Drug-resistant tuberculosis treatment

Patients with extensive TB disease. The duration of treatment post culture conversion may be 
modified according to the patient’s response to therapy (e.g. culture conversion before 2 months of 
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Low birth weight was defined as less than 2500 g. 

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WHO consolidated 
guidelines 
on
tuberculosis: 
drug-resistant tuberculosis treatment
37
treatment) and other risk factors for treatment failure or relapse. This should be considered in patients 
with extensive TB
disease.
Patients on regimens without amikacin/streptomycin. In patients on regimens that do not contain 
injectable agents in the intensive phase, Recommendation 3.17 does not apply, and the length of 
treatment is determined by recommendations on total duration and on time after culture conversion 
(i.e. Recommendations 3.15 and 3.16). This situation is expected to apply to an increasing proportion 
of patients in future who are treated with oral-only regimens. If bedaquiline or other agents (e.g. 
linezolid or delamanid) are given only for the initial part of a regimen, this period does not equate 
to an “intensive phase” unless an injectable agent is used concurrently, as premised by the meta-
analysis that informed Recommendation 3.17.
3.5 Implementation considerations
The new recommendations signal an important departure from previous approaches to treating MDR/
RR-TB. The implementation of MDR-TB treatment on a large scale is feasible under programmatic 
conditions, as has been shown by the global expansion in the use of standardized and individualized 
MDR-TB regimens in low-, middle- and high-income countries worldwide, particularly in the past 
decade (1). The 2018 revision of the guidelines brought important changes to the grouping of 
medicines, the composition of longer MDR-TB regimens and the duration of medicine use, but it 
is expected that implementation of these changes will be feasible. The rapidity with which the new 
recommendations are applied in (or to) programmes may be influenced by a range of factors, but 
these should not stand in the way of increased access to life-saving treatment for patients who need
it.
All of the agents recommended for use are available via the GDF, and most are also available in 
quality-assured, affordable generic formulations from other sources. Bedaquiline was available via 
a donation programme until March 2019; it is now available via the GDF, and a decrease in price 
has been negotiated with the manufacturer for low-resource settings. The evidence assessed during 
the GDG meeting in November 2019 did not allow the group to make any judgements about the 
efficacy or effectiveness of bedaquiline when used for longer than 6 months; however, it did allow the 
GDG to determine that the safety profile of bedaquiline use for longer than 6 months is becoming 
clearer. The group concluded that bedaquiline can be safely used in patients beyond 6 months, if 
decided by the programme or treating clinician, and if appropriate schedules of baseline testing 
and monitoring are in place. In addition, the treating clinician should be aware of the use of other 
potentially QT-prolonging medications in any MDR/RR-TB regimen, and the comparatively long half-
life of bedaquiline, which means that bedaquiline will remain in human tissue beyond the duration 
of its use. The half-life of bedaquiline is about 6 months, and the half-life of the N-monodesmethyl 
metabolite (M2) is about 5.5 months (82).
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