Operational Handbooks

Older patients

The dataset evaluated for the 2022 WHO guidelines included patients with uncomplicated extrapulmonary MDR/RR-TB disease. No evidence was available to discern the impact of the 9-month all-oral regimen with either linezolid or ethionamide in patients with severe extrapulmonary TB (defined in this document as the presence of miliary TB or TB meningitis).

The 9-month all-oral MDR/RR-TB regimen was evaluated in a setting with a high HIV prevalence. In the dataset analysed for the 2022 WHO guidelines, over 70% of patients starting a shorter regimen were also living with HIV, and among those, more than 90% were receiving ART. There is no reason to believe that a 9-month all-oral regimen would perform any differently in People with HIV who initiate ART early, in accordance with WHO recommendations.

If a patient starts the 9-month all-oral MDR/RR-TB regimen but is later found to be ineligible following detection of M. tuberculosis resistance to fluoroquinolones, the patient must switch to a different regimen. Such patients might be eligible for a 6-month BPaL regimen if their prior exposure to bedaquiline and linezolid was for less than 1 month and there is no demonstrated resistance to any components of the BPaL regimen. The BPaL regimen may only be considered if the patient meets the eligibility criteria and the regimen is available and feasible in the setting.

While there have been no cost–effectiveness studies looking at the BPaLM regimen, cost–effectiveness studies for the BPaL regimen have demonstrated lower costs, should the regimen be programmatically implemented. Owing to the substantially shorter treatment duration and reduced need for hospitalization (36, 37), the implementation of a national programme using BPaL for MDR/RR-TB was estimated to cost 57–78% less than conventional longer regimens, when including all costs (e.g. investigations, drugs and hospitalization) (36).

As detailed previously, DST for fluoroquinolones is advisable before starting therapy. Where DST is unavailable, a careful history of previous exposure to TB therapy is critical. Where the treatment history suggests there may be resistance to one of the components of the regimen (i.e. exposure to bedaquiline, pretomanid or linezolid in an inadequate regimen is greater than 1 month and DST is unavailable), the BPaLM/BPaL therapy should not be commenced, and a longer individualized regimen should be considered.

Infants aged under 3 months or weighing less than 3 kg (including premature birth (under 37 weeks) were not eligible for inclusion in the SHINE trial. No new data on treatment of congenital TB and very young infants aged 0–3 months with TB disease were received following a call for data.