Tables
- TABLE 1
Historical list of recommended regimens for multidrug-resistant (MDR)/extensively drug-resistant (XDR) tuberculosis (TB)
Name Year Main features/regimens Length of treatment [Ref.] DOTS-PLUS 2000 Rational use of second-line drugs in resource-limited settings
GLC to facilitate access to proven quality second-line anti-TB drugs to overcome difficulties in procurement and cost
[6, 7] Guidelines for the programmatic management of drug-resistant TB 2006 Management of MDR-TB to be integrated into comprehensive national TB control plans
First “modern” categorisation of drugs used to treat MDR-TB into five groups
Options for tailoring diagnosis and care to different epidemiological and programmatic conditions worldwide
18 months after culture conversion [9] Guidelines for the programmatic management of drug-resistant TB: emergency update 2008 Definition of XDR and acknowledgement of this threat
Recommendations on drug resistant management
Introduction of rapid DST
[10] WHO guidelines for the programmatic management of drug-resistant TB: 2011 update 2011 Importance of rapid DST stressed
Regimens including at least four, and ideally five, drugs likely to be effective
Drugs to be included are a FLQ, an injectable agent, ethionamide or prothionamide, PZA and either cycloserine or para-amniosalicylic acid. Other drugs such as EMB or group 5 drugs could be added, but they should not be counted among the four effective drugs
20 months (with an 8-month intensive phase) [11] WHO consolidated guidelines on drug-resistant TB treatment 2019 Continued recommendation of using shorter regimen whenever possible
If using injectables use amikacin
Drugs reclassified into three groups (A, B and C) for the purpose of composing the longer regimen: Group A includes three drugs to be prioritised and used, if possible, in all regimens: levofloxacin/moxifloxacin, BDQ and LZD Group B includes two drugs to be possibly added to all regimens (CFZ and cycloserine/terizidone) Group C includes “other” agents (including injectables) to be used as a substitute to complete a regimen of at least four drugs when agents from groups A and B cannot be used
Longer regimen: may be standardised or individualised; duration 18–20 months, modified depending upon patient response
Shorter regimen: 9–12 months[32] WHO: World Health Organization; RR: rifampicin-resistant; GLC: Green Light Committee; DST: drug susceptibility testing; FLQ: fluoroquinolone; PZA: pyrazinamide; EMB: ethambutol; CFZ: clofazimine; BDQ: bedaquiline; LZD: linezolid.
- TABLE 2
Innovative ongoing trials for an “all-oral” treatment of multidrug-resistant (MDR)/extensively drug-resistant (XDR) tuberculosis (TB)
Trial number/name Type of TB (MDR/XDR) Study phase Regimens studied Promoter Duration of new regimen Status Patients n 1 Nix# XDR 3 Pretomanid, bedaquiline and linezolid TB Alliance 6 months Ongoing >75¶ 2 ZeNix XDR 3 Pretomanid, bedaquiline and linezolid (linezolid treatment dose and duration are double-blinded) TB Alliance 26 weeks Enrolling 180 (estimated) 3 STREAM MDR 3 A: local WHO standard
B: clofazimine, ethambutol, moxifloxacin and pyrazinamide (40 weeks) + isoniazid, kanamycin and prothionamide (first 16 weeks)
C: bedaquiline, clofazimine, ethambutol, levofloxacin and pyrazinamide (40 weeks) + isoniazid and prothionamide (first 16 weeks)
D: bedaquiline, clofazimine, levofloxacin and pyrazinamide (28 weeks) + isoniazid and kanamycin (first 8 weeks)IUATLD 36/56 weeks Enrolling Currently >300 4 NeXT MDR 3 Linezolid, bedaquiline, levofloxacin, pyrazinamide + ethionamide or terizidone or high-dose INH South African investigators 6–9 months Not yet recruiting 300 (estimated) 5 TB PRACTECAL MDR/XDR 2–3 A: local WHO standard
B: bedaquiline and pretomanid + linezolid, moxifloxacin
C: bedaquiline and pretomanid + linezolid, clofazimine
D: bedaquiline and pretomanid + linezolidMSF 6 months Enrolling Currently >100 (630 estimated) 6 End TB MDR 3 A: bedaquiline, linezolid, moxifloxacin, pyrazinamide
B: bedaquiline, linezolid, clofazimine, levofloxacin, pyrazinamide
C: bedaquiline, delamanid, linezolid, levofloxacin, pyrazinamide
D: delamanid, clofazimine, levofloxacin, linezolid, pyrazinamide
E: delamanid, clofazimine, moxifloxacin, pyrazinamide
F: local WHO standard, including the possible use of bedaquiline or delamanidMSF and PIH 9 months Enrolling Currently >170 (750 estimated) 7 SimpliciTB MDR (or single resistance to isoniazid or rifampicin) 2 Bedaquiline, pretomanid, moxifloxacin, pyrazinamide TB Alliance 6 months Enrolling Currently >10 (150 estimated) 8 MDR-END MDR 2 Delamanid, linezolid, levofloxacin and pyrazinamide versus local WHO standard Seoul National University Hospital 9–12 months Enrolling (238 estimated) IUATLD: International Union Against Tuberculosis and Lung Diseases; MSF: Médecins Sans Frontières; PIH: Partners In Health; WHO: World Health Organization; INH: isoniazid: #: definitive results pending; ¶: information reported only for this number of patients.
