Drug-resistant tuberculosis treatment

Section 1. Regimen for rifampicin-susceptible, 
isoniazid-resistant tuberculosis 
1.1 Recommendations
No.
Recommendation
1.1
In patients with confirmed rifampicin-susceptible, isoniazid-resistant tuberculosis 
(Hr-TB), treatment with rifampicin, ethambutol, pyrazinamide and levofloxacin is 
recommended for a duration of 6
 
months.
(Conditional recommendation, very low certainty in the estimates of
 
effect)
1.2
In patients with confirmed rifampicin-susceptible, isoniazid-resistant tuberculosis, 
it is not recommended to add streptomycin or other injectable agents to the 
treatment
 
regimen.
(Conditional recommendation, very low certainty in the estimates of
 
effect)
1.2 Justification and evidence
The recommendations in this section address one PICO (population, intervention, comparator and 
outcomes) question:
PICO question 1 (Hr-TB, 2018): In patients with isoniazid-resistant TB (other than MDR-TB), 
which treatment regimen composition and duration, when compared with 6 months or more of 
rifampicin–pyrazinamide–ethambutol, leads to a higher likelihood of success with least possible 
risk of
 
harm?
Treatment with rifampicin, ethambutol and pyrazinamide – with or without isoniazid – has been 
used for the treatment of patients with rifampicin-susceptible, isoniazid-resistant TB (Hr-TB) (14–16). 
The evidence reviewed for this guideline compared treatment regimens with isoniazid, rifampicin, 
ethambutol, pyrazinamide ((H)REZ)
18
of different durations (e.g. 6-month regimens versus longer 
duration ones). Additionally, the review of evidence focused on determining whether treatment 
outcomes in Hr-TB patients receiving (H)REZ treatment regimens of variable duration could be 
improved with the addition of a fluoroquinolone or
streptomycin.
The evidence used to determine the composition and duration of regimens relied primarily on an 
analysis of IPD that comprised 33 databases with an analysable population of 5418 Hr-TB patients. All 
data used to develop these recommendations were derived from observational studies conducted in 
various settings (33% in Europe, 31% in the Americas, 26% in Asia and 6% in Africa) (17).
19
In the IPD 
18 
“(H)” indicates that isoniazid is optional. 
19 
The number of patients highlighted in this section refers to the sample size of each study. However, the analysable sample size was 
later modified, depending on the availability of IPD for each analysable outcome (success and
mortality).

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WHO consolidated 
guidelines 
on
tuberculosis: 
drug-resistant tuberculosis treatment
5
analysed, patient treatment regimens contained rifampicin, ethambutol, pyrazinamide, streptomycin, 
isoniazid and fluoroquinolones; thus, recommendations could be made only for regimens containing 
these anti-TB agents. Based on an assessment of the certainty of the evidence, carried out using 
predefined criteria, the certainty of the evidence was rated as very
low.