TABLE 1.
Summary of 2 decades of changes to DR-TB treatment regimensa
| Guideline | Recommended regimen composition | Treatment duration | New recommendations |
|---|---|---|---|
| Guidelines for establishing DOTS-PLUS pilot projects for management of MDR-TB (20) | MDR-TB standard regimen 6 mo EMB-OFX-PZA-CM-ETO/PAS/CS 12 mo EMB-OFX-ETO/PAS/CS |
18 mo | • Recommendations for standardized and individualized treatment approaches • Regimens to contain at least 3 effective drugs including an injectable agent • DST to be performed at baseline and every 3 mo thereafter until patient converts to consecutive negative sputum |
| MDR-TB standard regimen (Peru), 3 mo KAN-CFX-ETO-PZA-EMB 15 mo KAN-ETO-Z-EMB |
18 mo | ||
| MDR-TB regimen when waiting for DST 6 mo HREZ + CM + OFX ± PAS |
6 mo | ||
| INH monoresistant or INH- and STR-resistant regimen 2 mo HREZ 7 mo RE |
9 mo | ||
| INH, EMB, streptomycin resistance regimen 2 mo RIF-OFX-PZA-CM 7 mo RIF-OFX-PZA |
9 mo | ||
| DS-TB regimen, 2–3 mo HREZ 2–3 mo HREZ/4HR |
4–6 mo | ||
| Guidelines for programmatic management of drug-resistant TB, 2006 (21) | RR/MDR-TB standardized regimen, 8 mo KAN-OFX-PTO-CS 12 mo OFX-PTO-CS |
20 mo | • Implementation of standardized and individualized DR-TB regimens |
| Guidelines for programmatic management of DR-TB, emergency update, 2008 (23) | Standardized MDR-TB regimen, 6 mo Z-KAN (CM)-OFX-ETO-CS 12 mo PZA-OFX-ETO-CS |
18 mo | • CFX removed from DR-TB regimen due to weak efficacy, especially compared to other FQs |
| WHO guidelines for programmatic management of DR-TB, 2011 update (24) | RR/MDR-TB regimen, 8 mo PZA-MFX-KAN-ETO/PTO-CS/PAS 12 mo PZA-MFX-ETO/PTO-CS/PAS |
20 mo | • Recommended 8-mo intensive phase • EMB removed from standard DR-TB regimen, with option for use • Early antiretroviral treatment for HIV-DR TB coinfected patients |
| WHO treatment guidelines for DR-TB, 2016 update (31) | INH resistance, 6–9 mo HRZE or 6–9 mo RZE |
6–9 mo | • First standardized short regimen for specific indicationsc • Shorter MDR-TB regimen recommended under specific conditionsc • Use of high-dose INH and/or E for regimen strengthening • DR-TB drugs regrouped based on effectiveness and safety; • CFZ and LZD recommended as core second-line drugs; • PAS grouped as add-on agent • BDQ and DLM also assigned to specific add-on agent subgroup |
| Shorter RR/MDR-TB regimen, 4–6 mo KAN-MFX-PTO-CFZ-INHhd-EMB 5 mo MFX-CFZ-PZA-EMB |
9–11 mo | ||
| Longer MDR-TB regimen, 8 mo PZA-MFX-KAN-CFZ-EMB 12 mo MFX-CFZ-EMB-PZA |
20 mo | ||
| Key changes to treatment of MDR/RR-TB, 2018 rapid communication (33) | Longer standardized regimen,b 6–8 mo LZD-BDQ-LFX-CFZ-TZD 12 mo LFX-CFZ-TZD |
18–20 mo | • Revised grouping of anti-TB drugs for longer regimens • All-oral long regimen for RR/MDR-TB • Group A (LFX/MFX, BDQ, and LZD), group B (CFZ, CS, and TRD), and group C (EMB, PZA, imipenem-cilastatin, AMK (STR), ETO/PTO, PAS, DLM) • KAN and CM no longer recommended |
| Shorter MDR-TB regimen, mainly standardized, injection based 4–6 mo AM-MFX-PTO/ETO-CFZ-PZA-INHhd-EMB 5 mo MFX-CFZ-PZA-EMB |
9–11 mo | ||
| Key changes to treatment of DR-TB, 2019 rapid communication (14) | All-oral shorter regimen, 4–6 mo BDQ-LFX (or MXF)-LZD, INHhd-CFZ-EMB-PZA 5 mo LFX-CFZ-EMB-PZA Novel treatment regimen, BPaL |
9–11 mo 6–9 mo |
• Transitioning to short-course injection-free regimen • Injectable agent replacement by BDQ • The first-ever short, 6-mo, all-oral regimen for XDR and unresponsive MDR-TB treatment (under research conditions) |
| WHO consolidated guidelines on DR-TB treatment, 2019 (34) | INH-monoresistant standardized regimen, 6 mo RZE + LFX |
6 mo | • Use of an FQ in INH-monoresistant TB regimen • Use of LFX instead of MFX • Grouping of anti-TB drugs remains the same |
| RR/MDR-TB, Shorter-course, all-oral for eligible MDR/RR-TB patients, standard regimen composition of 4–6 mo BDQ-LFX-LZD, INHhd-CFZ-EMB- 5 mo LFX-CFZ-EMB-PZA |
9–11 mo | ||
| RR/MDR-TB, Injection-containing shorter-course regimen, 4 mo AMK-MFX-CFZ-INHhd-PTO-EMB-PZA 5 mo MFX-CFZ-EMB-PZA |
9 mo | ||
| RR/MDR-TB, Long-course all-oral regimen,b RR-TB, MDR-TB, and pre-XDR-TB (second-line resistance) 6 mo BDQ-LFX-CFZ-LZD 12 mo LFX-CFZ-LZD |
18 mo | ||
| RR/MDR-TB, Long-course individualized regimen,b pre-XDR-TB (FQ resistance) and XDR-TB, 6–8 mo BDQ-CFZ-LZD-DLM-TRD-PZA-INHhd 12 mo CFZ-LZD-TRD-PZA-INHhd |
18–20 mo | ||
| WHO consolidated guidelines on DR-TB treatment, 2020 (5) | Short all-oral RR/MDR-TB regimen, 6 mo BDQ 4–6 mo LFX/MFX-CFZ-PZA-EMB-INHhd-ETO 5 mo LFX/MFX-CFZ-PZA-EMB |
9–11 mo | • Safety on extended use of BDQ beyond 6 mo • Guidance on BDQ use during pregnancy |
| BPaL, 6–9 mo BDQ-PTM-LZD | 6–9 mo | ||
| Key changes to the treatment of DR-TB, 2022 rapid communication (15) | BPaL regimen, BDQ-PTM-LZD BPaLM regiman, BDQ-PTM-LZD-MFX |
6–9 mo | • Programmatic use of BPaL and BPaLM for RR/MDR-TB and pre-XDR-TB |
DST, drug susceptibility testing; DR-TB, drug-resistant TB; HR-TB, isoniazid monoresistant TB; RR-TB, rifampin-resistant TB; MDR-TB, multidrug-resistant TB; XDR, extensively drug-resistant TB; HREZ, isoniazid, rifampin, ethambutol, pyrazinamide; RIF, rifampin; STR, streptomycin; AM, amikacin; PAS, p-amino salicyclic acid; KAN, kanamycin; CM, capreomycin; OFX, ofloxacin; CFX, ciprofloxacin; ETO, ethionamide; CS, cycloserine; LFX, levofloxacin; BDQ, bedaquiline; MXF, moxifloaxcain; LZD, linezolid; INHhd, high-dose isoniazid; CFZ, clofazimine; EMB, ethambutol; PZA, pyrazinamide; PTO, prothionamide; ETO, ethionamide; DLM, delamanid; TRD, teridizone; BPaL, bedaquline-pretomanid-linezolid; BPaLM, bedaquiline-pretomanid-linezolid-moxifloxacin.
Longer regimens are recommended when construction of MDR/RR-TB regimen with three group A and two group B drugs is not possible due to intolerance to the medicines, acquired additional resistance, etc.
Standardized short regimen is recommended for patients who have not been previously treated for >1 month with second-line drugs used in the shorter MDR-TB regimen or in whom resistance to fluoroquinolones and second-line injectable agents has been excluded; a shorter MDR-TB regimen of 9 to 12 months may be used instead of the longer regimens.