Drugs for drug-resistant tuberculosis — MSF Tuberculosis — Médecins Sans Frontières 2026

MSFClinical guideline (chapter)Current edition

From Tuberculosis › Chapter 8: Tuberculosis drugs and treatment regimens · Médecins Sans Frontières, Current online edition

MSF guidance on selection, use and toxicity management of second-line TB drugs for clinicians treating drug-resistant tuberculosis.

In one sentenceDR-TB drugs are organised into Groups A–C; bedaquiline has 5.5-month half-life requiring CYP450 interaction management; give pyridoxine with linezolid, cycloserine and high-dose isoniazid; avoid aminoglycosides unless essential with close monitoring.

Issuer: Médecins Sans Frontières
Edition: Current online edition
Audience: Clinicians treating drug-resistant tuberculosis
Evidence: Expert consensus with cited evidence
Reviewed: 22 Oct 2026 · GMJ

Read the original on MSF Whole guideline (PDF)

Summary by GMJ Guidelines Desk•Reviewed by Prof. Giorgi Pkhakadze, MD, MPH, PhD•Record updated 22 Oct 2026•Next check Apr 2027

What this guideline says

GMJ summary

This section of the MSF Tuberculosis guideline provides comprehensive guidance on drugs used to treat drug-resistant tuberculosis (DR-TB), organised into Groups A, B, and C according to the WHO classification. Group A drugs (fluoroquinolones, bedaquiline, linezolid) form the backbone of DR-TB treatment due to their bactericidal activity, whilst Group B drugs (clofazimine, cycloserine/terizidone) and Group C drugs (delamanid, ethambutol, pyrazinamide, carbapenems, aminoglycosides, thionamides, PAS, high-dose isoniazid) provide additional options based on resistance patterns and tolerability.

The guideline emphasises that most DR-TB drugs are taken 7 days a week (except bedaquiline) and highlights critical safety considerations including QT prolongation risks, myelosuppression, neuropathy, and hepatotoxicity. Special attention is given to drug interactions, particularly bedaquiline’s metabolism via CYP450 enzymes, and cross-resistance patterns between drug classes. The guidance notes that aminoglycosides should only be used when no alternative is available, and that kanamycin and capreomycin are no longer recommended due to association with higher treatment failure and death rates.

Specific monitoring requirements are detailed for high-risk drugs, including vision monitoring for ethambutol beyond 2 months, audiometry and renal function for aminoglycosides, and pyridoxine (vitamin B6) supplementation for linezolid, cycloserine/terizidone, and high-dose isoniazid to prevent neuropathy. The guideline also addresses newer regimens containing pretomanid (BPaLM, BPaL, BPaLC) and the essential co-administration of amoxicillin/clavulanic acid with carbapenems.

Key points

For clinicians — doses and thresholds as stated in the guideline

Bedaquiline has a very long half-life (5.5 months) meaning adverse effects can persist after stopping and resistance can develop if TB remains active; avoid drugs that induce or inhibit CYP450 enzymes
Clofazimine has a half-life of approximately 70 days, causing skin discolouration in almost all patients (reversible and not harmful) and prolonged adverse effects after discontinuation
Pyridoxine (vitamin B6) should be given to all patients on linezolid (although no evidence it prevents neuropathy), cycloserine/terizidone, and high-dose isoniazid throughout treatment to prevent neurotoxicity
Aminoglycosides (amikacin, streptomycin) should only be used when no alternative is available, with close monitoring essential (audiometry, electrolytes, renal function); if monitoring cannot be ensured, do not use
Meropenem should be used rather than imipenem/cilastatin in children and adolescents under 15 years and in patients with epilepsy or TB meningitis due to lower seizure risk
Vision monitoring is required when ethambutol is administered for more than 2 months due to risk of optic neuritis
Ethambutol resistance prevalence is >49% among MDR/RR-TB patients in some settings; pyrazinamide resistance is >80% in some areas
Amoxicillin/clavulanic acid must be administered before each carbapenem dose; only use formulations with ratio 4:1 (e.g. 500/125 mg) or 2:1 (e.g. 250/125 mg), not 8:1 or 7:1

Main characteristics of TB drugs Group A

Table extracted from the guideline

TB drugs	Classes	Activity	Resistance
Levofloxacin, Moxifloxacin	Fluoroquinolones (FQs)	Bactericidal	Resistance common in some regions. Cross-resistance between FQs.
Bedaquiline	Diarylquinolines	Bactericidal	Partial cross-resistance with Cfz. Growing resistance as use increases.
Linezolid	Oxazolidinones	Bactericidal	Resistance assumed to be rare due to its limited use.

Source: Médecins Sans Frontières, Drugs for drug-resistant tuberculosis — MSF Tuberculosis. Reproduced in summary form.

From the guideline

Verbatim

“Aminoglycosides should only be used when no alternative is available. Most patients with DR-TB can be treated without aminoglycosides, including some cases of extensively drug-resistant TB (XDR-TB).”

— Médecins Sans Frontières, Drugs for drug-resistant tuberculosis — MSF Tuberculosis, Section 8.4.3, Group C drugs, Aminoglycosides (2026)

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 we continue to strengthen tuberculosis control in Georgia and across the South Caucasus, this MSF guidance on second-line TB drugs is particularly timely given the complexity of managing drug-resistant cases in our region. The pharmacokinetic details are critical: bedaquiline's 5.5-month half-life and clofazimine's 70-day half-life mean that adverse effects persist long after discontinuation and require sustained vigilance, whilst the clear instruction to avoid CYP450-interacting drugs with bedaquiline prevents potentially dangerous plasma concentration changes. I would stress to Georgian clinicians the explicit guidance that aminoglycosides should only be used when no alternative exists—most DR-TB patients, including some XDR-TB cases, can be treated without them—which aligns with our goal of reducing ototoxicity and nephrotoxicity in our patient population. The main implementation challenge for our national TB programme will be ensuring consistent access to audiometry, renal function monitoring, and ECG facilities across all treatment sites, particularly in rural areas, as the guideline makes clear that if close monitoring cannot be ensured, certain drugs simply should not be used.

ORCID 0000-0001-7609-4515 · Perspective written for the GMJ Guidelines Library, 22 Oct 2026

Applicability

Georgia and the South Caucasus

Drug-resistant tuberculosis remains a significant challenge in Georgia and the South Caucasus, where resistance patterns vary by region and previous treatment exposure. National TB programmes must consider local resistance surveillance data when selecting second-line drugs, particularly given the documented regional variation in fluoroquinolone resistance and the high prevalence of ethambutol (>49% in some settings) and pyrazinamide resistance (>80% in some areas) among MDR/RR-TB patients. The emphasis on avoiding aminoglycosides unless essential is particularly relevant for settings with limited capacity for audiometry and regular renal function monitoring. Programmes introducing newer agents like bedaquiline and delamanid must establish robust pharmacovigilance systems for QT monitoring and manage the procurement challenges and drug interactions associated with complex regimens, whilst ensuring access to pyridoxine supplementation for neuropathy prevention across all treatment sites.

Questions this guideline answers

Quick answers

Why is pyridoxine recommended with linezolid if there's no evidence it prevents neuropathy?

Pyridoxine (vitamin B6) supplementation is recommended for all patients on linezolid as a precautionary measure, although the guideline explicitly states there is no evidence that pyridoxine can prevent linezolid-induced neuropathy. It is also essential for patients on cycloserine/terizidone and high-dose isoniazid, where it does help prevent neurotoxicity.

Can bedaquiline and clofazimine be used together despite cross-resistance concerns?

The guideline notes that bedaquiline and clofazimine have partial cross-resistance, and the extent and clinical implications are not fully understood. Both drugs show growing resistance as use increases. Clinical decisions should be guided by resistance testing when available and consideration of alternative regimen options.

What formulation of amoxicillin/clavulanic acid should be used with carbapenems?

Only formulations with a ratio of 4:1 (e.g. 500/125 mg) or 2:1 (e.g. 250/125 mg) are suitable. Do not use formulations with a ratio of 8:1 or 7:1. The clavulanic acid component prevents the development of carbapenem resistance and must be given before each carbapenem dose.

When should meropenem be preferred over imipenem/cilastatin?

Meropenem should be used in children and adolescents under 15 years, and if possible in patients with epilepsy or TB meningitis, because the risk of seizures is lower than with imipenem/cilastatin. Meropenem does not need to be combined with cilastatin as it is metabolised through a different pathway.

Related on GMJ

Interconnected resources

Dictionary of Public Health

Drug-resistant tuberculosis

Drugs A–Z

Quality & accreditation

Same guideline

Tuberculosis drug formulations — MSF TuberculosisChapter 8: Tuberculosis drugs and treatment regimens
Drugs for drug-susceptible tuberculosis — MSF TuberculosisChapter 8: Tuberculosis drugs and treatment regimens
Standard code for treatment regimens — MSF TuberculosisChapter 8: Tuberculosis drugs and treatment regimens
Drug Susceptibility Pattern — Tuberculosis — MSF TuberculosisChapter 7: Case definitions
Bacteriological status — MSF TuberculosisChapter 7: Case definitions
High-risk groups — MSF TuberculosisChapter 6: Screening for active tuberculosis

Drugs for drug-resistant tuberculosis — MSF Tuberculosis

What this guideline says

Key points

Main characteristics of TB drugs Group A

From the guideline