Drug-resistant tuberculosis treatment

Clavulanic acid – this medicine should be included in MDR/RR-TB regimens only as a companion 
agent to the carbapenems (imipenem–cilastatin and meropenem). When used in this way, it should 
be given with every dose of carbapenem, and should not be counted as an additional effective 
TB
agent.
No recommendation on perchlozone, interferon gamma or sutezolid was possible owing to the 
absence of final patient treatment outcome data from appropriate patient
studies.
Regarding the use of bedaquiline in patients aged under 18 years, and considering that exposure– 
response (efficacy) profiles can be extrapolated from adults to children, the GDG concluded that the 
doses evaluated in children and adolescents in two trials (Phase II trial TMC207-C211 and Phase I/ 
II IMPAACT P1108; see Annex 5) do not appear to result in exposures that would put patients aged 
6–17 years at increased risk for treatment failure. The safety risk in children aged 6 years or more 
enrolled in the trials – who were all HIV-negative and had limited exposure to other QT interval-
prolonging medications – did not appear to exceed that of adults. The variability present in the 
limited sample size precluded a comment on exposure–response (safety). The GDG also concluded 

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Recommendations 
28
that the risk–benefit considerations for the use of bedaquiline in patients aged 6–17 years are similar 
to those considered for adults, but stressed the need for more data before considering an upgrade 
of this recommendation to a strong
one.
With respect to the use of delamanid in children aged under 6 years, the GDG decided that on the basis 
of findings in adults, and on the pharmacological and safety data reviewed, extrapolations on efficacy 
and safety should be restricted to children aged 3–5 years, but not to children aged under 3 years 
(see Annex 5). Exposure profiles in children aged 3–5 years were comparable to adults, and were no 
higher than in children aged 6 years or more, for whom past GDGs convened by WHO had already 
recommended the use of delamanid (9, 70). Based on the laboratory and cardiac data provided, no 
safety signals distinct from those reported in adults were observed in children aged 3–5 years. The 
GDG nonetheless had concerns about the feasibility of administering the correct dose to children 
aged 3–5 years, given that the special formulation used in the trial (25 mg) would not be available in 
the foreseeable future, and that only the adult tablet is available (50 mg), which is not bioequivalent 
and presents challenges to manipulating its contents without compromising its
effectiveness.