Anti-Tuberculous Treatment: Current Guidelines
Drug-Susceptible Pulmonary Tuberculosis
For treatment-naïve patients with drug-susceptible TB, use a 6-month regimen consisting of 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol (2HRZE) followed by 4 months of isoniazid and rifampin (4HR). 1, 2, 3
Intensive Phase (First 2 Months)
Ethambutol can only be discontinued if drug susceptibility testing confirms full susceptibility to both isoniazid and rifampin 1, 2
The four-drug regimen is mandatory unless primary isoniazid resistance in the community is documented to be less than 4% AND the patient has no previous TB treatment, is not from a high-prevalence drug-resistance country, and has no known exposure to drug-resistant cases 1, 7
Continuation Phase (Months 3-6)
Continue isoniazid and rifampin for 4 months after completing the intensive phase 1, 2, 3
Daily dosing is strongly recommended over intermittent therapy 1, 3
Extend continuation phase to 7 months (total 9 months) if the patient has cavitary disease on chest X-ray AND positive sputum culture at 2 months 3
Critical Management Principles
Perform drug susceptibility testing on all initial isolates before finalizing the regimen 1, 4
Use directly observed therapy (DOT) for all TB patients to ensure treatment completion and prevent drug resistance 1, 3, 4
Add pyridoxine (vitamin B6) 25-50 mg daily to all patients receiving isoniazid who are pregnant, breastfeeding, HIV-infected, diabetic, alcoholic, malnourished, or have chronic renal failure 3
Monitor sputum smear and culture at 2 months (end of intensive phase) and at treatment completion 3
Reevaluate patients who remain smear-positive at 3 months for possible nonadherence or drug resistance 1
HIV Co-Infection
Use the same 6-month regimen (2HRZE/4HR) for HIV-infected patients with drug-susceptible TB. 1, 2, 3
Be vigilant about rifampin drug interactions with antiretroviral agents, particularly protease inhibitors and NNRTIs 2
Monitor clinical and bacteriologic response closely in HIV-infected patients, as response may be suboptimal 7
Never use twice-weekly dosing if CD4 count <100 cells/μL 3
Extrapulmonary and Disseminated Tuberculosis
Standard Sites (Bone/Joint, Peripheral Lymph Nodes, Pleural)
Use the standard 6-month regimen (2HRZE/4HR) for most extrapulmonary TB. 2, 7
CNS Tuberculosis (Meningitis)
Extend total treatment duration to 12 months: 2 months of HRZE followed by 10 months of HR 2
- Add adjunctive corticosteroids (dexamethasone or prednisone 60 mg/day initially, tapering over 6-8 weeks) for stages II and III disease to prevent neurologic sequelae 1, 2, 3
Tuberculous Pericarditis
Use standard 6-month regimen plus corticosteroids to prevent constrictive pericarditis 1, 2
Miliary TB and Spinal TB with Cord Compression
Consider 12-month therapy for children with miliary or bone/joint TB 7
- Add corticosteroids for spinal TB if evidence of spinal cord compression 1
Multidrug-Resistant Tuberculosis (MDR-TB)
For MDR-TB (resistance to at least isoniazid and rifampin), use at least 5 drugs in the intensive phase and 4 drugs in the continuation phase. 1
Preferred Drug Selection
Strongly recommended drugs (include these): 1
- Later-generation fluoroquinolone (levofloxacin or moxifloxacin) - strong recommendation 1
- Bedaquiline - strong recommendation 1
Conditionally recommended drugs (add to reach 5 drugs): 1
- Linezolid 1
- Clofazimine 1
- Cycloserine 1
- Pyrazinamide (if susceptible) 1
- Ethambutol (only if other more effective drugs cannot be assembled) 1
Do NOT include: 1
- Amoxicillin-clavulanate (except when using a carbapenem) - strong recommendation against 1
- Macrolides (azithromycin, clarithromycin) - strong recommendation against 1
- Ethionamide/prothionamide (if more effective drugs available) 1
Treatment Duration for MDR-TB
- Intensive phase: 5-7 months after culture conversion 1
- Total treatment duration: 15-21 months after culture conversion 1
- For pre-XDR-TB and XDR-TB: 15-24 months after culture conversion 1
Consultation with an MDR-TB expert is mandatory for all drug-resistant cases 1, 7
Latent Tuberculosis Infection (LTBI)
For LTBI without drug intolerability or drug-drug interactions, use short-course rifamycin-based regimens (3-4 months) rather than longer isoniazid monotherapy (6-9 months). 1
Preferred Regimens for LTBI
- 3 months of isoniazid plus rifapentine (weekly) 1
- 4 months of rifampin (daily) 1
- 3 months of isoniazid plus rifampin (daily) 1
Alternative Regimen for LTBI
- 6 months of isoniazid (daily) - for those unable to take rifamycins, particularly HIV-negative persons 1
Do NOT use 2 months of rifampin plus pyrazinamide due to hepatotoxicity risk 1
Common Pitfalls to Avoid
Never use fewer than four drugs in the initial phase for drug-susceptible TB, even if local isoniazid resistance is <4%, unless all specific criteria are met 1, 2, 7
Never discontinue ethambutol before drug susceptibility results are available 1, 2
Never use intermittent (twice or thrice weekly) dosing unless directly observed therapy is guaranteed 1, 3
Never use twice-weekly dosing in HIV-infected patients with CD4 <100 cells/μL 3
Never treat MDR-TB without expert consultation and at least 5 drugs in the intensive phase 1
Always report suspected and confirmed TB cases to local or state health departments promptly 1