Tuberculosis treatment
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"tuberculosis"[MeSH Terms] AND "drug therapy"[MeSH Terms]
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Tuberculosis Treatment
Overview
TB treatment requires combination drug therapy because monotherapy rapidly selects resistant mutants. The regimen is divided into two phases: an intensive phase that kills actively dividing bacilli, and a continuation phase that eliminates persistent organisms and prevents relapse. - Murray & Nadel's Textbook of Respiratory Medicine
1. Drug-Susceptible Pulmonary TB
Standard 6-Month Regimen (Preferred)
Intensive Phase (8 weeks): HRZE
- Isoniazid (INH) 300 mg/day
- Rifampin (RIF) 600 mg/day
- Pyrazinamide (PZA) 15-30 mg/kg/day
- Ethambutol (EMB) 15-20 mg/kg/day
Continuation Phase (18 weeks): INH + RIF daily (or INH + rifapentine)
This regimen achieves cure in >95% of drug-susceptible cases when completed. - Tintinalli's Emergency Medicine
Newer 4-Month Regimen (HRZE + Moxifloxacin)
Shown non-inferior to the standard 6-month regimen for drug-susceptible pulmonary TB in persons ≥12 years weighing ≥40 kg:
| Phase | Drugs | Duration |
|---|---|---|
| Intensive | Rifapentine + Moxifloxacin + INH + PZA | 8 weeks daily |
| Continuation | Rifapentine + Moxifloxacin + INH | 9 weeks daily |
- Katzung's Basic and Clinical Pharmacology, 16th Ed.
Dosing Options
| Drug | Daily | 3x/week DOT | 2x/week DOT |
|---|---|---|---|
| Isoniazid | 5 mg/kg (max 300 mg) | 15 mg/kg (max 900 mg) | 15 mg/kg (max 900 mg) |
| Rifampin | 10 mg/kg (max 600 mg) | 10 mg/kg (max 600 mg) | 10 mg/kg (max 600 mg) |
| Ethambutol | 15-20 mg/kg (max 1.6 g) | 25-30 mg/kg | 50 mg/kg |
| Pyrazinamide | 15-30 mg/kg (max 2 g) | 50 mg/kg (max 3 g) | 50 mg/kg (max 2 g) |
- Tintinalli's Emergency Medicine, Table 67-3
2. Directly Observed Therapy (DOT)
DOT is strongly recommended by the CDC, especially for:
- All twice-weekly or thrice-weekly regimens (mandatory DOT)
- Patients with compliance concerns
- Drug-resistant TB cases
DOT significantly reduces relapse and secondary resistance development. - Tintinalli's Emergency Medicine
3. Extended Treatment Indications
Prolonged therapy (up to 9 months total) is used for:
- Immunocompromised patients (HIV, transplant, steroids)
- Cavitary pulmonary TB with positive sputum culture after 2 months
- Extrapulmonary TB: disseminated, CNS, skeletal
- Drug-resistant TB
4. Key Drug Mechanisms & Adverse Effects
| Drug | Mechanism | Key Adverse Effects |
|---|---|---|
| Isoniazid | Prodrug activated by KatG; inhibits mycolic acid synthesis (InhA) | Hepatitis (5-33%), peripheral neuropathy - give pyridoxine 25-50 mg/day |
| Rifampin | Inhibits bacterial RNA polymerase | Hepatitis, thrombocytopenia, GI disturbance, strong CYP inducer (many drug interactions) |
| Pyrazinamide | Bactericidal in acidic environment (within macrophages) | Hepatitis, arthralgia, hyperuricemia |
| Ethambutol | Inhibits arabinosyl transferase (cell wall synthesis) | Retrobulbar/optic neuritis (dose-related), peripheral neuropathy |
| Rifapentine | Same as rifampin (long-acting) | Hepatitis, thrombocytopenia, porphyria exacerbation |
Monitor LFTs if: preexisting liver disease, alcohol use, pregnancy, HIV, hepatitis C. Stop anti-TB medications if AST >5x ULN or bilirubin >3 mg/dL. - Harrison's Principles of Internal Medicine 22E
5. Drug-Resistant TB
Definitions
- MDR-TB: Resistant to at least INH + rifampin
- XDR-TB: MDR-TB + resistant to a fluoroquinolone + at least one injectable second-line drug
BPaLM Regimen (WHO, 2022 - now preferred for MDR/XDR-TB)
- Bedaquiline + Pretomanid + Linezolid + Moxifloxacin
- 6-month all-oral regimen
- Recent meta-analyses (2025) confirm bedaquiline + linezolid-based regimens achieve high treatment success for MDR-TB
Second-Line Drugs (for DR-TB)
| Drug | Typical Adult Dose |
|---|---|
| Bedaquiline | 400 mg/day (first 2 wks), then 200 mg 3x/wk |
| Pretomanid | 200 mg/day |
| Linezolid | 600 mg/day |
| Moxifloxacin | 400 mg/day |
| Levofloxacin | 750-1000 mg/day |
| Amikacin | 15 mg/kg/day (injectable) |
| Cycloserine | 500-1000 mg/day divided |
| Ethionamide | 500-750 mg/day |
| Rifabutin | 300 mg/day (used when rifampin not tolerated) |
| Aminosalicylic acid | 8-12 g/day |
- Katzung's Basic and Clinical Pharmacology, 16th Ed.
Risk factors for drug resistance: prior TB treatment, residence in high-prevalence area, known MDR-TB contact. - Tintinalli's Emergency Medicine
6. Latent TB Infection (LTBI) Treatment
| Regimen | Duration | Frequency | Notes |
|---|---|---|---|
| INH alone | 9 months (preferred) | Daily or twice-weekly | 70% reduction in reactivation risk |
| INH alone | 6 months | Daily | Not for HIV, children, or fibrotic lesions |
| Rifampin | 4 months | Daily | Good alternative to INH |
| INH + Rifapentine (3HP) | 3 months | Once weekly | Preferred short-course; DOT or self-administered |
| INH + Rifapentine (1HP) | 1 month | Daily | HIV-infected adults ≥13 years |
Shorter rifamycin-based regimens are preferred to improve adherence. Nine months of daily INH is preferred in pregnant women at high risk for progression. - Murray & Nadel's Textbook of Respiratory Medicine
Treatment for LTBI reduces reactivation risk by approximately 70%. Before starting, always exclude active TB with history, exam, chest X-ray, and sputum testing if indicated. - Tintinalli's Emergency Medicine
7. Special Populations
| Population | Key Considerations |
|---|---|
| HIV co-infection | Start ART; manage rifampin drug interactions; use lower TST cut-points; consider empiric LTBI treatment even with negative IGRA if CD4 <200 |
| Pregnancy | Avoid PZA in some guidelines (1st trimester); 9-month INH preferred for LTBI in high-risk pregnant women; avoid streptomycin (ototoxicity to fetus) |
| Children | Weight-based dosing; 3HP regimen approved ≥2 years; 1HP not recommended <2 years |
| Liver disease | Monitor LFTs closely; may need to modify or substitute hepatotoxic agents |
| CNS/miliary TB | Extend treatment to 9-12 months; add corticosteroids for TB meningitis |
8. Immune Reconstitution Inflammatory Syndrome (IRIS)
In HIV+ patients starting both ART and TB treatment, paradoxical IRIS may develop - worsening symptoms (fever, lymphadenopathy, pulmonary infiltrates, hypercalcemia) due to immune recovery. Distinguish from treatment failure or resistance by clinical context and drug susceptibility testing. - Tintinalli's Emergency Medicine
Recent Evidence (2025)
Two recent meta-analyses support the current trend toward all-oral bedaquiline-based shorter regimens for drug-resistant TB:
- Bedaquiline + linezolid meta-analysis (PMID 40172415) - confirms efficacy of this combination for MDR-TB
- All-oral bedaquiline shorter regimens meta-analysis (PMID 40194835) - demonstrates high treatment success rates, supporting global shift away from injectables
These findings align with WHO 2022 consolidated guidelines, which now prioritize all-oral regimens and have moved injectables to Group C (used only when others cannot be composed).
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