WHO treatment guidelines for multidrug- and rifampicin-resistant tuberculosis, 2018 update
Tuberculosis (TB) strains with multidrug- and rifampicin-resistance (MDR/RR-TB) are more difficult to treat than drug-susceptible TB and threaten global progress towards the targets of the End TB Strategy set by the World Health Organization (WHO). The WHO treatment guidelines for multidrug- and rifampicin-resistant tuberculosis, 2018 update addresses the mandate of WHO to inform health professionals in Member States on how to improve MDR/RR-TB care.
In 2018, WHO convened a Guideline Development Group (GDG) to update its policy recommendations on the treatment of MDR/RR-TB. The GDG was composed of a multidisciplinary group of external experts with experience in different aspects of the programmatic management of MDR/RR-TB as well as affected individuals. Ahead of their meeting in July 2018 in Switzerland, the GDG defined seven priority questions for the updated guidelines to cover. Topical areas of uncertainty on the composition and duration of longer MDR-TB regimens for adults and children, on when the standardized 9-12 month shorter MDR-TB regimen may be offered and the use of culture to monitor treatment response were included in the scope. Other aspects of MDR/RR-TB care for which no new evidence has emerged since the last time WHO policy was revised, such as the timing of antiretroviral therapy in MDR/RR-TB patients with human immunodeficiency virus (PLHIV), use of surgery and different models of care, were not reviewed and previous policies thus remain valid.
The new recommendations, based on the most recent available evidence, signal an important departure from previous approaches to treat MDR/RR-TB. Injectable agents are no longer among the priority medicines when designing longer MDR-TB regimens, with kanamycin and capreomycin not recommended any more. Fully oral regimens should thus become the preferred option for most patients. Three medicines – fluoroquinolones (levofloxacin or moxifloxacin), bedaquiline and linezolid – are strongly recommended to use in a longer regimen, which is completed with other medicines ranked by a relative balance of benefits to harms. Most regimens would include at least four agents likely to be effective in the first 6 months and three thereafter. The proposed total duration of longer MDR-TB regimens is about 18-20 months, modified depending upon patient response. The standardised, shorter MDR-TB regimen may be offered to eligible patients who agree to a briefer treatment (9-12 months) that may be less effective than an individualized longer regimen and that requires a daily injectable agent for at least four months. Monitoring MDR-TB regimens with monthly culture rather than sputum microscopy alone offers the best option to detect a failing regimen in time for corrective action.