From Tuberculosis › Chapter 11: Treatment of rifampicin-susceptible and isoniazid-resistant tuberculosis · Médecins Sans Frontières, Current online edition, 2026
MSF guidance on when and how to initiate treatment for Hr-TB in children and adults with pulmonary and extrapulmonary tuberculosis.
- Issuer
- Médecins Sans Frontières
- Edition
- Current online edition, 2026
- Audience
- Clinicians treating tuberculosis in MSF field settings and similar resource-limited contexts
- Evidence
- Based on individual patient data meta-analysis and WHO operational handbook recommendations
- Reviewed
- 23 Oct 2026 · GMJ
What this guideline says
GMJ summary
This introductory section of the MSF tuberculosis guideline defines the indications for treating rifampicin-susceptible and isoniazid-resistant tuberculosis (Hr-TB) in children and adults. Treatment is indicated when drug susceptibility testing (DST) confirms rifampicin susceptibility and isoniazid resistance, or when isoniazid resistance is strongly suspected (such as in household or close contacts of confirmed Hr-TB patients) whilst awaiting DST results or when isoniazid testing is unavailable.
The standard Hr-TB regimen should be used when susceptibility to fluoroquinolones is confirmed and, if possible, when susceptibility to pyrazinamide is also confirmed. Fluoroquinolone resistance can be detected simultaneously with isoniazid resistance using rapid molecular tests (Xpert MTB/XDR). Pyrazinamide resistance requires more complex testing that may not always be available at treatment initiation, and ethambutol susceptibility cannot be reliably confirmed by existing DST methods.
Alternative regimens should be considered for patients with additional drug resistance, contraindications or intolerance to fluoroquinolones and/or pyrazinamide. The guidance applies to both pulmonary and extrapulmonary tuberculosis.
Key points
For clinicians — doses and thresholds as stated in the guideline
- Hr-TB treatment is indicated when DST confirms rifampicin susceptibility and isoniazid resistance in children and adults with pulmonary or extrapulmonary TB
- Treatment may be initiated when isoniazid resistance is strongly suspected (e.g. household/close contacts of confirmed Hr-TB) whilst awaiting DST results or if testing is unavailable
- Standard Hr-TB regimen should be used when fluoroquinolone susceptibility is confirmed and, if possible, pyrazinamide susceptibility is also confirmed
- Xpert MTB/XDR rapid molecular test can detect fluoroquinolone resistance simultaneously with isoniazid resistance
- Pyrazinamide resistance detection requires complex tests (phenotypic DST or Genoscholar PZA-TB II) that may not be available at treatment start
- Ethambutol susceptibility cannot be reliably confirmed as no reliable DST exists
- Alternative regimens should be considered for patients with additional resistance, contraindications or intolerance to fluoroquinolones and/or pyrazinamide
From the guideline
Verbatim
“Patient with Hr-TB should be treated with the standard Hr-TB regimen when: Susceptibility to fluoroquinolones is confirmed and, if possible Susceptibility to pyrazinamide is confirmed.”
Editor’s perspective
Why this matters for Georgia and the region
Prof. Giorgi Pkhakadze, MD, MPH, PhD
Editor-in-Chief, Georgian Medical Journal · Chair, Public Health Institute of Georgia · WHO consultant, health and migration
As Editor-in-Chief of the Georgian Medical Journal and Chair of the Public Health Institute, I recognise that isoniazid-resistant tuberculosis represents a growing challenge in Georgia and across the Eastern European region, where TB transmission dynamics differ from Western settings. This MSF guidance provides a practical algorithmic approach that Georgian clinicians can implement immediately, particularly the emphasis on using Xpert MTB/XDR to simultaneously detect isoniazid and fluoroquinolone resistance, thereby avoiding delays in appropriate treatment initiation. The critical implementation challenge for Georgia will be ensuring that fluoroquinolone susceptibility testing is universally available before initiating the standard Hr-TB regimen, as empirical use without confirmed susceptibility risks amplifying resistance in a region already burdened by multidrug-resistant TB. Our national programme must prioritise strengthening laboratory networks to support both rapid molecular diagnostics and phenotypic DST for pyrazinamide, whilst developing clear protocols for managing patients where complete DST profiles remain unavailable.
ORCID 0000-0001-7609-4515 · Perspective written for the GMJ Guidelines Library, 23 Oct 2026
Applicability
Georgia and the South Caucasus
Georgia has a well-established national TB programme with DST capacity, making this guidance immediately applicable. The country reports moderate levels of isoniazid-resistant TB, and access to rapid molecular diagnostics including Xpert technology has expanded in recent years. National TB programmes in Georgia and neighbouring South Caucasus countries would need to ensure availability of fluoroquinolone susceptibility testing (ideally through Xpert MTB/XDR) to safely implement the standard Hr-TB regimen. Where pyrazinamide DST remains limited, programmes must balance the benefits of timely treatment initiation against the risks of undetected resistance, and strengthen laboratory networks to support phenotypic DST or molecular alternatives like Genoscholar PZA-TB II.
Questions this guideline answers
Quick answers
When should I start Hr-TB treatment if isoniazid DST results are pending?
Treatment can be initiated when rifampicin susceptibility is confirmed by DST and isoniazid resistance is strongly suspected, such as in household or close contacts of a confirmed Hr-TB patient, whilst awaiting DST results for isoniazid.
Is fluoroquinolone susceptibility testing mandatory before starting the standard Hr-TB regimen?
Yes, susceptibility to fluoroquinolones must be confirmed before using the standard Hr-TB regimen. This can be detected at the same time as isoniazid resistance using rapid molecular tests like Xpert MTB/XDR.
What if pyrazinamide DST is not available at my facility?
Pyrazinamide susceptibility confirmation is recommended 'if possible' but not absolutely required. However, pyrazinamide resistance requires more complex tests (phenotypic DST or Genoscholar PZA-TB II) that cannot always be performed or may not have results available at treatment start.
Can I use ethambutol susceptibility testing to guide Hr-TB treatment?
No, there is no reliable DST for ethambutol susceptibility, so this cannot be confirmed to guide treatment decisions.
Related on GMJ
Interconnected resources
Drugs A–Z
Quality & accreditation
- ASF Laboratory — Standard 1 — Governance & Document Control
- ASF Laboratory — Standard 6 — Pre-Examination: Specimen Pathway
- ASF Laboratory — Standard 7 — Examination: Process & Safety
- ASF Laboratory — Standard 8 — Post-Examination: Reporting & Critical Values
- ASF Hospital — Standard 13 — Radiology
- ASF Laboratory — Standard 4 — Equipment, Reagents & Traceability
Same guideline
- Surgery in Multidrug-Resistant and Rifampicin-Resistant Tuberculosis — MSF TuberculosisChapter 10: Treatment of multidrug-resistant and rifampicin-resistant tuberculosis
- Treatment interruptions — MSF TuberculosisChapter 10: Treatment of multidrug-resistant and rifampicin-resistant tuberculosis
- Treatment adaptation and change of treatment — MSF TuberculosisChapter 10: Treatment of multidrug-resistant and rifampicin-resistant tuberculosis
- Adverse effects — MSF TuberculosisChapter 10: Treatment of multidrug-resistant and rifampicin-resistant tuberculosis
- Patient Monitoring — Multidrug-Resistant and Rifampicin-Resistant Tuberculosis — MSF TuberculosisChapter 10: Treatment of multidrug-resistant and rifampicin-resistant tuberculosis
- Special situations in multidrug-resistant and rifampicin-resistant tuberculosis treatment — MSF TuberculosisChapter 10: Treatment of multidrug-resistant and rifampicin-resistant tuberculosis
Other guidelines on this topic
- Surgery in Multidrug-Resistant and Rifampicin-Resistant Tuberculosis — MSF Tuberculosis
- Treatment interruptions — MSF Tuberculosis
- Treatment adaptation and change of treatment — MSF Tuberculosis
- Adverse effects — MSF Tuberculosis
- Patient Monitoring — Multidrug-Resistant and Rifampicin-Resistant Tuberculosis — MSF Tuberculosis
- Issuer
- Médecins Sans Frontières
- Guideline
- Tuberculosis
- Chapter
- Chapter 11: Treatment of rifampicin-susceptible and isoniazid-resistant tuberculosis
- Type
- Clinical guideline (chapter)
- Edition
- Current online edition, 2026
- Status
- Current
- Published
- 2026-10-14
- Scope
- Children and adults with pulmonary and extrapulmonary rifampicin-susceptible, isoniazid-resistant tuberculosis
- Audience
- Clinicians treating tuberculosis in MSF field settings and similar resource-limited contexts
- Evidence
- Based on individual patient data meta-analysis and WHO operational handbook recommendations
- Record history
- Created 23 Oct 2026 · updated 23 Oct 2026 · next check Apr 2027
Médecins Sans Frontières. 11.1 Introduction. In: Tuberculosis [guideline]. Chapter 11: Treatment of rifampicin-susceptible and isoniazid-resistant tuberculosis. Paris: MSF; 2026 Oct 14.GMJ Guidelines Library records are original summaries written by the GMJ editorial team from the issuer’s published document and reviewed by a physician. They do not replace the full guideline. The document is the copyright of its issuer and is linked, not hosted. Spotted an error or a newer edition? Tell the Guidelines Desk.
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