3. Treatment of DS-TB using the 6-month regimen

All patients with DS-TB without documented resistance to isoniazid and rifampicin may be treated using the 6-month rifampicin-containing regimen 2HRZ(E)/4HR, which comprises isoniazid, rifampicin, pyrazinamide and ethambutol, for 2 months followed by isoniazid and rifampicin for 4 months (1).

This regimen is based on the historical TB treatment studies conducted by the Medical Research Council of the United Kingdom of Great Britain and Northern Ireland (United Kingdom) in the 1980s (21), and it has been widely adopted worldwide. The regimen ensures a successful outcome in about 85% of patients globally, and has a low proportion of unfavourable outcomes and adverse events, although the success rate varies among WHO regions and is lower in People with HIV (1, 5). This regimen is estimated to have averted 66 million deaths during the 20 years from 2000 to 2020.

The core WHO recommendations included in the 2022 WHO guidelines for treatment of DS-TB are summarized below, with remarks

New patients with pulmonary TB should receive a regimen containing 6 months of rifampicin: 2HRZE/4HR. (Strong recommendation, high certainty of evidence)

Remarks

  • A: This recommendation also applies to extrapulmonary TB except TB of the central nervous system, bone or joint for which some expert groups suggest longer therapy
  • B: WHO recommends that national TB control programmes provide supervision and support for all TB patients to ensure completion of the full course of therapy
  • C: WHO recommends drug-resistance surveys (or surveillance) for monitoring the effectiveness of the treatment programme, and for designing standard regimens.

WHO recommends daily dosing as the best frequency throughout the entire course of treatment, as included in the recommendation below:

Wherever feasible, the optimal dosing frequency for new patients with pulmonary TB is daily throughout the course of therapy. (Strong recommendation, high certainty of evidence)

Daily administration reduces the rate of acquired drug-resistance by up to 3.3 times when comparing patients who received a daily regimen for the entire duration with those who received intermittent dosage (1). The effect of a patient missing one or more doses (either accidentally or due to stock-outs) is much more significant if the regimen is intermittent. The term “daily” indicates an intake of anti-TB drugs for 7 days per week. In patients with DS-TB, WHO does not recommend thrice-weekly dosing for either the intensive or the continuation phase of treatment as described in this recommendation:

In all patients with pulmonary DS-TB, the use of thrice-weekly dosing is not recommended in either the intensive or the continuation phases of therapy, and daily dosing remains the recommended dosing frequency. Conditional recommendation, very low certainty of evidence)

WHO recommends the use of FDC tablets, as included in the recommendation below:

The use of FDC tablets is recommended over separate drug formulations in the treatment of patients with DS-TB. (Conditional recommendation, low certainty of evidence)

WHO recommends not prolonging the continuation phase of treatment of the 6-month regimen in new pulmonary TB patients if a sputum smear is found to be positive at the end of the intensive phase of treatment, as included in the recommendation below:

In new pulmonary TB patients treated with the regimen containing rifampicin throughout treatment, if a positive sputum smear is found at completion of the intensive phase, the extension of the intensive phase is not recommended. (Strong recommendation, high certainty of evidence)

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