Treatment interruptions — MSF Tuberculosis

What this guideline says

GMJ summary

This section of the MSF tuberculosis guideline addresses the management of treatment interruptions in patients with multidrug-resistant and rifampicin-resistant tuberculosis (MDR/RR-TB). Treatment interruptions pose significant risks: they may lead to the emergence of new drug resistances, and drugs with long half-lives such as bedaquiline or clofazimine remain in the blood for several months after interruption, effectively creating functional monotherapy that increases resistance risk.

The guidance stratifies management by duration of interruption. Patients who interrupt treatment for 2 months or more are classified as “lost to follow-up” and require repeat bacteriological testing (rapid molecular test, culture and full phenotypic drug susceptibility testing and/or genome sequencing) upon return, with initiation of a new regimen based on rapid molecular test results whilst awaiting full results. For interruptions of 4 weeks or more but less than 2 months, the same testing is required, but clinicians may either start a new regimen or resume the interrupted treatment based on clinical status and rapid molecular test results, with missed doses made up if treatment is resumed.

The guideline emphasises the importance of detecting and addressing the underlying causes of treatment interruption, including management of adverse effects and reinforcement of patient support measures.

Key points

For clinicians — doses and thresholds as stated in the guideline

1. Treatment interruptions may lead to emergence of new drug resistances, particularly to bedaquiline and clofazimine which remain in blood for several months after interruption.
2. Patients interrupting treatment for 2 months or more meet the definition of "lost to follow-up" and require repeat bacteriological tests (rapid molecular test, culture, full phenotypic drug susceptibility testing and/or genome sequencing) upon return.
3. For interruptions of 2 months or more: start a new regimen based on rapid molecular test results whilst waiting for full drug susceptibility test results, then adjust treatment accordingly.
4. For interruptions of 4 weeks or more but less than 2 months: perform new bacteriological tests and either start a new regimen or resume interrupted treatment based on clinical status and rapid molecular test results.
5. If interrupted treatment is resumed after 4 weeks to 2 months, all doses missed during the interruption must be made up to complete the full treatment course.
6. Actively detect and address problems causing treatment interruptions, including management of adverse effects and reinforcement of patient support measures.
7. Long half-life drugs (bedaquiline, clofazimine) create a functional monotherapy situation after treatment interruption, substantially increasing resistance development risk.

From the guideline

Verbatim

“In practice, it is as if the patient is receiving bedaquiline and/or clofazimine alone, which increases the risk of developing resistance to these drugs.”

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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