What is the standard treatment regimen for drug‑susceptible (non‑multidrug‑resistant) tuberculosis, including drug selection, dosing, duration, and monitoring?

Standard Treatment Regimen for Drug-Susceptible Tuberculosis

The recommended treatment for newly diagnosed drug-susceptible tuberculosis is a 6-month regimen consisting of an intensive phase of 2 months with four drugs (isoniazid, rifampin, pyrazinamide, ethambutol) given daily, followed by a continuation phase of 4 months with two drugs (isoniazid, rifampin) given daily. 1, 2

Intensive Phase (First 2 Months)

Drug Selection and Dosing:

• Isoniazid 5 mg/kg (typically 300 mg) daily 1, 2
• Rifampin 10 mg/kg (typically 600 mg for patients ≥50 kg, 450 mg for <50 kg) daily 1, 2
• Pyrazinamide 25 mg/kg (20-30 mg/kg range) daily 1
• Ethambutol 15 mg/kg daily 1, 2

Duration: 56 doses over 8 weeks 1

Why Four Drugs? The four-drug approach is required because a substantial proportion of new tuberculosis cases worldwide are caused by organisms resistant to isoniazid. 1 Ethambutol may be discontinued once drug susceptibility results confirm full susceptibility to both isoniazid and rifampin, or if the community has documented primary isoniazid resistance <4% and the patient has no prior treatment history or exposure to resistant cases. 1, 2

Continuation Phase (Months 3-6)

Drug Selection and Dosing:

• Isoniazid 5 mg/kg (typically 300 mg) daily 1, 2
• Rifampin 10 mg/kg (typically 600 mg) daily 1, 2

Duration: 126 doses over 18 weeks (4 months) 1, 2

When to Extend to 9 Months Total: Patients with both cavitary disease on initial chest radiograph and positive sputum culture at completion of 2 months of treatment should receive an extended continuation phase of 7 months (total 9 months of therapy). 1, 2

Administration Schedule

Daily dosing is strongly preferred for both intensive and continuation phases. 1, 2

Directly Observed Therapy (DOT):

• DOT should be used for all tuberculosis patients to ensure treatment completion and prevent emergence of drug resistance. 1, 2
• When DOT is employed, a 5-days-per-week schedule is an acceptable alternative to 7-days-per-week administration based on extensive clinical experience. 1, 2

Pyridoxine (Vitamin B6) Supplementation

Mandatory supplementation with pyridoxine 25-50 mg daily for all individuals at risk of peripheral neuropathy: 1, 2

• Pregnant women
• Breastfeeding infants
• HIV-infected persons
• Patients with diabetes mellitus
• Patients with alcoholism
• Patients with malnutrition
• Patients with chronic renal failure
• Older adults

If peripheral neuropathy develops, increase pyridoxine dose to 100 mg daily. 1, 2

Monitoring During Treatment

Baseline Assessment:

• Obtain sputum smear and culture with drug susceptibility testing for isoniazid, rifampin, ethambutol, and pyrazinamide before starting treatment. 2
• Perform baseline hepatic function tests (AST/ALT and bilirubin) in high-risk patients: HIV-infected, pregnant women, those with chronic liver disease history, and regular alcohol users. 2

Follow-up Monitoring:

• Obtain sputum smear and culture at completion of the 2-month intensive phase and at treatment completion. 2
• Monitor monthly for weight, adherence, symptom improvement, and adverse effects. 2

Special Populations

HIV-Infected Patients on Antiretroviral Therapy:

• Use the same standard 6-month daily regimen (2 months HRZE / 4 months HR). 1, 2
• Never use intermittent (twice- or thrice-weekly) regimens in HIV-infected patients due to high rates of relapse and acquired drug resistance. 1, 2

HIV-Infected Patients NOT on Antiretroviral Therapy:

• Extend the continuation phase by an additional 3 months (total 9 months of therapy: 2 months HRZE / 7 months HR). 1, 2

Critical Pitfalls to Avoid

Do NOT omit ethambutol from the initial four-drug regimen unless drug susceptibility results are already available confirming full susceptibility to isoniazid and rifampin, or the community has documented primary isoniazid resistance <4% in patients without prior treatment or exposure to resistant cases. 2

Do NOT use twice-weekly dosing in HIV-infected patients or those with smear-positive or cavitary disease, as missed doses effectively become once-weekly therapy, which markedly increases risk of treatment failure and relapse. 1, 2

Do NOT use intermittent (thrice-weekly) regimens except in carefully selected HIV-negative patients with non-cavitary, smear-negative disease after an initial 2-week daily period, and only with strict DOT. 2 Even then, daily dosing remains strongly preferred. 1, 2

Avoid hepatotoxicity: Monitor liver function tests twice weekly during the first 2 weeks, every 2 weeks during the remainder of the first 2 months, then monthly. 3 If transaminases rise to >3 times the upper limit of normal, stop isoniazid, rifampin, and pyrazinamide. 3