Drug-resistant tuberculosis treatment

PICO question 3 (MDR/RR-TB, 2018): In patients with MDR/RR-TB, which individual agents are 
more likely to improve outcomes when forming part of a longer regimen conforming to WHO 
guidelines?
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PICO question 4 (MDR/RR-TB, 2018): In patients with MDR/RR-TB on longer regimens composed 
in accordance with WHO guidelines, are outcomes safely improved with fewer or more than five 
effective medicines in the intensive
 
phase?
PICO question 5 (MDR/RR-TB, 2018): In patients with MDR/RR-TB on longer regimens composed 
in accordance with WHO guidelines, are outcomes safely improved with an intensive phase shorter 
or longer than 8
 
months?
PICO question 6 (MDR/RR-TB, 2018): In patients with MDR/RR-TB on longer regimens composed 
in accordance with WHO guidelines, are outcomes safely improved with a total duration shorter 
or longer than 20
 
months?
PICO question 7 (MDR/RR-TB, 2018): In patients with MDR/RR-TB on longer regimens composed 
in accordance with WHO guidelines, what is the minimum duration of treatment after culture 
conversion that is most likely to improve
 
outcomes?
The two relevant PICO questions considered by the GDG for the 2020 update were as follows: 
PICO question 8 (MDR/RR-TB, 2019): In MDR/RR-TB patients, does a treatment regimen containing 
bedaquiline for more than 6 months safely improve outcomes when compared with bedaquiline 
for up to 6 months as part of longer regimens otherwise conforming to WHO
 
guidelines?
PICO question 9 (MDR/RR-TB, 2019): In MDR/RR-TB patients, does concurrent use of bedaquiline 
and delamanid safely improve outcomes when compared with other treatment regimen options 
otherwise conforming to WHO
 
guidelines?
Recommendations for the design of longer MDR-TB regimens have been issued by WHO for a number 
of years, and have been implemented in many countries worldwide (1, 7, 10, 11). The recommendations 
in this section cover all forms of MDR/RR-TB; they include treatment of patients with strains susceptible 
to isoniazid, or with additional resistance to isoniazid (i.e. MDR-TB), or with resistance to other 
medicines from the first-line group (polyresistant), or from the second-line group. WHO recommends 
that all patients with TB – children or adults – diagnosed with strains shown to be resistant to rifampicin 
be placed on an MDR-TB treatment regimen (11). The addition of high-dose isoniazid or ethambutol 
(or both) could be considered to further strengthen the regimen. 
The likelihood of treatment success in MDR/RR-TB patients on longer regimens depends on patient-
level and strain factors (including severity of disease, resistance patterns and comorbidities), as well 
as access to health care (e.g. regimens with sufficient effective agents, medications of good quality, 
management of adverse events and patient support). Longer regimens with sufficient effective agents 
are known to increase the likelihood of cure and lower the risk of death in adults and children (61–64). 
The composition of longer regimens is governed by the selection of individual medicines considered 
to be effective, and by a need to combine sufficient medicines to maximize the likelihood of relapse-
free cure without increasing toxicity. Regimens may be of standardized (fixed) composition or may 
be individualized to the patient’s needs. Longer regimens usually last 18–20 months or more; this 
document provides recommendations on the duration of such regimens, updated since the 2011 
WHO guidelines (7). In summary, in 2018, a total treatment duration of 18–20 months and a treatment 
duration of 15–17 months after culture conversion were suggested for most patients, with the duration 
being modified according to the patient’s response to
therapy.
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Given that few trials or other studies have made head-to-head comparisons of MDR-TB medicines at different dosage regimens, it is 
not expected that guidance on dosage adjustment will be affected by the findings of the systematic
review.

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Recommendations 
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