Category Archives: Evidence Informed Healthcare

WHO issues updated guidance for treatment of drug-resistant tuberculosis (2 May 2022)

The World Health Organization (WHO) has recently issued a rapid communication containing updated guidance for the treatment of drug-resistant tuberculosis.

The rapid communication is intended to allow rapid transition and implementation of the new guidelines by National Tuberculosis Programmes (NTPs) in advance of detailed guidance that will be released later this year.

Background Information:

Multidrug-resistant tuberculosis (MDR-TB): combined resistance to rifampicin and isoniazid, the two most important anti-TB medicines.

Rifampicin-resistant tuberculosis (RR-TB): resistance to rifampicin.

pre-XDR-TB: TB caused by Mycobacterium tuberculosis strains that fulfil the definition of MDR/RR-TB and are also resistant to any fluoroquinolone.

XDR-TB: TB caused by M. tuberculosis strains that fulfil the definition of MDR/RR-TB and which are also resistant to any fluoroquinolone and at least one additional Group A drug.

Extensive (or advanced) pulmonary TB disease: the presence of bilateral cavitary disease or extensive parenchymal damage on chest radiography. In children aged under 15 years, advanced disease is usually defined by the presence of cavities or bilateral disease on chest radiography.

Severe extrapulmonary TB: the presence of miliary TB or TB meningitis. In children aged under 15 years, extrapulmonary forms of disease other than lymphadenopathy (peripheral nodes or isolated mediastinal mass without compression) are considered as severe.

Pretomanid: a new chemical entity and a member of a class of compounds known as nitroimidazooxazines. It was developed by the TB Alliance as an oral tablet formulation for the treatment of TB in combination with other anti-TB agents.

TB-PRACTECAL: a clinical trial to test a novel shorter, all-oral treatment regimen for MDR/RR-TB or pre-XDRTB.

ZeNix: a study to further test the BPaL regimen (the Nix-TB regimen) with lower exposure of linezolid that holds the potential to be a safer option. The Nix-TB
regimen comprises pretomanid, bedaquiline and linezolid for 6–9 months.

6-month BPaLM regimen: comprises of bedaquiline, pretomanid, linezolid (600 mg) and moxifloxacin.

NeXT study: a clinical trial conducted in South Africa to test a novel regimen – 6-9 Bdq-Lzd-Lfx-ZEto/Hh/Trd – for treatment of MDR/RR-TB without fluoroquinolone resistance.

Key Messages:

Tuberculosis (TB) remains a threat to global public health and is one of the leading infectious causes of death globally.

In 2020, an estimated 10 million people developed TB and 1.5 million died from the disease.

Owing to the impact of the coronavirus disease (COVID-19) pandemic, TB incidence could increase globally in 2022 and 2023.

About 500 000 new cases of multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB) are estimated to emerge each year; however, in the latest data (from 2019), only one in three cases were reported to have been treated.

In recent years, significant progress in the availability of improved diagnostics and more effective medicines has led to earlier detection and higher treatment success rates among patients with MDR/RR-TB in several countries.

All patients with MDR/RR-TB, including those with additional resistance to fluoroquinolones, stand to benefit from effective all-oral treatment regimens, either shorter or longer, implemented under programmatic conditions.

  • The 6-month BPaLM regimen, comprising bedaquiline, pretomanid, linezolid (600 mg) and moxifloxacin, may be used programmatically in place of 9-month or longer (>18 months) regimens, in patients (aged ≥15 years) with MDR/RR-TB who have not had previous exposure to bedaquiline, pretomanid and linezolid (defined as >1 month exposure). This regimen may be used without moxifloxacin (BPaL) in the case of documented resistance to fluoroquinolones (in patients with pre-XDR-TB). Drug susceptibility testing (DST) to fluoroquinolones is strongly encouraged, but DST should not delay treatment initiation.
  • The 9-month, all-oral, bedaquiline-containing regimens are preferred over the longer (>18 months) regimen in adults and children with MDR/RR-TB, without previous exposure to second-line treatment (including bedaquiline), without fluoroquinolone resistance and with no extensive pulmonary TB disease or severe extrapulmonary TB. In these regimens, 2 months of linezolid (600 mg) can be used as an alternative to 4 months of ethionamide. Access to rapid DST for ruling out fluoroquinolone resistance is required before starting a patient on one of these regimens.
  • Patients with extensive forms of DR-TB (e.g. XDR-TB) or those who are not eligible for or have failed shorter treatment regimens will benefit from an individualized longer regimen designed using the priority grouping of medicines recommended in current WHO guidelines.
  • Decisions on appropriate regimens should be made according to clinical judgement and patient preference, considering results of DST, patient treatment history, risk of adverse events, and severity and site of the disease.

The WHO will issue consolidated guidelines for the treatment of drug-resistant tuberculosis later in 2022, that will replace all previous guidance.

Useful Links:

Link to the related WHO news release:

Link to the rapid communication issued by WHO: