Tuberculosis: Multidrug-resistant (MDR-TB) or rifampicin-resistant TB (RR-TB)

MDR/RR-TB definition usually refers to either multidrug-resistant TB (MDR-TB) or rifampicin-resistant TB (RR-TB).

Multidrug-resistant TB (MDR-TB) is a form of TB disease caused by a strain of M. tuberculosis complex that is resistant to rifampicin and isoniazid.

Globally, an estimated 370 000 people (95% UI: 330 000–400 000) developed rifampicin-resistant tuberculosis (RR-TB) in 2025. The treatment success rate for people diagnosed with RR-TB has improved substantially, but it remains much lower than for drug-susceptible TB (about 90%). Globally, among people enrolled on treatment in 2023 (the latest year for which outcome data are available), the treatment success rate was 70%, compared with 71% in 2022, 68% in 2021. The two reasons why MDR/RR-TB continues to emerge and spread are mismanagement of TB treatment and person-to-person transmission. Most people with TB are cured by a 6-month treatment regimen that is provided to patients with adequate support. Inappropriate or incorrect use of TB drugs, use of ineffective formulations of drugs (such as the use of single drugs, poor quality medicines or bad storage conditions), and premature treatment interruption can cause drug resistance, which can then be transmitted, especially in crowded settings such as prisons and hospitals. Patients with TB of the lungs can spread the disease by coughing, sneezing or simply talking. To become infected, a person needs only to breathe in a small number of these germs.

Based on current WHO policy, several regimens can be used in patients with MDR/RR-TB. The key factors that define treatment regimen choice include the patient's drug-resistance profile, prior exposure to TB medicines and patient history, the drug-resistance profile of close contacts, the patient’s age, the extent of pulmonary TB disease, and the localization of extrapulmonary TB lesions.

• The 6-month BPaL/M/C regimen (6 Bdq-Pa-Lzd-Mfx/Cfz) – comprising bedaquiline, pretomanid, linezolid and moxifloxacin or clofazimine – is a preferred regimen for adults and adolescents aged 14 years and older and is recommended for patients with MDR/RR-TB or pre-extensively drug-resistant TB (pre-XDR-TB). Patients with unknown FQ resistance can be initiated on the BPaLM regimen while waiting for DST results. In cases where resistance to FQ (pre-XDR-TB) is identified before or after initiation of treatment, the BPaL or BPaLC regimen can be initiated or continued, depending on disease severity (BPaL for non-severe and BPaLC for severe pulmonary pre-XDR-TB).
• The 6-month BDLLfx/C regimen (6 Bdq-Dlm-Lzd-Lfx-Cfz) – comprising bedaquiline, delamanid, linezolid, levofloxacin and clofazimine – is an alternative regimen for individuals with MDR/RR-TB or pre-XDR-TB and may be used for children, adolescents below 14 years of age and pregnant or breastfeeding women. Depending on the availability of FQ DST results, the regimen may be used with or without levofloxacin or clofazimine. In cases of unknown FQ resistance, BDLLfxC can be initiated without delay; BDLLfx is used for FQ-susceptible TB, and BDLC (bedaquiline, delamanid, linezolid and clofazimine) for non-severe forms of pre-XDR-TB. Patients with severe forms of pre-XDR-TB may need to receive BPaLC or, if younger than 14 years of age, the longer individualized regimen.

In patients with MDR/RR-TB and in whom resistance to FQ has been excluded, modified 9-month regimens (BLMZ, BLLfxCZ and BDLLfxZ) are available and are generally preferred over the other 9-month regimens or longer (18-month) regimens.

• BLMZ is the first choice among the recommended modified 9-month regimens. In terms of the balance of health effects it is preferable to both BLLfxCZ and BDLLfxZ. Also, at the time of the review, it had a lower pill burden, fewer AEs, balanced efficacy and cost and appeared either preferable or equivalent for all other decision criteria. It comprises bedaquiline, linezolid, moxifloxacin and pyrazinamide.
• BLLfxCZ is the second option if BLMZ is unsuitable. BLLfxCZ, compared to BDLLfxZ has a similar but slightly preferable balance of health effects, significantly lower cost and a lower pill burden than BDLLfxZ. It comprises bedaquiline, linezolid, levofloxacin, clofazimine and pyrazinamide.
• BDLLfxZ is the third option for patients who cannot use BLMZ or BLLfxCZ. It comprises bedaquiline, delamanid, linezolid, levofloxacin and pyrazinamide. Although delamanid has a favourable safety profile, its current high price and limited Phase 3 trial data make this regimen less favourable.

If none of the above regimens can be used, an alternative option is the seven-drug-containing 9-month regimen, which offers variations incorporating ethionamide or linezolid.

• 9-month regimen (4–6 Bdq_{(6 m)}-Lfx/Mfx-Cfz-Z-E-Hh-Eto or Lzd_{(2 m)} / 5 Lfx/Mfx- Cfz-Z-E): in patients with MDR/RR-TB and in whom resistance to fluoroquinolones has been excluded. The 9-month all-oral regimen comprises bedaquiline (used for six months), in combination with levofloxacin/moxifloxacin, ethionamide, ethambutol, isoniazid (high dose), pyrazinamide and clofazimine (for four months, with the possibility of extending to 6 months if the patient remains sputum smear positive at the end of 4 months); followed by treatment with levofloxacin/moxifloxacin, clofazimine, ethambutol and pyrazinamide (for five months). Ethionamide can be replaced by two months of linezolid.
• Longer individualized regimens: for patients with MDR/RR-TB who are not eligible for, or had no favourable treatment outcome using, the above 6-month or 9-month regimens, have TB disease caused by M. tuberculosis strains with extensive drug resistance (e.g. extensively drug-resistant TB [XDR-TB]) or have intolerance to key components of the above-mentioned shorter regimens. These regimens have a duration of at least 18 months and are individually designed based on a hierarchical grouping of second-line TB medicines, the drug-resistance profile and the patient’s medical history.

Based on the review of the latest available evidence, the 6-month BPaLM regimen is the preferred option for most patients with MDR/RR-TB.