Guidelines for Tuberculosis Treatment
Drug-Susceptible Pulmonary TB: Standard 6-Month Regimen
For newly diagnosed drug-susceptible pulmonary tuberculosis, treat with a 6-month regimen consisting of isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months (intensive phase), followed by isoniazid and rifampin for 4 months (continuation phase). 1
Intensive Phase (First 2 Months)
- Four drugs administered daily or 5 days/week: isoniazid, rifampin, pyrazinamide, and ethambutol 1
- Ethambutol (or streptomycin) should be added as the fourth drug unless isoniazid resistance in the community is documented to be less than 4% 1, 2
- Total doses: 56 doses over 8 weeks if given daily, or 40 doses if given 5 days/week 1
Continuation Phase (Next 4 Months)
- Two drugs: isoniazid and rifampin 1
- Can be administered daily (7 days/week for 126 doses) or intermittently (3 times weekly for 54 doses, or twice weekly for 36 doses) 1
- Caution: Twice-weekly regimens should NOT be used in HIV-infected patients or those with smear-positive/cavitary disease 1
Directly Observed Therapy (DOT)
- Strongly recommended for all patients, particularly when drugs are given less than 7 days per week 1, 3
- DOT involves observing the patient swallow each dose of medication 1
Drug-Resistant TB: Longer Oral Regimens
For multidrug-resistant TB (MDR-TB), use an all-oral regimen with at least 5 effective drugs in the intensive phase and 4 drugs in the continuation phase, with total treatment duration of 15-24 months after culture conversion. 1, 4
Core Drugs for MDR-TB (Must Include)
- Bedaquiline (strong recommendation) 1, 4
- Later-generation fluoroquinolone (levofloxacin or moxifloxacin) (strong recommendation) 1, 4
- Linezolid (strong recommendation) 1, 4
Additional Drugs to Reach 5-Drug Regimen
- Clofazimine (conditional recommendation) 1, 4
- Cycloserine (conditional recommendation) 1, 4
- Pyrazinamide when susceptibility confirmed (conditional recommendation) 1, 4
- Delamanid for patients ≥3 years (conditional recommendation) 1, 4
Drugs NOT to Include in MDR-TB Regimens
- Do NOT use: amoxicillin-clavulanate (except with carbapenems), macrolides (azithromycin/clarithromycin), kanamycin, or capreomycin 1, 4
- Avoid if possible: ethionamide/prothionamide and p-aminosalicylic acid (use only if cannot construct 5-drug regimen otherwise) 1, 4
Injectable Agents (Use Only When Necessary)
- Amikacin or streptomycin may be included only when susceptibility is confirmed and no better oral options exist 1, 4
- Carbapenems (imipenem or meropenem) must always be combined with amoxicillin-clavulanate 1, 5
Treatment Duration for MDR-TB
- Intensive phase: 5-7 months after culture conversion 1
- Total duration: 15-21 months after culture conversion for MDR-TB 1
- For pre-XDR and XDR-TB: 15-24 months after culture conversion 1
Shorter Regimen for MDR-TB: BPaLM
For eligible MDR/rifampin-resistant TB patients, the 6-month BPaLM regimen (bedaquiline, pretomanid, linezolid, moxifloxacin) is an effective alternative to longer regimens. 6
Eligibility Criteria
- Confirmed MDR/rifampin-resistant TB (including extrapulmonary disease) 6
- No documented resistance to fluoroquinolones or bedaquiline 6
- Duration: 6 months total 6
Isoniazid-Resistant TB
For isoniazid-resistant TB (with rifampin susceptibility), use a 6-month regimen of rifampin, ethambutol, pyrazinamide, and a later-generation fluoroquinolone. 6
Special Populations
HIV-Infected Patients
- Use same initial 4-drug regimen as HIV-negative patients 1
- Do NOT use twice-weekly or thrice-weekly regimens 1
- Start antiretroviral therapy within first 8 weeks of TB treatment 4
- For drug-resistant TB with HIV: extend treatment to at least 9 months and for at least 6 months beyond culture conversion 6
Pregnant Women
- Do NOT use streptomycin (causes congenital deafness) 1
- Avoid pyrazinamide due to inadequate teratogenicity data 1
- Initial regimen: isoniazid, rifampin, and ethambutol 1
Children
- Same drug regimens as adults with weight-based dosing 1, 2
- Isoniazid: 10-15 mg/kg daily (max 300 mg) or 20-40 mg/kg 2-3 times weekly (max 900 mg) 2
- Rifampin: 10-20 mg/kg daily (max 600 mg) 7
- Avoid ethambutol in young children whose visual acuity cannot be monitored 1
Critical Management Principles
Drug Susceptibility Testing
- Obtain cultures and susceptibility testing before starting treatment in 90% of adults (50% of children) 1
- Molecular DST should be performed for rapid detection of resistance mutations 1
- When rifampin resistance detected, immediately test for fluoroquinolone and aminoglycoside resistance 1
Monitoring Treatment Response
- Monthly sputum cultures to monitor treatment response 6, 4
- Patients who remain smear-positive at 3 months require reevaluation for nonadherence or drug resistance 1
Critical Pitfall to Avoid
NEVER add a single drug to a failing regimen - this creates de facto monotherapy and leads to acquired resistance 1, 4
- When treatment failure suspected, add ≥2 new drugs to which the organism is susceptible 1
Case Management and Adherence Support
- Assign a public health case manager to develop individualized treatment plan 1
- Provide patient education about TB, treatment duration, and expected outcomes 1
- Use incentives, enablers, field visits, and digital monitoring to support adherence 1, 6, 4
Reporting Requirements
- Report all TB cases to local/state health department within 1 week of diagnosis 1
Expert Consultation
- Consult TB expert when drug resistance is suspected or confirmed 1
- In the United States, experts available through CDC TB Centers of Excellence 1
Latent TB Infection (LTBI)
Treat all persons with latent TB infection unless prior treatment documented. 1
Recommended LTBI Regimens
- Preferred: 9 months of isoniazid, OR 2 months of rifampin plus pyrazinamide 1
- Alternative: 4 months of rifampin alone 1
- For children: 9 months of isoniazid only 1