Treatment of Tuberculosis (TB)

(Based on Harrison's Principles of Internal Medicine 22nd Ed. 2025, Tintinalli's Emergency Medicine, and Katzung's Pharmacology)

Classification of TB for Treatment Purposes

Type	Definition
Latent TB Infection (LTBI)	Positive TST/IGRA, no symptoms, normal CXR
Active Drug-Susceptible TB	Confirmed or presumed susceptible to first-line drugs
Drug-Resistant TB	MDR-TB (resistant to INH + RIF) or XDR-TB

I. Treatment of Latent TB Infection (LTBI)

(Regimens in order of current preference per CDC/NTCA 2020 guidelines)

Regimen	Dose	Duration	Notes
INH + Rifapentine (3HP)	INH 900 mg + RPT 900 mg weekly (wt >50 kg)	3 months	Preferred for adults and children >2 yr, including HIV+. Requires DOT for weekly dosing. Add pyridoxine 25-50 mg/d. NOT for pregnant women.
Rifampin (4R)	600 mg (10 mg/kg) daily	4 months	Preferred for HIV-negative; data limited in HIV+
INH + Rifampin (3HR)	INH 300 mg + RIF 600 mg daily	3 months	Higher hepatotoxicity risk vs individual drugs
Isoniazid (6H or 9H)	300 mg/d (5 mg/kg) or 900 mg twice weekly	6-9 months	9 months more effective but more hepatotoxic. Add pyridoxine. Twice-weekly requires DOT.

Shorter rifamycin-based regimens (4R or 3HR) are now preferred over 9H in most adults and children due to better effectiveness, safety, and tolerability.

II. Treatment of Active Drug-Susceptible TB

Standard 6-Month Regimen (Preferred)

Intensive phase (2 months): HRZE daily Continuation phase (4 months): HR daily

Phase	Drugs	Duration
Intensive	Isoniazid (H) + Rifampin (R) + Pyrazinamide (Z) + Ethambutol (E)	8 weeks
Continuation	Isoniazid (H) + Rifampin (R)	18 weeks

Total = 6 months (26 weeks)

Extend continuation phase to 7 months (total 9 months) if:

Cavitary pulmonary TB

2-month course of PZA not completed

Sputum culture positive at 2 months (delayed conversion)

Newer 4-Month Regimen (2022 - Non-inferior evidence)

A landmark multinational RCT (2020) showed a 4-month regimen is non-inferior to the standard 6-month regimen for drug-susceptible pulmonary TB in persons ≥12 years old weighing ≥40 kg:

Phase	Drugs	Duration
Intensive	Rifapentine + Moxifloxacin + Isoniazid + Pyrazinamide	8 weeks
Continuation	Rifapentine + Moxifloxacin + Isoniazid	9 weeks

Total = ~4 months (conditional recommendation, now included in Katzung 16th Ed.)

Adult Doses of First-Line Drugs

Drug	Daily (max)	3x weekly DOT (max)	2x weekly DOT (max)	Key Adverse 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 disturbance, drug interactions (CYP inducer)
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/optic neuritis, peripheral neuropathy
Rifabutin	5 mg/kg (300 mg)	Same	Same	Similar to RIF; used when RIF not tolerated (esp. HIV+ on ARTs)

Always give pyridoxine (B6) 25-50 mg/day with INH in: HIV, diabetes, alcoholism, malnutrition, pregnancy, renal failure.

DOT Scheduling Options (CDC)

Daily HRZE x 8 weeks → daily HR or HR/RPT x 18 weeks (preferred)
Daily HRZE x 2 weeks → twice-weekly x 6 weeks → HR/RPT 3x weekly x 18 weeks
Three-times-weekly HRZE x 8 weeks → HR 3x weekly x 18 weeks
Daily HIRE x 8 weeks → HR daily x 31 weeks (if PZA not used)

Twice- and thrice-weekly regimens must be given under DOT.

III. Drug-Resistant TB

MDR-TB (Resistant to INH + RIF)

WHO 2022 BPaL/BPaLM regimen (6-month all-oral):

Bedaquiline (B) + Pretomanid (Pa) + Linezolid (L) ± Moxifloxacin (M)
Duration: 6 months (BPaL) or 6 months (BPaLM if fluoroquinolone-susceptible)

Older longer regimens (18-24 months) are still used when newer drugs unavailable. Second-line drugs include:

Fluoroquinolones: levofloxacin, moxifloxacin (Group A)
Bedaquiline, linezolid (Group A)
Clofazimine (Group B)
Delamanid, pretomanid (Group C)
Injectable agents: amikacin, streptomycin (Group C - use with caution)

XDR-TB

Resistant to INH + RIF + any fluoroquinolone + at least one of bedaquiline or linezolid. Requires individualized regimens by expert consultation.

IV. Special Situations

Situation	Modification
HIV co-infection	Start TB Rx first; ART within 2-8 weeks (within 2 weeks if CD4 <50). Use rifabutin instead of rifampin with most PIs.
Pregnancy	HRZE is safe. Avoid streptomycin (ototoxic to fetus). Give pyridoxine.
Hepatic disease	Reduce number of hepatotoxic drugs; monitor LFTs closely.
CNS TB (meningitis)	2 months HRZE + 7-10 months HR. Add corticosteroids (dexamethasone).
Extrapulmonary TB	Generally same regimen; bone/joint and disseminated may need 9 months.
Paradoxical reaction/IRIS	Continue anti-TB drugs; consider NSAIDs or steroids; usually self-limiting.

V. Monitoring

LFTs: Baseline if risk factors (age >35, liver disease, alcohol, HIV, pregnancy/postpartum). Monthly if baseline abnormal.
Stop drugs if: symptomatic hepatitis + ALT/AST >3x ULN, or asymptomatic + ALT/AST >5x ULN, or bilirubin >3 mg/dL.
Visual acuity + color vision: Baseline and monthly for ethambutol (retrobulbar neuritis).
Sputum cultures: Monthly until negative; if still positive at 2 months, extend therapy and re-check susceptibilities.

Summary: First-Line Regimen at a Glance

Active DS-TB:  2HRZE / 4HR  (6 months total)
               Extend to 2HRZE / 7HR if cavitary or delayed conversion

LTBI (preferred): 3HP (INH + Rifapentine weekly x 3 months)
                  or 4R (Rifampin daily x 4 months)

Sources:

Harrison's Principles of Internal Medicine 22nd Ed. (2025), Chapter 186 - Antimycobacterial Agents
Tintinalli's Emergency Medicine, Chapter 67 - Table 67-3
Katzung's Basic and Clinical Pharmacology 16th Ed., Chapter on antimycobacterials

Recent evidence (2025): Two meta-analyses confirm bedaquiline-linezolid based regimens for MDR-TB show high success rates - PMID 40172415 and PMID 40194835 - supporting the current WHO move to all-oral shorter MDR-TB regimens.

This is a shared conversation. Sign in to Orris to start your own chat.