Bibliographic information
GuidelineKey updates to the treatment of drug-resistant tuberculosis: rapid communication, June 2024.
Year of Publication2024
Issuing InstitutionWorld Health Organization
Recommendation
New
WHO suggests the use of a 6-month treatment regimen composed of bedaquiline, delamanid, linezolid (600 mg), levofloxacin, and clofazimine (BDLLfxC) in MDR/RR-TB patients with or without fluoroquinolone resistance
Recommended in favor
Conditional
Certainty of evidence
Very low
Notes and Remarks
- 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 ≥14 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).
- The 6-month BDLLfxC regimen, composed of bedaquiline, delamanid, linezolid (600 mg), levofloxacin, and clofazimine, may be used programmatically in place of 9-month or longer (>18 months) regimens, in all patients with MDR/RR-TB who have not had previous exposure to bedaquiline, delamanid and linezolid (defined as >1 month exposure). The regimen may be used without either levofloxacin or clofazimine depending on fluoroquinolone DST results - BDLLfxC can be initiated without delay in case of unknown FQ-resistance at time of diagnosis of RR-TB (and may be continued with both levofloxacin and clofazimine if FQ-DST results cannot be obtained); BDLLfx is continued for FQ-sensitive TB; BDLC for FQ-resistant TB. The available evidence included children, adolescents, pregnant and breastfeeding women, flagging the possible use of the regimen in these population groups.
- The use of the modified 9-month, all-oral regimens (BLMZ, BLLfxCZ and BDLLfxZ) is preferred over currently recommended longer (18-month) regimens in patients with MDR/RR-TB who have not had previous exposure to bedaquiline, delamanid and linezolid (defined as >1-month exposure) and in whom resistance to fluoroquinolones has been excluded. Amongst these regimens, using BLMZ is suggested over BLLfxCZ, and BLLfxCZ is suggested over BDLLfxZ. Access to rapid DST for ruling out fluoroquinolone resistance is required before starting a patient on one of these regimens.
- The 9-month, all-oral, bedaquiline-containing regimens8 are preferred over the longer (>18 months) regimens 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 forms of 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-TB4) or those who are not eligible for or have failed shorter treatment regimens will benefit from individualized longer (≥18 months) regimens 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 DST results, treatment history, risk of adverse events, and severity and site of the disease.
- All treatment should be delivered under WHO-recommended standards, including patientcentered care and support, informed consent where necessary, principles of good clinical practice, active drug safety monitoring and management, and regular monitoring of patients and drug resistance to assess regimen effectiveness.