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"tuberculosis"[MeSH Terms] AND "drug therapy"[MeSH Terms]
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Tuberculosis (TB) - Treatment & Drug Regimens
1. First-Line Drugs (RIPE / HRZE)
The four first-line anti-TB drugs and their standard adult doses:
| Drug | Daily Dose (max) | 3x/week DOT | 2x/week DOT | Key Side Effects |
|---|---|---|---|---|
| Isoniazid (INH/H) | 5 mg/kg (300 mg) | 15 mg/kg (900 mg) | 15 mg/kg (900 mg) | Hepatitis, peripheral neuropathy, drug interactions |
| Rifampin (RIF/R) | 10 mg/kg (600 mg) | 10 mg/kg (600 mg) | 10 mg/kg (600 mg) | Hepatitis, thrombocytopenia, GI upset, drug interactions |
| Pyrazinamide (PZA/Z) | 15-30 mg/kg (2 g) | 50 mg/kg (3 g) | 50 mg/kg (2 g) | Hepatitis, arthralgia, hyperuricemia |
| Ethambutol (EMB/E) | 15-20 mg/kg (1.6 g) | 25-30 mg/kg (2.5 g) | 50 mg/kg (2.5 g) | Retrobulbar neuritis, peripheral neuropathy |
(Source: Tintinalli's Emergency Medicine, Table 67-3)
2. Active TB Treatment (Drug-Susceptible)
Treatment has two phases: Intensive (8 weeks) + Continuation (18-31 weeks).
Standard 6-Month Regimen (Preferred)
Intensive phase (8 weeks): INH + RIF + PZA + EMB daily (7 days/week)
Continuation phase (18 weeks): INH + RIF daily
Alternative CDC-Approved Regimens
| Regimen | Intensive Phase | Continuation Phase | Notes |
|---|---|---|---|
| 1 (Preferred) | HRZE daily x 8 wk | HR daily x 18 wk | Preferred |
| 2 | HRZE daily x 8 wk | HR 3x/week x 18 wk | If less frequent DOT needed |
| 3 | HRZE 3x/week x 8 wk | HR 3x/week x 18 wk | Caution in HIV/cavitary disease |
| 4 | HRZE daily x 2 wk, then 2x/wk x 6 wk | HR 2x/week x 18 wk | Avoid in HIV/smear-positive/cavitary disease |
| 5 (3-drug fallback) | HRE daily x 8 wk | HR daily x 31 wk | When PZA not tolerated |
(Source: Tintinalli's Emergency Medicine, Katzung's Pharmacology)
Newer 4-Month Regimen (TBAJ-876 / TBTC Study 31)
- Intensive (8 wk): Rifapentine (RPT) + Moxifloxacin (MOX) + INH + PZA daily
- Continuation (9 wk): RPT + MOX daily
- Non-inferior to standard 6-month regimen for drug-susceptible pulmonary TB in persons ≥12 years old, weight ≥40 kg
(Source: Katzung's Basic and Clinical Pharmacology, 16th Ed.)
3. Key Principles
- Combination therapy is mandatory - monotherapy rapidly selects resistant mutants
- Direct Observed Therapy (DOT) is recommended for all twice- or thrice-weekly regimens, and when compliance is in doubt
- Fixed drug combination (FDC) tablets optimize effectiveness and reduce pill burden
- Modify therapy once culture sensitivity results are available
- Pyridoxine (Vitamin B6) should be co-administered with INH to prevent peripheral neuropathy
4. Prolonged Treatment Indications (extend to 9 months or longer)
- Immunocompromised patients (HIV, transplant recipients)
- Cavitary pulmonary TB with positive sputum culture at 2 months
- Extrapulmonary TB - especially CNS, disseminated, skeletal disease
- Drug-resistant TB
5. Hepatotoxicity Monitoring (Critical)
INH carries the highest hepatotoxicity risk (5-33% rate of transaminase elevation):
- Stop all anti-TB drugs if: AST/ALT >5x upper limit of normal, OR serum bilirubin >3 mg/dL
- Routine LFT monitoring required in: pre-existing liver disease, alcohol use, HIV, hepatitis C, pregnancy, other hepatotoxic drugs
6. Latent TB Infection (LTBI) Treatment
| Regimen | Duration | Frequency | Notes |
|---|---|---|---|
| INH alone | 9 months (preferred) | Daily or 2x/week | Preferred; 70% reduction in conversion risk |
| INH alone | 6 months | Daily | Not for HIV, fibrotic lesions, or children |
| Rifampin | 4 months | Daily | Alternative to INH |
| INH + Rifapentine (3HP) | 3 months | Once weekly | Preferred short course; useful when compliance is concern |
| INH + Rifapentine (1HP) | 1 month | Daily | HIV-infected adults ≥13 years only |
- LTBI treatment requires ruling out active TB first (clinical exam, CXR, sputum if indicated)
- Twice-weekly INH regimens must be DOT
- Preferred regimen in pregnancy: 9 months INH daily (in high-risk women)
(Source: Murray & Nadel's Respiratory Medicine, Table 42.4)
7. Drug-Resistant TB
Multidrug-Resistant TB (MDR-TB)
- Defined as resistance to at least INH and Rifampin
- Requires second-line drugs: fluoroquinolones (levofloxacin, moxifloxacin), injectable agents, etc.
- Duration: typically 18-20 months
XDR-TB / Treatment-Intolerant MDR-TB - The BPaL Regimen
The landmark all-oral 6-month regimen (Nix-TB trial):
Bedaquiline + Pretomanid + Linezolid (BPaL)
- Bedaquiline: Diarylquinoline, ATP synthase inhibitor - given orally
- Pretomanid: Nitroimidazooxazine - FDA approved 2019 for BPaL regimen
- Linezolid: Oxazolidinone antibiotic, repurposed for TB
Monitoring: Bedaquiline and pretomanid both carry QT prolongation risk - ECG monitoring required throughout therapy.
Recent meta-analyses (2025) confirm all-oral bedaquiline-based shorter regimens significantly improve treatment success rates for drug-resistant TB compared to older injectable-based regimens.
(Sources: Lippincott Pharmacology, Murray & Nadel, Harrison's Principles 22e)
8. Special Considerations
| Situation | Modification |
|---|---|
| HIV co-infection | Avoid rifapentine continuation; start ART; beware immune reconstitution (IRIS) |
| Pregnancy | Avoid PZA if possible; use HRE + pyridoxine; treat LTBI if high-risk |
| Hepatic disease | Reduce hepatotoxic drugs; monitor LFTs closely |
| Renal impairment | Adjust PZA and EMB doses (renally cleared) |
| Children | INH 10 mg/kg/day; doses differ - see CDC weight-based protocols |
Paradoxical Reaction / IRIS: A subset of patients worsen after starting treatment due to immune reconstitution. Features include fever, worsening infiltrates, lymphadenopathy, and hypercalcemia. This is more common in HIV patients with CD4 <50 cells/mm³. It must be distinguished from treatment failure or drug resistance.
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