Drug-resistant tuberculosis treatment

PICO question 4 (MDR/RR-TB, 2018) (number of agents likely to be effective). To analyse 
treatment success, treatment failure, relapse and death for the optimal number of medicines to be 
included in longer regimens, the data were derived from a subset of 8957 patients in 47 studies 
included in the IPD used for PICO question 2 (MDR/RR-TB, 2018) above. Of these, 3570 patients in 
16 studies had information on the start and end dates for individual medicines in which DST was 
reported, and 5387 patients in 31 studies had information on individual medicines used in both the 
intensive and continuation phases of treatment, as well as DST results. As this question focused on 
the number of agents in the intensive phase, patients who did not receive an injectable agent or in 
whom an initial intensive phase was not defined were excluded (n=476). Patients who were designated 
“cured” or “treatment completed” but received less than 18 months of treatment – the minimum 
duration for longer regimens recommended by WHO in the past – were also excluded (n=346). 
In cases where DST results were available, a medicine was considered effective if results showed 
susceptibility, and was considered not effective if results showed resistance. Where DST results were 
missing, two situations existed. First, if the prevalence of resistance to that medicine was less than 
10% in the same population (i.e. from the same country or study site if within one country, or overall 
at all sites if local data were not available), then the medicine was counted as effective. This situation 
applied to the following agents: cycloserine or terizidone, linezolid, clofazimine, bedaquiline, the 
carbapenems and delamanid. Second, if the prevalence of resistance to that medicine was more than 
or equal to 10% in the same population (from the same country or study site if within one country, or 
overall at all sites if local data were not available), then imputed DST results were used to determine 
effectiveness if DST was missing. If the imputed DST result showed susceptibility, then the medicine 
was counted as effective; if the imputed DST result showed resistance, then the medicine was not 
counted as effective. This situation applied to the following agents: pyrazinamide, ethambutol, second-
line injectable agents, fluoroquinolones, p-aminosalicylic acid, ethionamide and prothionamide. The 
following were not included when counting the number of medicines likely to be effective (regardless 
of any DST result that may have been available): isoniazid (including high-dose isoniazid), rifampicin, 
rifabutin, thioacetazone, amoxicillin–clavulanate and macrolide
antibiotics.

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WHO consolidated 
guidelines 
on
tuberculosis: 
drug-resistant tuberculosis treatment
25
Subsets of the main 2018 IPD meta-analysis with 13 104 patients overall from 53 studies in 40 countries 
were analysed for the risk of treatment failure and relapse versus success associated with different 
durations in these three recommendations on the duration of treatment (see Annex 3 and Annex 4 
for the GRADE tables, and Annex 6 for the analysis plan). Patients followed up for relapse and the 
number reported with relapse were relatively small. The three IPD subsets for PICO questions 4, 5 
and 6 are discussed
below.