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Tuberculosis
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Tuberculosis: Treatment & Drugs
Overview of Treatment Principles
TB treatment requires a combination of drugs to:
- Kill actively dividing bacilli rapidly
- Eliminate dormant/persisting bacilli to prevent relapse
- Prevent emergence of drug resistance
Treatment has two phases:
- Intensive phase - 4 drugs for 8 weeks (2 months)
- Continuation phase - 2 drugs for 18-31 weeks (4-7 months)
Direct Observed Therapy (DOT) is the standard of care, especially for intermittent regimens, to ensure adherence.
First-Line Drugs (RIPE)
The four first-line drugs are often remembered as RIPE (or HRZE):
| Drug | Daily Dose | Main Side Effects |
|---|---|---|
| Isoniazid (INH/H) | 5 mg/kg PO (max 300 mg) | Hepatitis, peripheral neuropathy, drug interactions |
| Rifampin (RIF/R) | 10 mg/kg PO (max 600 mg) | Hepatitis, thrombocytopenia, GI disturbance, drug interactions, orange discoloration of secretions |
| Pyrazinamide (PZA/Z) | 15-30 mg/kg PO (max 2 g) | Hepatitis, arthralgia, hyperuricemia |
| Ethambutol (EMB/E) | 15-20 mg/kg PO (max 1.6 g) | Retrobulbar neuritis, peripheral neuropathy, red-green color blindness |
Key note: Add pyridoxine (vitamin B6) with isoniazid to prevent peripheral neuropathy, especially in malnourished patients, pregnant women, diabetics, and alcoholics.
Standard Regimens for Drug-Susceptible Pulmonary TB
Preferred 6-month Regimen (Most Common)
- Intensive phase (8 weeks): INH + RIF + PZA + EMB daily
- Continuation phase (18 weeks): INH + RIF daily
Alternative schedules (all 6-9 months total):
- Daily 4-drug x 8 weeks → INH/RIF daily x 18 weeks (preferred)
- Daily 4-drug x 8 weeks → INH/RIF 3x/week x 18 weeks (preferred alternative when less frequent DOT is needed)
- 4-drug 3x/week x 8 weeks → INH/RIF 3x/week x 18 weeks (use with caution in HIV/cavitary disease)
- Daily 4-drug x 2 weeks → 2x/week x 6 weeks → INH/RIF 2x/week x 18 weeks (avoid in HIV or smear-positive/cavitary disease)
- Daily 3-drug (INH, RIF, EMB) x 8 weeks → INH/RIF x 31 weeks (when PZA cannot be used)
- Tintinalli's Emergency Medicine, p. 496
Newer 4-Month Regimen
- Rifapentine (RPT) + Moxifloxacin (MOX) + INH + PZA daily x 8 weeks
- Followed by RPT + MOX + INH daily x 9 weeks
- Non-inferior to the standard 6-month regimen for drug-susceptible pulmonary TB in patients ≥12 years old weighing ≥40 kg
- Katzung's Basic and Clinical Pharmacology, 16th Edition
Treatment of Latent TB Infection (LTBI)
Options include:
- 9 months of daily INH (gold standard - ~70% reduction in reactivation risk)
- 3 months of once-weekly INH + rifapentine (3HP) - useful when 9 months is unlikely to be completed
- 4 months of daily rifampin (4R)
- 3 months of daily rifampin + INH
- Tintinalli's Emergency Medicine, p. 496; Lippincott Illustrated Reviews: Pharmacology
Drug-Resistant TB
MDR-TB (resistant to at least INH + RIF)
Second-line drugs are used, including:
- Fluoroquinolones (levofloxacin, moxifloxacin)
- Aminoglycosides (amikacin, kanamycin)
- Cycloserine
- Linezolid
- Clofazimine
- Bedaquiline - ATP synthase inhibitor (oral)
XDR-TB / Treatment-Intolerant MDR-TB
The BPaL regimen (approved by FDA 2019):
- Bedaquiline + Pretomanid + Linezolid (6 months)
- Pretomanid is a nitroimidazooxazine with dual mechanisms of action
- Delamanid (similar class) is EMA-licensed for MDR-TB in Europe
- Lippincott Illustrated Reviews: Pharmacology; Murray & Nadel's Respiratory Medicine; Goodman & Gilman's
Important Monitoring & Side Effect Notes
| Drug | Key Toxicity to Monitor |
|---|---|
| INH | LFTs - stop if AST >5x ULN or bilirubin >3 mg/dL |
| Rifampin | LFTs, CBC (thrombocytopenia); orange urine/secretions (harmless) |
| Ethambutol | Monthly visual acuity + color vision testing |
| Pyrazinamide | Uric acid, LFTs |
Hepatotoxicity risk factors: pre-existing liver disease, pregnancy, alcohol use, HIV, hepatitis C - these patients need routine LFT monitoring.
Special Situations
| Situation | Modification |
|---|---|
| HIV co-infection | Start ART; avoid twice/thrice-weekly regimens; rifabutin may replace rifampin if on protease inhibitors |
| Cavitary TB with positive 2-month culture | Extend continuation phase |
| CNS/Disseminated/Skeletal TB | Prolonged therapy |
| Pregnancy | Avoid pyrazinamide in some guidelines; avoid aminoglycosides |
| Paradoxical reaction / IRIS | Seen especially in HIV with CD4 ≤50 - fever, worsening infiltrates, lymphadenopathy, hypercalcemia (distinguish from treatment failure) |
Recent Evidence (2024-2026)
A 2026 practice guideline for tuberculous meningitis was published in Lancet Infectious Diseases [PMID: 40840485] - this may update management specifics for CNS TB. A 2024 meta-analysis highlighted [PMID: 38346381] that TB-diabetes comorbidity significantly complicates treatment adherence and outcomes, warranting closer monitoring in diabetic patients.
Summary in one sentence: Drug-susceptible TB is treated with HRZE for 2 months, then HR for 4 months (total 6 months); resistant TB uses second-line agents, with the BPaL regimen (bedaquiline + pretomanid + linezolid) for XDR-TB.
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