10.8 Treatment adaptation and change of treatment

10.8.1 Treatment adaptation

Treatment adaptation may be done by the clinician in case of severe adverse effects (Appendix 17). The following are considered treatment adaptations:

• For BPaLM and BPaL:
  • permanent interruption of linezolid after Month 4, or
  • interruption < 2 consecutive weeks or < 4 nonconsecutive weeks of individual drug(s) or the whole treatment.
• For 9-month bedaquiline-containing regimens:  
  • temporary interruption of individual drug(s) or the whole treatment, or
  • permanent interruption of ethambutol or pyrazinamide during the continuation phase.
• For LTRs:
  • temporary interruption of individual drug(s) or the whole treatment, or
  • change of one drug class in the regimen (no more than one).

 

In an LTR, at least 4 to 5 likely effective drugs are needed (Box 10.3). If any of these drugs must be permanently stopped:

• during the first 6 months, the regimen should be modified while maintaining the required number of likely effective drugs.
• after the first 6 months, if the patient clinical status has improved and bacteriological tests are negative, the clinician can decide to continue the treatment if it still includes at least 3 drugs from Group A and/or B.

 

These modifications are considered as treatment adaptations (not treatment changes, see Section 10.8.2) as they do not meet the definition of "treatment failure" (Chapter 17).

10.8.2 Change of treatment

Treatment change is defined as the switch from an STR to an LTR or from an LTR to a newly designed LTR.

 

Treatment should be changed by the clinician in the following circumstances [1] Citation 1. World Health Organization. Meeting report of the WHO expert consultation on drug-resistant tuberculosis treatment outcome definitions, 17-19 November 2020. Geneva: World Health Organization; 2021.
https://www.who.int/publications/i/item/9789240022195 :

• Emergence of a new resistance after treatment initiation.
• Resistance not detected at baseline for any reason.
• No bacteriological conversion or bacteriological reversion (Chapter 17).
• Insufficient clinical response to treatment in patients:
  • with no bacteriologically confirmed TB (e.g. miliary TB, some forms of EPTB, children);
  • with bacteriologically confirmed TB when bacteriological response cannot be assessed, or the result is inconclusive.
• Drug interruption due to severe adverse effects [2] Citation 2. World Health Organization. WHO operational handbook on tuberculosis. Module 4: treatment - drug-resistant tuberculosis treatment, 2022 update.
  https://www.who.int/publications/i/item/9789240065116 :
  • For BPaLM and BPaL:
    • permanent interruption of bedaquiline or pretomanid, or
    • permanent interruption of linezolid before the end of Month 4, or
    • interruption ≥ 2 consecutive weeks or ≥ 4 nonconsecutive weeks of the whole treatment.
  • For 9-month bedaquiline-containing regimens:  
    • permanent interruption of bedaquiline, levofloxacin/moxifloxacin, linezolid, ethionamide or clofazimine, or
    • permanent interruption of both ethambutol and pyrazinamide.
  • For LTRs: change of at least 2 drug classes in the regimen.

 

Note: for BPaLM regimen, if moxifloxacin must be interrupted, see the note in Section 10.2.1.

 

Treatment changes meet the outcome definition of "treatment failure" (Chapter 17), except when the reason for change is a resistance not detected at baseline [1] Citation 1. World Health Organization. Meeting report of the WHO expert consultation on drug-resistant tuberculosis treatment outcome definitions, 17-19 November 2020. Geneva: World Health Organization; 2021.
https://www.who.int/publications/i/item/9789240022195 .