Standard tuberculosis treatment regimen and its duration

What it is

Treatment of tuberculosis has four goals: eradication of Mycobacterium tuberculosis infection, preventing transmission, preventing relapse of disease, and preventing development of drug resistance.

The 6 months of standard treatment are the end of a long history. Streptomycin efficacy was shown in 1946, isoniazid in 1952 made TB curable, and rifampin followed in 1970. In the INH era treatment ran for 2 years; INH with RMP reduced it to 9 months; and INH with RMP, PZA and ethambutol reduced it to the 6 months used now.

How it is treated

Standard treatment involves 6 months' therapy for all patients with new-onset pulmonary TB and non-CNS extrapulmonary TB, in two phases. The initial intensive phase is designed to kill actively growing bacteria: isoniazid, rifampin, pyrazinamide and ethambutol for 2 months. The continuation phase then destroys any remaining bacteria: isoniazid and rifampin for the next 4 months. This is written as 2 months of HRZE followed by 4 months of HR, where H is isoniazid, R is rifampicin, Z is pyrazinamide and E is ethambutol.

• 2 months of HRZE followed by 4 months of HRE applies only in countries with high levels of isoniazid resistance in new TB patients, or where isoniazid drug susceptibility testing in new patients is not done before the continuation phase begins.
• Daily dosing in both phases is optimal. Daily then 3 times/wk is an acceptable alternative for any new patient receiving directly observed therapy. 3 times/wk in both phases is acceptable only with directly observed therapy and only in a patient not living with HIV and not living in an HIV-prevalent setting. Daily rather than 3 times weekly intensive-phase dosing may help prevent acquired drug resistance in TB patients starting treatment with isoniazid resistance.
• Doses: isoniazid 200 to 300 mg/day (5 mg/kg/day); rifampicin 450 to 600 mg/day (10 mg/kg/day); pyrazinamide 20 to 30 mg/kg/day; ethambutol 10 to 25 mg/kg/day; streptomycin 1 gm I.M daily.
• If drug sensitivity is unavailable at 2 months, continue the 4 drug regime until it is available. Pyrazinamide may be discontinued after it has been taken for 2 months (56 doses), and ethambutol may be discontinued when results of drug susceptibility testing indicate no drug resistance. Therapy should be extended to 9 months if the 2 month culture is positive.

The choice and duration of antituberculous therapy for extrapulmonary TB is the same as for pulmonary TB, with two exceptions: central nervous system disease takes 12 months, and bone and joint disease 6 to 9 months. CNS TB is written as 12 months of 2HRZE + 10HR, and ethambutol may be replaced by streptomycin, plus prednisolone 20-40 mg o.d. weaning over 2-4 weeks. Adjunctive corticosteroids are warranted in tuberculous meningitis and constrictive pericarditis, and are also recommended for pericardial effusion, pleural effusion and TB of the ureter, in children with endobronchial disease, and to suppress hypersensitivity drug reactions. Latent TB takes 3 months of 3RH or 6 months of 6H.

Most patients can be treated at home. Admission to a hospital unit with appropriate isolation should be considered for uncertainty about the diagnosis, intolerance of medication, adverse social conditions, or significant risk of MDR-TB. Where drug resistance is not anticipated, patients can be assumed to be non-infectious after 2 weeks of appropriate therapy.