary driver of MDR-TB; DOT ensures complete adherence and is a public health obligation