What is the recommended treatment regimen for drug-susceptible tuberculosis using antitubercular (anti-tuberculosis) drugs?

Treatment of Drug-Susceptible Tuberculosis

For drug-susceptible tuberculosis, treat with a 6-month regimen consisting of 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol (intensive phase) followed by 4 months of isoniazid and rifampin (continuation phase), administered daily with directly observed therapy. 1

Standard Treatment Regimen

Intensive Phase (First 2 Months)

• Four-drug regimen: Isoniazid (INH), Rifampin (RIF), Pyrazinamide (PZA), and Ethambutol (EMB) 1, 2
• Adult dosing:
  • Isoniazid: 5 mg/kg (typically 300 mg) daily 1, 3
  • Rifampin: 10 mg/kg (typically 600 mg) daily 1
  • Pyrazinamide: 35 mg/kg daily for patients <50 kg or 2.0 g daily for patients >50 kg 2
  • Ethambutol: 15 mg/kg daily 2, 4
• Pediatric dosing:
  • Isoniazid: 10-15 mg/kg daily 1, 3
  • Rifampin: 10-20 mg/kg daily 1
  • Pyrazinamide and Ethambutol: weight-based dosing 1

Continuation Phase (Next 4 Months)

• Two-drug regimen: Isoniazid and Rifampin only 1, 2
• Same daily dosing as intensive phase for both drugs 1
• Complete all doses within 6 months from continuation phase start 5

Critical Modifications Based on Drug Susceptibility

• Ethambutol can be discontinued immediately once drug susceptibility testing confirms the isolate is susceptible to both isoniazid and rifampin 1, 2
• If susceptibility is known before treatment initiation and the organism is susceptible to both INH and RIF, the intensive phase can consist of only INH, RIF, and PZA (ethambutol is unnecessary) 1
• The four-drug intensive phase is used because of the current global proportion of isoniazid-resistant TB cases 1

Dosing Frequency and Administration

• Daily dosing throughout both phases is the preferred frequency 1, 5
• Five-days-a-week administration by directly observed therapy (DOT) is an acceptable alternative to 7-days-a-week administration based on substantial clinical experience 1
• Thrice-weekly dosing in the continuation phase is acceptable but requires higher doses (INH 15 mg/kg up to 900 mg, RIF 10 mg/kg up to 600 mg) 1, 5
• Twice-weekly dosing is not recommended 5
• Once-weekly therapy with INH and rifapentine in the continuation phase is not recommended 5

Essential Adjunctive Therapy

• Pyridoxine (vitamin B6) 25-50 mg daily must be given with isoniazid to all persons at risk of neuropathy 1, 2
• High-risk groups requiring pyridoxine include:
  • Pregnant women 1, 2
  • Breastfeeding infants 1, 2
  • HIV-positive patients 1, 2
  • Patients with diabetes, alcoholism, malnutrition, or chronic renal failure 1, 2
  • Patients of advanced age 1
• For patients who develop peripheral neuropathy, increase pyridoxine to 100 mg daily 1

Directly Observed Therapy (DOT)

• DOT is strongly recommended for all TB patients to ensure treatment completion and prevent drug resistance 2, 5, 3
• Patient noncompliance is a major cause of drug-resistant tuberculosis 3
• All intermittent (twice-weekly or thrice-weekly) regimens must be administered by DOT 1, 3

Treatment Monitoring Requirements

• Drug susceptibility testing must be performed on all initial isolates 2, 3, 6
• Modify the regimen appropriately once susceptibility results are available 2, 3
• Sputum cultures should be obtained monthly until conversion 5
• Regular clinical assessment for symptom improvement is necessary 5

Management of Treatment Interruptions

• If interruption is <14 days during intensive phase: Continue treatment to complete the planned total number of doses within 3 months 5
• If interruption is ≥14 days during intensive phase: Restart treatment from the beginning 5
• If interruption occurs during continuation phase with ≥80% of doses completed and initial sputum was AFB smear negative: Continue therapy until all doses are completed 5
• If interruption occurs during continuation phase with <80% of doses completed and lapse is ≥3 months: Restart therapy from the beginning 5

Special Populations

Pregnant Women

• Do not use streptomycin (causes congenital deafness) 3, 4
• Pyrazinamide is not routinely recommended in pregnancy due to inadequate teratogenicity data 3
• Initial regimen should consist of isoniazid, rifampin, and ethambutol (unless primary isoniazid resistance is unlikely) 3

Patients Over 60 Years

• Use reduced dosages due to increased risk of toxicity 4
• For streptomycin (if used): 500 mg twice daily instead of 1 g twice daily 4

HIV-Infected Patients

• May require longer treatment duration 7, 3
• Screen antimycobacterial drug levels in patients with advanced HIV disease to prevent malabsorption and emergence of multidrug-resistant TB 3
• The same 6-month regimen is generally used but response may not be as satisfactory 3

Critical Pitfalls to Avoid

• Never add a single drug to a failing regimen—this leads to acquired resistance 5
• Do not use ethambutol in children whose visual acuity cannot be monitored 3
• A total streptomycin dose should not exceed 120 g over the course of therapy unless no other therapeutic options exist 4
• Ensure the entire 6-month regimen is completed within 9 months (intensive phase within 3 months, continuation phase within 6 months) 5
• Both suspected and confirmed cases must be reported to local or state health departments 6

Site-Specific Considerations

• The standard 6-month regimen is effective for musculoskeletal TB, including thoracic and lumbar spine disease 2
• Extrapulmonary TB generally responds to the same 6-month regimen, though military TB, bone/joint TB, and tuberculous meningitis in infants and children should receive 12 months of therapy 3
• Surgery is reserved only for spinal cord compression or spinal instability in spinal TB 2