From Tuberculosis › Chapter 11: Treatment of rifampicin-susceptible and isoniazid-resistant tuberculosis · Médecins Sans Frontières, Current online edition, 2026
MSF guidance on 6-month Hr-TB treatment with levofloxacin for clinicians managing drug-resistant tuberculosis.
- Issuer
- Médecins Sans Frontières
- Edition
- Current online edition, 2026
- Audience
- Clinicians treating tuberculosis
- Evidence
- Expert consensus
- Reviewed
- 23 Oct 2026 · GMJ
What this guideline says
GMJ summary
This section of the MSF tuberculosis guideline describes the standard treatment regimen for isoniazid-resistant tuberculosis (Hr-TB). The core recommendation is a 6-month regimen using the fixed-dose combination HRZE (isoniazid, rifampicin, pyrazinamide, ethambutol) plus levofloxacin throughout treatment, despite isoniazid resistance.
Although there is no evidence for the benefit of continuing isoniazid when resistance is present, the HRZE combination is used for patient convenience because no RZE fixed-dose combination is currently available. Levofloxacin is preferred over moxifloxacin due to its better safety profile and because rifampicin reduces moxifloxacin plasma concentrations. Treatment prolongation may be considered for patients with lung cavities or positive sputum smear at the end of Month 2, but only after ruling out resistance to rifampicin, fluoroquinolones, and pyrazinamide.
If isoniazid resistance is detected after starting drug-susceptible TB treatment, a new rapid molecular test should confirm rifampicin susceptibility before switching to the full 6-month Hr-TB regimen.
Key points
For clinicians — doses and thresholds as stated in the guideline
- Standard Hr-TB regimen: 6 months of HRZE plus levofloxacin throughout treatment (6(HRZE)-Lfx)
- HRZE dosed as per intensive phase of drug-susceptible TB treatment
- In children weighing less than 23 kg, give ethambutol with HRZ fixed-dose combination
- Levofloxacin is preferred over moxifloxacin (better safety profile; rifampicin reduces moxifloxacin plasma concentration)
- Treatment prolongation considered case-by-case for lung cavities or sputum smear-positive at end of Month 2
- Before prolonging treatment, rule out resistance to rifampicin, fluoroquinolones, and (if possible) pyrazinamide
- If Hr-TB detected during DS-TB treatment: perform new rapid molecular test to confirm rifampicin susceptibility, then switch to full 6-month Hr-TB regimen
From the guideline
Verbatim
“Levofloxacin is preferred over moxifloxacin in the standard Hr-TB regimen (better safety profile).”
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 Georgia continues to strengthen its drug-resistant tuberculosis programme, this MSF guidance on isoniazid-resistant TB fills an important practical gap. The recommendation to use levofloxacin rather than moxifloxacin is particularly relevant for our national formulary decisions, given the drug interaction with rifampicin. I would stress to Georgian clinicians the critical step of performing a new rapid molecular test to confirm rifampicin susceptibility before switching any patient from DS-TB to Hr-TB treatment—this prevents inadvertently treating multidrug-resistant TB with an inadequate regimen. The main implementation challenge will be ensuring uninterrupted supply of levofloxacin alongside the standard fixed-dose combinations, particularly in regional centres outside Tbilisi where supply chains can be less reliable.
ORCID 0000-0001-7609-4515 · Perspective written for the GMJ Guidelines Library, 23 Oct 2026
Applicability
Georgia and the South Caucasus
Isoniazid-resistant tuberculosis represents a significant proportion of drug-resistant TB in Georgia and the South Caucasus region. National TB programmes in the region should ensure availability of levofloxacin alongside standard fixed-dose combinations, establish clear protocols for switching from DS-TB to Hr-TB regimens when isoniazid resistance is detected, and ensure rapid molecular testing capacity to confirm rifampicin susceptibility before treatment changes. The preference for levofloxacin over moxifloxacin has practical supply chain implications for national essential medicines lists. Programmes must also address the challenge that no RZE fixed-dose combination exists, requiring continued use of HRZE despite isoniazid resistance.
Questions this guideline answers
Quick answers
Why continue isoniazid if the patient has Hr-TB?
Although there is no evidence of benefit from taking isoniazid despite resistance, the HRZE fixed-dose combination is used for patient convenience because no RZE fixed-dose combination is currently available.
Why is levofloxacin preferred over moxifloxacin for Hr-TB?
Levofloxacin has a better safety profile than moxifloxacin. Additionally, rifampicin reduces the plasma concentration of moxifloxacin, which could compromise treatment effectiveness.
When should treatment be prolonged beyond 6 months?
Treatment prolongation may be considered case-by-case for patients with lung cavities or sputum smear still positive after Month 2. However, resistance to rifampicin, fluoroquinolones, and (if possible) pyrazinamide must first be ruled out.
What if isoniazid resistance is detected after starting DS-TB treatment?
Perform a new rapid molecular test to rule out rifampicin resistance. Once rifampicin susceptibility is confirmed, change to the full 6-month standard Hr-TB regimen.
Related on GMJ
Interconnected resources
Dictionary of Public Health
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 4 — Care & Treatment
- ASF Hospital — Standard 7 — Governance & Management
Same guideline
- Treatment of rifampicin-susceptible and isoniazid-resistant tuberculosis — Introduction — MSF TuberculosisChapter 11: Treatment of rifampicin-susceptible and isoniazid-resistant tuberculosis
- 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
Other guidelines on this topic
- Treatment of rifampicin-susceptible and isoniazid-resistant tuberculosis — Introduction — MSF Tuberculosis
- 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
- 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
- Isoniazid-resistant tuberculosis
- Audience
- Clinicians treating tuberculosis
- Evidence
- Expert consensus
- Record history
- Created 23 Oct 2026 · updated 23 Oct 2026 · next check Apr 2027
Médecins Sans Frontières. Standard treatment regimen. In: Tuberculosis. Chapter 11: Treatment of rifampicin-susceptible and isoniazid-resistant tuberculosis, section 11.2. 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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