What is the recommended treatment regimen for a patient with drug-susceptible tuberculosis (TB)?

Treatment of Drug-Susceptible Tuberculosis

For drug-susceptible pulmonary tuberculosis in patients aged ≥12 years, use a 4-month daily regimen of rifapentine, isoniazid, moxifloxacin, and pyrazinamide for 8 weeks, followed by rifapentine, isoniazid, and moxifloxacin for 9 weeks (total 119 doses), which is as effective as the standard 6-month regimen and shortens treatment duration. 1

First-Line Treatment Options

Preferred 4-Month Regimen (Most Recent Guideline)

• Intensive phase (8 weeks): Rifapentine + isoniazid + moxifloxacin + pyrazinamide daily (56 doses) 1
• Continuation phase (9 weeks): Rifapentine + isoniazid + moxifloxacin daily (63 doses) 1
• This regimen requires documented drug susceptibility to isoniazid, rifampin (as surrogate for rifapentine), pyrazinamide, and moxifloxacin before or during treatment 1
• Treatment is complete after 119 total doses, regardless of cavitation on chest radiograph 1

Important exclusions for the 4-month regimen: Do not use in patients with resistance to isoniazid, rifamycins, fluoroquinolones, or pyrazinamide; extrapulmonary TB; pregnancy or breastfeeding; age <12 years; or inability to perform baseline drug susceptibility testing 1

Standard 6-Month Regimen (Alternative)

• Intensive phase (2 months): Isoniazid + rifampin + pyrazinamide + ethambutol daily 1, 2
• Continuation phase (4 months): Isoniazid + rifampin daily 1, 2
• Ethambutol can be discontinued once susceptibility to isoniazid and rifampin is confirmed 1, 3
• Extend continuation phase to 7 months (total 9 months) if cavitary disease on chest X-ray AND positive sputum culture at 2 months 1, 2

Drug Dosing

For 6-Month Standard Regimen (Adults):

• Isoniazid: 5 mg/kg (maximum 300 mg) daily 2, 4
• Rifampin: 10 mg/kg (maximum 600 mg) daily 2, 4
• 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

For Children:

• Isoniazid: 10-15 mg/kg (maximum 300 mg) daily 4
• Rifampin: Same as adults 1
• Pyrazinamide: Same weight-based dosing as adults 2
• Ethambutol: 15 mg/kg daily (avoid if visual acuity cannot be monitored) 1

Critical Treatment Principles

Directly Observed Therapy (DOT)

• Strongly recommend DOT for all TB patients to ensure adherence and prevent drug resistance 1, 2, 5
• DOT can be provided at clinic, patient's home, workplace, or any mutually agreeable location 1
• The 4-month regimen should always be administered by DOT 1

Initial Four-Drug Therapy

• Always start with four drugs (including ethambutol) until drug susceptibility results are available, unless community isoniazid resistance is documented <4% AND the patient has no prior TB treatment, no exposure to drug-resistant cases, and is not from a high-prevalence country 1, 6
• This protects against unrecognized isoniazid resistance 1

Pyridoxine Supplementation

• Add pyridoxine (vitamin B6) 25-50 mg daily to all patients receiving isoniazid who are at risk for neuropathy: pregnant women, breastfeeding infants, HIV-infected patients, patients with diabetes, alcoholism, malnutrition, or chronic renal failure 1, 2

Monitoring During Treatment

For 4-Month Regimen:

• Sputum culture: Baseline, then monthly until two consecutive negatives 1
• Liver function tests (ALT, AST, bilirubin, alkaline phosphatase): Baseline, weeks 4,8,12, and end of treatment 1
• Electrolytes (potassium, calcium, magnesium): Same schedule as liver tests 1
• Chest radiograph: Baseline, week 8, and end of treatment 1

For 6-Month Regimen:

• Sputum smear and culture: At 2 months (end of intensive phase) and at treatment completion 2
• Baseline liver function tests: Required for HIV-infected patients, pregnant women, those with chronic liver disease history, and regular alcohol users 2

Special Populations

HIV-Infected Patients

• Use the same 6-month regimen (2HRZE/4HR) but administer daily or three times weekly—never twice weekly if CD4 <100 cells/μL 2
• The 4-month rifapentine-moxifloxacin regimen was not studied in HIV-infected patients and is not currently recommended 1
• Monitor closely for paradoxical immune reconstitution inflammatory syndrome (IRIS) 7

Pregnant Women

• Use the standard 6-month regimen with isoniazid, rifampin, ethambutol, and pyrazinamide 1, 7
• Avoid streptomycin due to fetal ototoxicity 1, 7
• Pyrazinamide use in pregnancy has inadequate teratogenicity data but is generally considered acceptable 1
• Add pyridoxine 10-25 mg daily 1, 7

Patients with Diabetes

• Use the same regimen as non-diabetic patients 7
• Strict glucose control is mandatory 7
• Oral hypoglycemic doses may need adjustment due to rifampin interaction 7

Renal Failure

• Adjust doses of streptomycin, ethambutol, and isoniazid based on creatinine clearance 7
• In hemodialysis, give ethambutol 8 hours before dialysis 7

Common Pitfalls to Avoid

1. Never add a single drug to a failing regimen—this rapidly leads to acquired resistance 8
2. Do not use twice-weekly dosing in HIV-infected patients or those with smear-positive/cavitary disease 1
3. Do not discontinue ethambutol prematurely—wait for documented susceptibility to both isoniazid and rifampin 1, 3
4. Do not use the 4-month regimen if drug susceptibility testing cannot be performed—revert to standard 6-month regimen 1
5. Do not assume compliance—poor adherence is the major cause of drug-resistant TB 4, 5

Isoniazid-Resistant TB

If isoniazid resistance is documented but rifampin susceptibility is confirmed:

• Use rifampin + ethambutol + pyrazinamide + later-generation fluoroquinolone (levofloxacin preferred) for 6 months 1, 8
• Pyrazinamide duration can be shortened to 2 months in noncavitary, lower-burden disease 1