What is the recommended treatment for active tuberculosis (TB)?

Treatment of Active Tuberculosis

For most adults with previously untreated, drug-susceptible active tuberculosis, initiate a 2-month intensive phase with isoniazid, rifampin, pyrazinamide, and ethambutol, followed by a 4-month continuation phase with isoniazid and rifampin. 1

Initial Phase (First 2 Months)

The standard four-drug regimen consists of: 1, 2, 3, 4

• Isoniazid (INH)
• Rifampin (RIF)
• Pyrazinamide (PZA)
• Ethambutol (EMB)

Ethambutol may be omitted only if drug susceptibility testing confirms the organism is susceptible to isoniazid, rifampin, and pyrazinamide. 1 However, in geographic areas where ≥4% of TB isolates are resistant to isoniazid, all four drugs must be used initially. 1

Dosing Options for Initial Phase

The intensive phase can be administered using three different schedules: 1

• Daily dosing (7 days/week)
• Daily for 2 weeks, then twice weekly for 6 weeks (requires directly observed therapy [DOT])
• Three times weekly throughout (requires DOT)

When to Initiate Treatment

Begin treatment immediately in patients who are seriously ill with suspected TB, even before culture results are available. 1 The decision should be based on: 1

• Clinical presentation and symptoms
• Radiographic findings on chest X-ray
• Positive acid-fast bacilli (AFB) smear results
• Epidemiologic risk factors

A positive AFB smear provides strong evidence for TB diagnosis and warrants immediate four-drug therapy. 1

Continuation Phase (Months 3-6 or Longer)

Standard 4-Month Continuation Phase

For the majority of patients, continue isoniazid and rifampin for 4 additional months (total treatment duration: 6 months). 1

This can be given: 1

• Daily (7 days/week)
• Twice weekly by DOT
• Three times weekly by DOT

Extended 7-Month Continuation Phase (Total 9 Months)

A 7-month continuation phase is required for: 1

• Patients with cavitary pulmonary TB on initial chest radiograph AND positive sputum culture at completion of 2 months of treatment
• Patients whose initial phase did not include pyrazinamide
• Patients receiving once-weekly isoniazid and rifapentine who had positive sputum culture at 2 months

HIV-Infected Patients

For HIV-infected patients with CD4 count <100 cells/µL, the continuation phase must be given daily or three times weekly (not twice weekly). 1 Consider extending treatment duration, as HIV-infected patients may require longer courses. 2

Critical Monitoring Points

At 2 Months

Obtain repeat sputum smear and culture at completion of the initial 2-month phase. 1 This determines:

• Whether the standard 4-month continuation is sufficient
• Whether extension to 7 months is needed (if cavitary disease present and culture still positive)

At 3 Months

Reevaluate all patients who remain smear-positive at 3 months for possible nonadherence or drug-resistant TB. 1 Perform repeat culture and susceptibility testing within 1 month. 1

Drug-Resistant Tuberculosis

Isoniazid Resistance Only

Use rifampin, pyrazinamide, and ethambutol for 6-9 months or 4 months after culture conversion. 1 Intermittent twice-weekly therapy can be used after at least 2 weeks of daily therapy. 1

Rifampin Resistance Only

Use a 9-month regimen with isoniazid, streptomycin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid, streptomycin, and pyrazinamide for 7 months. 1

Multidrug-Resistant TB (MDR-TB: Resistant to Both Isoniazid and Rifampin)

Consult immediately with a TB expert experienced in MDR-TB management. 1 For patients meeting specific criteria (no prior second-line drug exposure >1 month, no fluoroquinolone resistance, not extensively diseased, not pregnant, age >6 years), consider the shorter 6-month all-oral bedaquiline-containing regimen. 1

The shorter MDR-TB regimen includes: 1

• Intensive phase (4-6 months): Bedaquiline, levofloxacin/moxifloxacin, clofazimine, pyrazinamide, ethambutol, high-dose isoniazid, ethionamide
• Continuation phase (5 months): Levofloxacin/moxifloxacin, clofazimine, pyrazinamide, ethambutol

For extensively drug-resistant cases or those not meeting criteria for the shorter regimen, individualized longer regimens using prioritized drug groups are necessary. 1 Most MDR-TB regimens include an aminoglycoside and a fluoroquinolone, with treatment lasting 24 months after culture conversion. 1

Common Pitfalls to Avoid

Never add a single drug to a failing regimen - this creates functional monotherapy and rapidly selects for additional drug resistance. 1 Always add at least 2 new drugs to which the organism is susceptible. 1

Do not use twice-weekly dosing in HIV-infected patients with CD4 <100 cells/µL - treatment failure rates are unacceptably high. 1

Do not stop ethambutol prematurely in areas with ≥4% isoniazid resistance - wait for susceptibility results before discontinuing the fourth drug. 1

Report all TB cases to local public health authorities within 1 week of diagnosis - this is mandatory for contact tracing and surveillance. 1