The current recommendations for the selection of treatment regimens for patients affected by MDR-/RR-TB, pre-XDR-TB and XDR-TB are (table 5) [75]: 1. BPaLM regimen (6 months all-oral treatment regimen of bedaquiline, pretomanid, linezolid and moxifloxacin): In patients with MDR-/RR-TB where fluoroquinolone susceptibility is presumed or documented this regimen should be the treatment of choice. It is possible to omit moxifloxacin and continue with the BPaL regimen for MDR-/RR-TB patients with confirmed fluoroquinolone resistance (based on the results of the ZeNiX-TB [71] and TB PRACTECAL [72] trials). When the regimen is BPaL from the start or is changed to BPaL, it can be extended to a total of 39 weeks (counting from the start of the therapy with BPaLM/BPaL). This extension is justified in cases of failure to convert culture between months 4 and 6 while on treatment alternatively, it can be based on the clinical judgement of the treating physician. Up to 1 month can be added to the overall treatment duration if there is a need to make up the missed doses [75]. 2. For those who are not eligible for the shorter BPaLM/BPaL regiments (table 5): 9-month all-oral treatment regimen consisting of bedaquiline (used for 6 months), in combination with levofloxacin/moxifloxacin, ethionamide, ethambutol, isoniazid (high-dose), pyrazinamide and clofazimine (for 4 months, with the possibility of extending to 6 months if acid-fast bacilli are still detectable in the patient’s sputum at the end of 4 months), followed by treatment with levofloxacin/moxifloxacin, clofazimine, ethambutol and pyrazinamide (for 5 months). TABLE 5 Factors to be considered for selection of treatment regimens for patients with MDR-/RR-TB Regimen MDR-/RR-TB fluoroquinolone susceptible Pre-XDR-TB XDR-TB Extensive PTB EPTB Age 14 years 6-month BPaLM/ BPaL Yes (BPaLM) Yes (BPaL) No Yes Yes – except TB involving CNS, miliary TB and osteoarticular TB No 9-month all-oral Yes No No No Yes – except TB meningitis, miliary TB, osteoarticular TB and pericardial TB Yes Longer individualised 18-month Yes #/No Yes #/No Yes Yes Yes Yes Additional factors to be considered if several regimens are possible Drug intolerance or adverse events Treatment history, previous exposure to regimen component drugs or likelihood of drug effectiveness Patient or family preference Access to and cost of regimen component drugs BPaL: bedaquiline, pretomanid and linezolid BPaLM: bedaquiline, pretomanid, linezolid and moxifloxacin CNS: central nervous system. #:when 6-month BPaLM/BPaL and 9-month regimens cannot be used. Reproduced and modified from [75] with permission. 128 https://doi.org/10.1183/2312508X.10024622 ERS MONOGRAPH |THE CHALLENGE OF TB IN THE 21ST CENTURY