Summary of changes made by the 2016 updates to previous World Health Organization (WHO) policy on the treatment of drug-resistant tuberculosis (TB)

The priority questions which were covered by the May 2016 update of the WHO treatment guidelines for drug-resistant TB related to the composition of treatment regimens for multidrug- and rifampicin-resistant TB (MDR/RR-TB); the effectiveness and safety of shorter MDR-TB regimens; the role of elective surgery in MDR-TB management; the treatment of isoniazid-resistant and Mycobacterium bovis tuberculosis; and the impact of delays in starting treatment. From June 2016, the WHO also reviewed additional data on bedaquiline and delamanid.
The main changes in the 2016 recommendations are:
• A second-line treatment is recommended for all patients with rifampicin-resistant tuberculosis, regardless of whether isoniazid resistance is confirmed or not.
• A shorter MDR-TB treatment regimen is conditionally recommended for MDR/RR-TB patients under specific eligibility criteria.
• Recommendations for the treatment of children with MDR/RR-TB are based on a first-ever meta-analysis of individual-level paediatric patient data for treatment outcomes.
• Medicines used in the design of longer MDR-TB treatment regimens are now grouped differently, based upon current evidence on their effectiveness and safety. Clofazimine and linezolid are now considered more important MDR-TB regimen components, while p-aminosalicylic acid has been reclassified with agents used only as a last option. Clarithromycin and other macrolides are no longer included as medicines for the treatment of MDR/RR-TB. Delamanid may also be used in patients aged 6–17 years old.
• An evidence-informed recommendation on partial resection lung surgery is now included.
The evidence available on the treatment of isoniazid-resistant TB and on the delay to starting MDR-TB treatment could not address the guideline questions. There were very few published studies on the treatment of M. bovis and the regimens differed, precluding any attempt at formulating recommendations of clinical use.
The scope of the 2016 update of MDR-TB treatment policy did not include other aspects of the programmatic management of drug-resistant TB for which no substantive new evidence had emerged since the previous revision. The 2011 recommendations regarding the testing of TB patients for rifampicin resistance, the monitoring of treatment response, the duration of longer regimens, the delay in starting antiretroviral therapy in MDR-TB patients with HIV infection and models of care thus continue to apply until future evidence reviews show a need for revision. No change is made to the recommended use of bedaquiline from those of 2013 [20, 33].