Treatment adaptation and change of treatment — MSF Tuberculosis

What this guideline says

GMJ summary

This section of the MSF Tuberculosis guideline distinguishes between treatment adaptation (minor modifications that do not constitute treatment failure) and treatment change (switch to a different regimen that typically meets the definition of treatment failure). Treatment adaptation includes temporary interruption of any drug, permanent interruption of linezolid less than 8 weeks before treatment end or pyrazinamide in short treatment regimens (STRs), or change of one drug class in longer treatment regimens (LTRs).

Treatment change—defined as switching from one STR to another STR or LTR, or from one LTR to another—is required when new resistance emerges after treatment initiation, resistance is not detected at baseline, bacteriological conversion fails or reversion occurs, or when severe adverse effects necessitate permanent interruption of key drugs. For STRs, this includes permanent interruption of bedaquiline, pretomanid, delamanid, levofloxacin/moxifloxacin, clofazimine, or linezolid more than 8 weeks before treatment end. For LTRs, change of at least 2 drug classes constitutes treatment change.

The guideline emphasises maintaining at least 4 to 5 likely effective drugs in LTRs, with special provisions for drug substitution during the first 6 months versus after. Treatment changes meet the outcome definition of treatment failure except when the reason is resistance not detected at baseline.

Key points

For clinicians — doses and thresholds as stated in the guideline

1. Treatment adaptation for STRs includes permanent interruption of linezolid less than 8 weeks before treatment end, permanent interruption of pyrazinamide, or temporary interruption of any individual drug
2. For LTRs, at least 4 to 5 likely effective drugs are needed; if a Group A drug is discontinued in the first 6 months, replace it with the most effective remaining TB drug
3. After 6 months in LTRs, if clinical status has improved and bacteriological tests are negative, treatment may continue if it still includes at least 3 drugs from Group A and/or B
4. Treatment must be changed if new resistance emerges after treatment initiation (e.g. fluoroquinolone resistance appearing at Month 2 DST when baseline showed susceptibility)
5. For STRs, permanent interruption of bedaquiline, pretomanid, delamanid, levofloxacin/moxifloxacin, clofazimine, or linezolid more than 8 weeks before treatment end requires treatment change
6. For LTRs, change of at least 2 drug classes in the regimen constitutes treatment change rather than adaptation
7. Treatment change is required for no bacteriological conversion or bacteriological reversion, or insufficient clinical response in non-bacteriologically confirmed TB
8. Treatment changes meet the definition of treatment failure except when the reason is resistance not detected at baseline

From the guideline

Verbatim

“If the DST at Month 2 shows fluoroquinolone resistance, while the DST at baseline showed fluoroquinolone susceptibility, the treatment must be changed.”

Editor’s perspective

Why this matters for Georgia and the region

Applicability

Georgia and the South Caucasus

Questions this guideline answers

Quick answers

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