The GDG assessed the individual contribution to patient outcomes of medicines used in longer MDR-TBregimens using primarily the estimates of effect from the 2018 IPD-MA and Trial 213 (delamanid) forPICO question 2 (MDR/RR-TB, 2018; see online Annexes 7 and 8 for the respective GRADE [Gradingof Recommendations Assessment, Development and Evaluation] summaries of evidence for eachmedicine as well as the evidence-to-decision framework). Following a thorough assessment of therelative benefits and harms, recommendations were made for each medicine and they were classifiedinto three groups (see Tables 2.1–2.3).– Group A: fluoroquinolones (levofloxacin and moxifloxacin), bedaquiline and linezolidwere considered highly effective and strongly recommended for inclusion in all regimensunless contraindicated.– Group B: clofazimine and cycloserine or terizidone were conditionally recommended as agentsof second choice.– Group C: included all other medicines that can be used when a regimen cannot be composedwith Group A and B agents. The medicines in Group C are ranked by the relative balance ofbenefit to harm usually expected of each.Other medicines that are not included in Groups A–C are:– kanamycin and capreomycin, which were associated with poorer outcomes when used and aretherefore no longer recommended for use in MDR-TB regimens;– gatifloxacin and high-dose isoniazid were used in very few patients and thioacetazone was notused at all. Quality-assured preparations of gatifloxacin are not currently available following itswithdrawal from the market due to concerns about dysglycaemias. Thioacetazone is unlikely tohave a role in contemporary longer regimens and is not currently available in a quality-assuredformulation. High-dose isoniazid may have a role in patients with confirmed susceptibility toisoniazid (see under Subgroup considerations later in this chapter);– clavulanic acid should be included in MDR/RR-TB regimens only as a companion agent to thecarbapenems (imipenem–cilastatin and meropenem). When used in this way, it should be givenwith 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 theabsence of final patient treatment outcome data from appropriate patient studies.Regarding the use of bedaquiline in patients younger than 18 years, and considering that exposure–response (efficacy) profiles can be extrapolated from adults to children, the GDG concluded that thedoses evaluated in children and adolescents in two trials (Phase II trial TMC207-C211 and Phase I/II IMPAACT P1108; see online Annex 9) do not appear to result in exposures that would put patientsaged 6–17 years at increased risk for treatment failure. The safety risk in children down to 6 years ofage enrolled in the trials – who were all HIV negative and with limited exposure to other QT-interval-prolonging medications – did not appear to exceed that of adults. The variability present in thelimited sample size precluded a comment on exposure–response (safety). The GDG also concludedthat the risk–benefit considerations for the use of bedaquiline in patients aged 6–17 years are similarto those considered for adults but stressed the need for more data before considering an upgradeof this recommendation to a strong one.With respect to the use of delamanid in children younger than 6 years, the GDG decided that on thebasis of findings in adults and on the pharmacological and safety data reviewed, extrapolations onefficacy and safety should be restricted to children aged 3–5 years but not to children younger than 3years (see online Annex 9). Exposure profiles in children 3–5 years of age were comparable to adultsand no higher than in children 6 years of age and older, for whom past GDGs convened by WHO hadalready recommended the use of delamanid (4,5). 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 childrenaged 3–5 years, given that the special formulation used in the trial (25 mg) would not be available inthe foreseeable future and only the adult tablet is available (50 mg), which is not bioequivalent andpresents challenges to manipulating its contents without compromising its effectiveness.