Drug-resistant tuberculosis treatment

Rifampicin-resistant TB. A patient (child or adult) in whom isoniazid resistance is absent needs 
to be treated with a recommended MDR-TB regimen – either a longer MDR-TB regimen to which 
isoniazid is added, or a shorter MDR-TB regimen in eligible patients (see also 
Section 2
). While high-
dose isoniazid is not included in Groups A–C given the rarity of its use in contemporary longer 
regimens for adults with MDR/RR-TB, it may still be used in patients with confirmed susceptibility or 
in the presence of mutations that do not usually confer complete resistance to isoniazid (75). High-
dose isoniazid was shown to be an important component in paediatric regimens in a 2016 evidence 
review of the WHO guidelines, based on which its use in adults was extrapolated (62). In this analysis, 
high-dose isoniazid was associated with treatment success among children with confirmed MDR-TB 
(aOR: 5.9; 95% CL: 1.7–20.5, P=0.007).
Children. The 2018 IPD of longer regimens comprised mainly data from adult patients, with only 181 of 
the 13 104 (1.4%) cases being in children aged under 15 years. Nonetheless, WHO recommendations 
on longer MDR-TB regimens apply to children as well as adults. Most medicines that are used in 
longer regimens have been part of MDR-TB regimens for many years, in similar combinations, for 
both adults and children. The GDG recommended the use of bedaquiline in children aged at 
least 6 years, and delamanid in children aged at least 3 years (see 
Section 3.3
).
42
Reproducing 
the delamanid exposure achieved with the special 25 mg tablet tested in the trial in children aged 
3–5 years is expected to be challenging, given that this formulation is not bioequivalent with the 
50 mg delamanid adult tablet – the only preparation available in the foreseeable future (11). There 
are also concerns that the adult tablet may shatter if attempts are made to split it, and that its 
contents are exceedingly bitter and unpalatable. Further, bioavailability may be altered when the 
50 mg tablet is split, crushed or dissolved. Delamanid is susceptible to oxidation and heat; 
therefore, retaining pill fragments for use at a time other than the time of administration is likely to 
result in the delivery of lower-than-expected active compound and unspecified oxidation by-
products. The avoidance of an injectable-containing regimen is particularly desirable in children, 
especially those who are very young and those with mild disease (as determined by the absence 
of malnutrition), serious forms of extrapulmonary disease, cavitation on chest radiography or HIV 
infection. Hearing loss can have a permanent effect on the acquisition of language and the 
ability to learn at school; therefore, if amikacin or streptomycin use is resorted to in children, 
regular audiometry is required (the 2018 recommendation is primarily for
adults).
42 
Based on the results of an RCT conducted by the manufacturer, the US FDA has extended approval for the use of bedaquiline for children 
aged 5 years and above. However, these data have not yet been assessed by
WHO.

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Recommendations 
36
The recommendations on treatment duration apply also to children. Given that many patients in the 
paediatric age group may only be clinically diagnosed or have extrapulmonary disease, it is expected 
that treatment duration will largely be guided by Recommendation 3.15, subject to response to 
treatment. Shortening the total treatment duration to less than 18 months may be considered in the 
case of children without extensive disease (see