Drug-resistant tuberculosis treatment

Longer versus shorter regimens. The conditionality of the recommendation for the use of the 
shorter MDR-TB regimen may require the patient and health care provider to decide on longer 
treatment in patients who are otherwise eligible for the shorter MDR-TB regimen, based on the 
individual circumstances. Such circumstances include uncertainty about DST results or lack of access 
to second-line LPA, unavailability of clofazimine or another component medicine, or the patient’s 
condition requiring immediate start of treatment before all baseline testing can be completed. If the 
shorter MDR-TB regimen cannot be used, the patient needs to be reassessed with a view to starting 
a longer MDR-TB treatment regimen. Usually, a patient started on the shorter MDR-TB regimen can 
later be transferred to a longer regimen should the need arise. However, in general, patients who are 
placed on a longer regimen for at least 4 weeks can no longer be switched to the shorter
regimen.
Dosage and duration. The guidelines update in 2018 concurrently revised the weight-based dosage 
schedules for medicines used in MDR-TB regimens for both children and adults (see the Operational 
handbook on tuberculosis). The update to the dosages benefited from the expertise of the GDG 
members, and from an extensive consultation with other specialists in different fields. It was based on 
the latest knowledge available about the optimal use of the medicines involved (84). Adherence to the 
schedules is advised as far as possible. Manipulation of tablets (e.g. splitting, crushing or dissolving 
in water) outside their indications is to be avoided because this may interfere with the bioavailability 
of the drugs.
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In patients taking amikacin or streptomycin who are culture positive at the start of treatment, all three 
recommendations on the duration of treatment apply. For patients on an all-oral MDR-TB regimen, 
the length of treatment is determined by the recommendations on total duration and time after 
culture conversion (Recommendations 3.15 and 3.16, respectively). In patients with bacteriologically 
negative TB or most forms of extrapulmonary disease, Recommendation 3.15 on total duration is 
the only applicable
recommendation.
The 6-month duration of use of bedaquiline and delamanid generally recommended in these 
guidelines reflects how these medicines have been used in most of the patient data reviewed, which 
is aligned to the prescribing recommendations that their manufacturers filed with regulatory authorities 
(e.g. (85–87). New evidence on the safety profile of bedaquiline use beyond 6 months suggests that 
it is safe in patients who receive appropriate baseline and follow-up monitoring. However, in contrast 
to bedaquiline and delamanid, several of the other medicines included in MDR-TB regimens (e.g. 
fluoroquinolones and clofazimine) are used outside their licensed indication, and the recommended 
duration of use in MDR-TB regimens is often much longer than the one proposed for their original 
licensed purpose. Other medicines may need to be used for shorter durations because of toxicity 
associated with their long-term administration (particularly
linezolid).
It is important to prevent treatment interruption, to increase the likelihood of treatment success. 
Measures that can help to increase retention include supporting patient adherence, either by 
facilitating patient visits to health care facilities or home visits by health care staff, or by using digital 
technologies for daily communication (29).