Treatment against DS-TB in children and adults The traditional regimen for treating adults with TB caused by organisms that are not known or that are suspected to be drug-resistant consists of a 2-month intensive phase with isoniazid, rifampicin, pyrazinamide and ethambutol, followed by a 4-month continuation phase with isoniazid and rifampicin (table 2) [46–48]. However, it is advised to continue the quadruple therapy if acid-fast bacilli are still detectable from sputum at the end of the second month until drug susceptibility to isoniazid and rifampicin is confirmed or until acid-fast bacilli are no longer detectable in a sputum specimen. Patients with extensively advanced or cavitary disease and/or those with a delayed culture conversion may benefit from prolongation of the continuation phase to reduce the chance of a relapse. It has been recommended to extend the continuation phase of treatment for at least 4 months beyond the time when acid-fast bacilli become undetectable from sputum specimen [49]. Approximately 85% of patients achieve a successful treatment outcome with this regimen, which has been widely used worldwide for decades [1]. These recommendations also apply to patients with EPTB, except for central nervous system disease and bone and joint disease, for which longer treatment durations are recommended by some expert groups. Whenever feasible, fixed-drug combination tablets are preferred over separate drug formulations [50]. Daily therapy is favoured over intermittent therapy since it provides higher cure rates and a lower risk of disease relapse and drug-acquired resistance than thrice-weekly or twice-weekly dosing regimens [51–57]. Dosagesof different medicines are shown in table 3. An open-label, randomised controlled trial in 2021 indicated that a 4-month regimen with rifapentine, moxifloxacin, isoniazid, and pyrazinamide was non-inferior to the standard 6-month regimen in terms of efficacy and safety [58]. Consequently, the WHO endorsed this 4-month regimen as a treatment option for nonpregnant patients aged ⩾12 years with body weight ⩾40 kg, with drug-susceptible PTB [5]. This shorter treatment regimen has the potential to reduce the burden on healthcare systems, increase treatment adherence and allow faster cure. However, implementation and uptake are hampered by the limited availability of rifapentine. As of March 2020, rifapentine has been registered only in 13 countries worldwide [59]. A recent survey within the TB Network European Trials group (TBnet) showed that by October 2021, TABLE 2 Treatment regimens for drug-susceptible PTB Regimen Intensive phase Continuation phase Comment Drugs Duration, months Drugs Duration, months Regimen 1 H R Z E 2 H R 4 Traditional regimen Regimen 2 H Rpt Z Mfx 4 Endorsed for nonpregnant patients aged ⩾12 years with body weight ⩾40 kg with drug-susceptible PTB by the WHO Regimen 3 H R Z (E) 2 H R 2 Endorsed for children and adolescents between 3 months and 16 years of age with presumed drug-susceptible non-severe disease by the WHO H: isoniazid R: rifampicin Z: pyrazinamide E: ethambutol Rpt: rifapentine Mfx: moxifloxacin. 122 https://doi.org/10.1183/2312508X.10024622 ERS MONOGRAPH |THE CHALLENGE OF TB IN THE 21ST CENTURY