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Treatment of Multidrug-Resistant Tuberculosis: The latest guidance from WHO

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Treatment of multidrug-resistant and rifampicin-resistant tuberculosis (MDR/RR-TB) is difficult. The average proportion of MDR/RR-TB with a successful treatment was less than 60% globally in past 15 years.

A 9-month regimen piloted in Bangladesh comprised high-dose gatifloxacin, clofazimine, ethambutol and pyrazinamide throughout, supplemented by kanamycin, protionamide and high-dose isoniazid during an intensive phase heralded the era of short course chemotherapy for the treatment of MDR/RR-TB.

This so-called Bangladesh regimen achieved a high treatment success proportion in several settings and has been shown to be non-inferior to the long regimens recommended by the World Health Organization (WHO) in the STREAM clinical trial (N Engl J Med 2019;380:1201-1213).

Dr Chen-Yuan Chiang, Senior Consultant at The Union

Dr Chen-Yuan Chiang, Senior Consultant at The Union


What has changed?  

Recently, WHO issued rapid communication recommending that:

“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. Drug susceptibility testing (DST) to fluoroquinolones is strongly encouraged, but DST should not delay treatment initiation.”

This is a welcome development, but long-term follow-up data of patients treated with these regimens are crucial. WHO further recommended that:

“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.

Access to rapid DST for ruling out fluoroquinolone resistance is required before starting a patient on one of these regimens.”

The challenge we face is that ensuring rapid drug susceptibility testing of fluoroquinolone is difficult in low- and middle-income countries. The use of WHO-recommended 9-month, all-oral, bedaquiline-containing regimens in the treatment of MDR-/RR-TB patients with undetected resistance to fluoroquinolones runs a high risk of acquired bedaquiline resistance, especially in settings with a high prevalence of fluoroquinolone resistance.

Stay up to date

These challenges will be addressed in the upcoming international course of The Union on the Clinical Management of Drug-Resistant TB. Dr Chen-Yuan Chiang is the Course Director.

The course is taking place online in October 2022. Participants who register and pay the fee for the course 3 months before it begins will receive a 5% discount.

Find out more and register for the course by clicking on the orange button below.