rifapentine was available in only 6 (14%) out of 43 participating countries of the WHO European region [60]. In March 2023, the TRUNCATE-TB trial demonstrated that a treatment strategy with an 8-week intensified treatment regimen of bedaquiline (400 mg once daily for 2 weeks, then 200 mg three times a week), linezolid (600 mg), isoniazid, pyrazinamide, and ethambutol and treatment extension only in patients with persistent clinical disease was non-inferior to standard treatment for rifampicin-susceptible PTB with respect to clinical outcomes [61]. These promising results document that shorter treatment durations are possible for many patients. For paediatric patients, the 6-month regimen has been the standard of care [46–48]. In 2022, the open-label, randomised controlled SHINE trial showed that 6 months of anti-TB treatment with isoniazid, rifampicin and pyrazinamide, with or without ethambutol was non-inferior to 6 months of treatment in children younger than 16 years weighing ⩾3 kg with drug-susceptible, non-severe, smear-negative TB [62]. Non-severe TB was defined as non-cavitary PTB confined to one lobe without a miliary patern or complex pleural effusion, intrathoracic lymph node TB without airway obstruction, and peripheral lymph node TB. The WHO conditionally endorsed this shortened treatment regimen for children and adolescents between 3 months and 16 years of age with presumed drug-susceptible non-severe disease [5]. The use of ethambutol is recommended in settings with a high prevalence of isoniazid resistance as defined by the national TB programmes, or a high HIV prevalence (defined as ⩾1% among adult pregnant women or ⩾5% among TB patients) [46, 63]. In other settings, patients receiving the shortened regimen may be treated with a three-drug regimen for the first 2 months without ethambutol, if M. tuberculosis susceptibility to isoniazid and rifampicin is ensured by rapid molecular testing [64]. Treatment for rifampicin-susceptible, isoniazid-resistant TB A recent meta-analysis comprising 5418 patients with rifampicin-susceptible, isoniazid- resistant TB suggests that the addition of a fluoroquinolone is linked to improved treatment success [65]. Therefore, 6-month treatment with rifampicin, ethambutol, pyrazinamide, and levofloxacin is recommended in patients with confirmed rifampicin-susceptible, isoniazid-resistant TB (table 4) [46]. Levofloxacin is generally the fluoroquinolone of choice since it has frequently been used in studies and has fewer drug interactions than other fluoroquinolones. For example, moxifloxacin plasma concentration significantly decreases when combined with rifampicin [66]. In cases of noncavitary disease, low disease burden, or pyrazinamide toxicity, the American Thoracic Society (ATS), US Centers for Disease Control and Prevention (CDC), European Respiratory Society (ERS), and Infectious Diseases Society of America (IDSA) suggest that treatment with pyrazinamide may be reduced to 2 months [48]. Patients with fluoroquinolone resistance or contraindications for fluoroquinolone treatment are generally recommended to be treated with 6 months of rifampicin, ethambutol, and pyrazinamide [46]. The use of high-dose isoniazid is not recommended in geographic regions where isoniazid resistance is based on katG mutations in the great majority of patients, e.g. the WHO European region [9, 67]. When additional drug resistance is suspected or confirmed, individual treatment regimens need to be designed. TABLE 4 Treatment regimen for rifampicin-susceptible, isoniazid-resistant PTB Drugs Duration months R Lfx Z E 6 R: rifampicin Lfx: levofloxacin Z: pyrazinamide E: ethambutol. 126 https://doi.org/10.1183/2312508X.10024622 ERS MONOGRAPH |THE CHALLENGE OF TB IN THE 21ST CENTURY