China's 2026 guideline on off-label anti-tuberculosis drug use gives 25 recommendations for 13 drugs. It tells clinicians when bedaquiline may continue beyond 24 weeks, when delamanid must not be started, and why every carbapenem dose needs clavulanic acid. This article translates the recommendations into practical checks for wards and pharmacies.

What off-label anti-tuberculosis drug use means under the 2026 guideline

Off-label anti-tuberculosis drug use means giving a tuberculosis drug in a way its label does not approve: a higher dose, a longer course, a new patient group, or a different route such as inhalation or injection. In tuberculosis care, off-label anti-tuberculosis drug use is not exceptional. Newer drugs such as bedaquiline, delamanid, and contezolid, and all-oral short regimens, reach treatment guidelines faster than drug labels are revised. The result is a clear gap: the guideline tells the clinician to use a drug one way, and the label says something else or nothing at all.

The 2026 document upgrades the 2023 expert consensus into a formal clinical guideline. It was issued by the tuberculosis society of a national medical association and published in a national tuberculosis and respiratory journal in September 2026, volume 49 issue 9, pages 924 to 944. It covers 13 drugs and issues 25 recommendations, graded with the GRADE system, reported under the RIGHT standard, and registered as PREPARE-2025CN682. Fourteen recommendations are strong and eleven are weak. No recommendation rests on Grade A evidence: nineteen are Grade B, three are Grade C, and three are Grade D. That is an honest picture of current research, not a defect, and clinicians should use it with clear expectations. The guideline plans to update its recommendations every three to five years.

Why this guideline matters now

Tuberculosis remains a major global public health problem. The United Nations health agency's 2025 global tuberculosis report estimates about 10.7 million new patients and about 1.23 million deaths in 2024. China is a dual high-burden country for tuberculosis and multidrug resistant tuberculosis, including rifampicin resistant tuberculosis.

The underlying contradiction is simple. Newer drugs and all-oral short regimens are recommended by international and national guidance faster than labels can be revised. Complex resistant disease, drug intolerance, and treatment in special populations have made off-label anti-tuberculosis drug use routine practice, yet for a long time there was no unified evidence base or monitoring standard. This guideline closes that middle ground.

The legal frame: three conditions that make off-label use lawful

Off-label use is not "do whatever is necessary and take the consequences." Article 29 of the Physician Law of China, effective since March 1, 2022, gives it a defined legal place with three paragraphs that must be read together.

Paragraph one states the principle: doctors must follow safe, effective, and economical prescribing principles and adhere to clinical drug-use principles, diagnosis and treatment guidelines, and drug labels.

Paragraph two is the exception channel: where no effective or better treatment exists, a doctor may use a drug in a way not specified in the label, after obtaining the patient's explicit informed consent, provided the use is supported by clinical evidence.

Paragraph three is the institutional responsibility: medical institutions must establish management systems to review the appropriateness of doctors' prescriptions and medication orders.

The three conditions below must all be met; missing one makes the use unlawful.

Condition	What it requires
Clinical necessity	No effective or better treatment exists, and no reasonable substitute drug is available
Evidence-based support	Supported by guidelines, consensus documents, systematic reviews, randomized trials, or meta-analyses; not for experimental purposes
Informed consent	The patient or legal guardian signs written confirmation after being told about the unapproved use and its risks
Institutional review	The hospital's review or argumentation process is completed

The guideline adds five basic principles: sufficient clinical evidence; benefits fully assessed against risks with expected benefit greater than risk and no suitable substitute; argumentation completed with informed consent from the patient or legal guardian; a standardized safety monitoring system established; and the benefit-risk balance assessed regularly.

Its clinical significance falls into four points: supplementing treatment options when standard regimens fail in resistant, severe, extrapulmonary, or hard-to-treat disease; optimizing regimens through broader drug choices and better drug exposure, which may bring better bacteriological or clinical outcomes and shorter courses for some patients; meeting special population needs in liver or kidney impairment, children, older adults, and pregnant or breastfeeding women; and supporting complex case decisions involving comorbidities, important drug interactions, serious adverse reactions, or special lesion sites.

Safety monitoring: baseline, dynamic, and graded response

Recommendation 2 carries unusual weight: off-label use must be backed by an individualized drug safety monitoring plan, built around the toxicity of each drug, the patient's own situation, and drug interactions (strong recommendation, moderate evidence). Monitoring is not one fixed schedule for all drugs; frequency is set by drug toxicity, treatment stage, baseline risk, concomitant drugs, and prior results, and intervals must be shortened after abnormal results, dose adjustments, or high-risk combinations.

Layer	When	What to check
Baseline	Before starting	Blood count, liver and kidney function, ECG, hearing and vision, medical history; add serum potassium, serum albumin, or blood lactate as needed
Dynamic	During treatment	Frequency set by drug toxicity, treatment stage, baseline risk, concomitant drugs, and prior results; shorten intervals after abnormal results, dose changes, or high-risk drug combinations
Graded response	When adverse reactions appear	Mild: observe closely and increase monitoring frequency; moderate: consider dose reduction or pause and adjust the regimen; severe: stop the drug, give appropriate treatment, and hospitalize if necessary

Special populations each have their own calculus: children need dose adjustment by weight and attention to growth and development; older adults need cognitive checks and vigilance against drug accumulation; patients with liver or kidney impairment need dose and monitoring adjustments based on test results; pregnant women need individualized regimen choice based on disease severity, pregnancy safety data, and mother-fetus benefit-risk assessment, with stronger obstetric and fetal monitoring.

Therapeutic drug monitoring (TDM) is indicated for toxicity, poor treatment response, special populations, and long courses beyond six months. The guideline's wording is "TDM where conditions allow": it is not mandatory for everyone, but once one of these four situations appears, not doing it is hard to justify.

Therapeutic drug monitoring: when it is needed and what the numbers mean

The guideline gives empirical reference ranges only, and explicitly states they are not fixed treatment targets. Dosing should never be forced into these ranges; results must be read together with dose, sampling time, treatment response, and adverse reactions.

For fluoroquinolones, the levofloxacin Cmax reference is 8 to 12 mg per liter, and the moxifloxacin Cmax reference is 3 to 5 mg per liter. For linezolid, the trough concentration reference is 2 to 8 mg per liter, and a higher trough is linked with higher blood and mitochondrial toxicity risk.

Thirteen drugs and twenty five recommendations: the full map

The table below condenses the 25 recommendations of off-label anti-tuberculosis drug use by drug. The number and letter after each recommendation in the source show its strength (1 strong, 2 weak) and evidence quality (A to B in this guideline; none reaches A). Specific doses, frequencies, courses, and child weight bands should be checked against the original text.

Drug	Main off-label uses in the guideline	Key dose or threshold	Monitoring focus
Isoniazid	Low-level resistance; tuberculosis meningitis intensification; inhalation, injection, or cavity instillation	Adults 10 to 15 mg/kg once daily; children 15 to 20 mg/kg once daily; not counted as a core effective drug	Liver function, neurotoxicity, vitamin B6, TDM with NAT2 acetylation phenotype
Rifampicin	Preventive treatment 3HR and 4R; tuberculosis meningitis high dose; pregnancy	3HR for 3 months; 4R for 4 months; 15 to 35 mg/kg not routine	Liver function, drug interactions, pregnancy safety monitoring
Rifapentine	Preventive treatment 3H2P2	Isoniazid 500 to 600 mg per dose, rifapentine 450 to 600 mg per dose, twice weekly, 3 months	Liver function, adherence, adverse reactions
Levofloxacin	Multidrug resistant and rifampicin resistant TB regimens; rifampicin-sensitive isoniazid-resistant TB; drug-sensitive TB when first-line drugs are unusable; children; close contact prevention 6Lfx	6Lfx: 6 months, once daily; Cmax reference 8 to 12 mg per liter	QTcF, electrolytes, tendon and nervous system reactions, TDM
Moxifloxacin	Multidrug resistant TB without fluoroquinolone resistance; resistant tuberculosis meningitis individualized	800 mg per day not routine; Cmax reference 3 to 5 mg per liter	ECG and serum electrolytes; TDM
Linezolid	Multidrug resistant TB including pre-extensively drug resistant and extensively drug resistant TB; resistant or difficult tuberculosis meningitis; non-severe extrapulmonary multidrug resistant TB	Adults usually 600 mg once daily; trough reference 2 to 8 mg per liter	Blood count, optic and peripheral neuropathy, lactic acidosis; avoid serotonergic drugs
contezolid	Linezolid intolerance or high toxicity risk when the regimen needs an oxazolidinone	Considered after assessment; weak recommendation, low evidence	Safety profile of the substitute; record assessment and informed consent
Clofazimine	All tuberculosis use is off-label; long regimen group B drug; some six-month and nine-month regimens	Adults 100 mg once daily with food; children 2 to 5 mg per kg per dose once daily, maximum 100 mg per day	Skin and mucosa pigmentation, QTcF; more ECG when combined with QT-prolonging drugs
Bedaquiline	Adult rifampicin resistant TB; children of any age; beyond 24 weeks; pregnancy; extrapulmonary multidrug resistant TB	Beyond 24 weeks follows the regimen	QTcF, liver function; closer ECG monitoring in older adults, heart disease, electrolyte disturbance, or combined QT-prolonging drugs
Delamanid	Adult rifampicin resistant TB; children of any age; beyond 24 weeks; pregnancy; extrapulmonary multidrug resistant TB	Serum albumin below 28 g per liter: do not use	QTcF, serum electrolytes, serum albumin
Amikacin	When an effective all-oral or standard regimen cannot be composed; severe or difficult tuberculosis meningitis intensification	Adjust by creatinine clearance or extend the dosing interval	Serum creatinine, urinalysis, hearing and vestibular function; TDM if available
Meropenem	When groups A and B drugs cannot compose an effective regimen; group C drug for long courses	Every dose with clavulanic acid	Nervous system reactions including seizure risk, kidney function
Imipenem/cilastatin	Same as meropenem	Every dose with clavulanic acid	Nervous system reactions, kidney function

First-line drugs: isoniazid and rifamycins

The standard approved adult dose of isoniazid is 5 mg per kg once daily, up to 300 mg per day. Doses of 10 to 15 mg per kg, and routes such as inhalation, intrathecal injection, or injection into body cavities, are off-label. Recommendation 3 supports high-dose isoniazid for patients with low-level resistance and as part of certain short multidrug resistant regimens, but it must not be counted as a core effective drug. Recommendation 4 sets the condition: low-level resistance plus evidence that isoniazid may still work, judged from the resistance genotype combined with phenotype or minimum inhibitory concentration testing. Specifically, an inhA-related mutation without a high-level katG mutation suggests residual activity. Adults may use 10 to 15 mg per kg once daily; children and adolescents may use 15 to 20 mg per kg once daily, with the course set by the full regimen. Add vitamin B6 routinely, strengthen liver and neurotoxicity monitoring, and use TDM where available, with the NAT2 acetylation phenotype to help individualize the dose. Recommendation 5 allows local administration such as inhalation, bronchial instillation, intrathecal injection, or pleural, peritoneal, joint, or lymph node injection for specific situations, but only as an adjunct to systemic treatment and only with weak, low-grade evidence.

For rifamycins, recommendation 7 covers preventive treatment: three months of isoniazid plus rifampicin (3HR, strong, moderate evidence) or four months of rifampicin alone (4R, weak, moderate evidence). Part of tuberculosis meningitis patients may receive individualized higher rifampicin doses in the intensification phase, but routine use is not recommended (weak, low evidence). High-dose rifampicin at 15 to 35 mg per kg has mainly research value for dose optimization and course shortening in drug-sensitive tuberculosis, and routine use is not recommended. Local routes are adjunct only. Pregnant patients with drug-sensitive tuberculosis may use rifampicin based on benefit-risk assessment, including in the first trimester, with strengthened safety monitoring.

Recommendation 8 is the 3H2P2 preventive regimen: isoniazid 500 to 600 mg per dose and rifapentine 450 to 600 mg per dose, twice weekly, for three months. Based on Chinese population pharmacokinetics and safety data, this is the strongest evidence recommendation in the guideline and the most specific to China (strong, moderate evidence).

Fluoroquinolones: levofloxacin and moxifloxacin

The guideline sorts fluoroquinolone use into three tiers by patient type, and the tier matters more than the dose. For fluoroquinolone-sensitive multidrug resistant and rifampicin resistant tuberculosis, these drugs are key parts of several short and longer regimens (strong, moderate evidence). For rifampicin-sensitive isoniazid-resistant tuberculosis, they may be part of recommended regimens after excluding fluoroquinolone resistance (weak, low evidence). For drug-sensitive tuberculosis, they are individualized substitutes only when first-line drugs cannot be used because of severe adverse reactions or contraindications (weak, moderate evidence).

Recommendation 10 allows levofloxacin for children of any age with multidrug resistant and rifampicin resistant tuberculosis, with doses stratified by age and weight (weak, moderate evidence). Recommendation 11 recommends six months of daily levofloxacin (6Lfx) for eligible close contacts of multidrug resistant and rifampicin resistant tuberculosis patients, after excluding active tuberculosis and weighing the source case's drug sensitivity, contact risk, and contraindications (strong, moderate evidence). Recommendation 12 allows moxifloxacin for multidrug resistant tuberculosis without fluoroquinolone resistance, and individualized use in resistant tuberculosis meningitis, but 800 mg per day is not for routine use (strong, moderate evidence; 800 mg per day weak, low evidence). Long-term, high-dose use, or combination with other QT-prolonging drugs, calls for ECG and serum electrolyte monitoring (strong, low evidence).

Recommendation 13 gives the TDM references above: levofloxacin Cmax 8 to 12 mg per liter and moxifloxacin Cmax 3 to 5 mg per liter, as empirical references not fixed targets.

Oxazolidinones: linezolid and contezolid

Linezolid is a backbone of resistant tuberculosis regimens and a major source of adverse reactions. Recommendation 14 covers multidrug resistant tuberculosis including pre-extensively drug resistant and extensively drug resistant tuberculosis, resistant or difficult tuberculosis meningitis, and non-severe extrapulmonary multidrug resistant tuberculosis, for adults and children (strong, moderate evidence). Adults usually take 600 mg once daily; children are dosed by age and weight; the course follows the combination regimen. Recommendation 15 requires monitoring for bone marrow suppression, optic neuropathy, peripheral neuropathy, and lactic acidosis during long treatment, with regular blood counts and vision and nerve symptom checks, plus blood lactate and acid-base status when necessary (strong, moderate evidence). Avoid combining with serotonergic drugs; if combination is unavoidable, strengthen monitoring.

Recommendation 16 supports therapeutic drug monitoring for long courses, especially when response is poor, serious adverse reactions occur, organs are damaged, body weight is extreme, or important interactions exist. Trough concentration, area under curve, and area-under-curve-to-MIC ratios are auxiliary exposure indicators; the 2 to 8 mg per liter trough range is an empirical reference only, not a fixed treatment window (weak, moderate evidence).

Recommendation 17 is new in 2026. For patients who cannot tolerate linezolid, or who are expected to tolerate it poorly because of baseline bone marrow suppression, nervous system disease, or other high toxicity risk, yet whose regimen needs an oxazolidinone to be effective, contezolid may be considered after assessment (weak, low evidence). The three qualifiers matter: cannot tolerate, the regimen needs it, and assessment first. It is not a switch to make casually.

Clofazimine: off label by default

Every use of clofazimine in tuberculosis is off-label. Recommendation 18 defines it as a group B drug in long multidrug resistant tuberculosis regimens and a component of some six-month and nine-month regimens, with the course set by the full regimen (strong, moderate evidence). Adults take 100 mg once daily with food. Children take 2 to 5 mg per kg per dose once daily, up to 100 mg per day, and soft capsules must not be opened to divide doses. Use with caution and stronger monitoring in severe liver impairment.

Recommendation 19 focuses on skin and mucosa pigmentation and QTcF changes, with baseline and during-treatment ECG checks, and more frequent ECG monitoring when combined with other QT-prolonging drugs (strong, moderate evidence). Skin and mucosa pigmentation is a common characteristic adverse reaction; it fades gradually after stopping but may take months or longer. This must be told to patients before treatment starts, or adherence will suffer.

Bedaquiline and delamanid: beyond 24 weeks and the albumin limit

The two drugs share five off-label situations in the guideline: adult rifampicin resistant tuberculosis, children of any age with multidrug resistant and rifampicin resistant tuberculosis, use beyond 24 weeks, pregnancy after benefit-risk assessment, and extrapulmonary multidrug resistant tuberculosis (non-severe cases follow short regimens; severe or complex cases use individualized long regimens).

Recommendation 21 requires monitoring QTcF prolongation and liver function abnormality during bedaquiline treatment, plus other drug-related adverse reactions (strong, moderate evidence). Older adults, patients with baseline heart disease or electrolyte disturbance, and those combined with clofazimine, fluoroquinolones, or delamanid need stronger ECG monitoring. The national chemotherapy guideline for multidrug resistant and rifampicin resistant tuberculosis (2026 edition) adds a practical threshold: correct abnormal blood potassium and magnesium before starting, and maintain serum potassium at 4.0 to 5.0 mmol/L during treatment.

Recommendation 22 sets a hard stop for delamanid: serum albumin below 28 g per liter means it must not be used, with no room for individualization (strong, moderate evidence). Monitor QTcF, serum electrolytes, and serum albumin before and during treatment. The same albumin threshold appears in the national 2026 chemotherapy guideline as a reason to withhold delamanid.

Injectables and carbapenems: amikacin and carbapenems with clavulanic acid

Recommendation 23 allows individualized amikacin use for multidrug resistant and rifampicin resistant tuberculosis, some retreated tuberculosis, and regimen changes because of intolerance, when an effective all-oral or standard regimen cannot be composed and drug sensitivity supports it; severe, difficult, or resistant tuberculosis meningitis may use it in the intensification phase (weak, low evidence). Local administration is adjunct only (weak, low evidence).

Recommendation 24 requires monitoring serum creatinine, urinalysis, hearing, and vestibular function (strong, moderate evidence). Adjust dose or extend the interval by creatinine clearance in kidney impairment. Use therapeutic drug monitoring where available, especially for kidney impairment, older patients, longer courses, or toxicity signs, and individualize by sensitivity, response, and adverse reactions.

Recommendation 25 covers carbapenems: when groups A and B drugs cannot compose an effective regimen, meropenem or imipenem/cilastatin plus clavulanic acid can serve as a group C drug in long multidrug resistant tuberculosis regimens (weak, low evidence). For resistant, severe, or difficult tuberculosis meningitis, use only when no other effective option exists; children and seizure-risk patients usually take meropenem first. The critical sentence: every dose of a carbapenem must be combined with clavulanic acid. Clavulanic acid inhibits the BlaC enzyme of tuberculosis bacteria; without this step, the value of carbapenems in an anti-tuberculosis regimen is sharply reduced. This is the step most easily missed in real practice.

Five mistakes to avoid

1. Treating a guideline recommendation of off-label anti-tuberculosis drug use as if the label already approved it. A recommended use is not necessarily on the label; charts, prescriptions, and consent forms must state the off-label use and its evidence base, or the duty to inform will be hard to prove in a dispute.

1. Starting delamanid without checking serum albumin. Below 28 g per liter is a hard contraindication, and albumin is a baseline item that must be checked in advance in malnourished, liver disease, or critically ill patients.

1. Giving carbapenems without clavulanic acid. Every dose must be combined; this is a precondition for the regimen, not an optional add-on.

1. Using high-dose rifampicin at 15 to 35 mg per kg as routine practice. The guideline assigns it research value only and recommends against routine use, including for tuberculosis meningitis intensification.

1. Treating TDM reference ranges as treatment targets. The levofloxacin, moxifloxacin, and linezolid references are empirical ranges, explicitly not fixed windows or goals.

Three teaching cases

The cases below are teaching illustrations of decision paths, not real patient information. Always adapt to the individual patient and follow your institution's rules.

Case 1: low-level isoniazid-resistant multidrug resistant and rifampicin resistant tuberculosis. Can the isoniazid dose be increased? The patient has an inhA-related mutation, no high-level katG mutation, and phenotypic low-level resistance, and the regimen needs another effective drug. This meets recommendations 3 and 4: use 10 to 15 mg per kg once daily within an effective combination regimen, with the course set by the full regimen. High-dose isoniazid is part of the regimen but not counted as a core effective drug. Add vitamin B6, strengthen liver and neurotoxicity monitoring, use TDM where available, and consider the NAT2 acetylation phenotype for dose individualization. Complete the institutional review and informed consent process.

Case 2: linezolid bone marrow suppression. The regimen must keep an oxazolidinone; who replaces linezolid? A patient on long multidrug resistant tuberculosis treatment takes linezolid 600 mg once daily and reaches month 8 with platelets down to 60 billion per liter and blood-count evidence of bone marrow suppression. Per recommendation 15, reduce, pause, or stop according to severity, and evaluate vision, nerve symptoms, blood lactate, and acid-base status as needed. If the patient truly cannot tolerate linezolid and the regimen needs an oxazolidinone, recommendation 17 allows considering contezolid after assessment. This is a weak, low-evidence recommendation: a considered option, not a first choice. The reason for switching, the assessment, and informed consent belong in the chart.

Case 3: a household close contact of a multidrug resistant and rifampicin resistant tuberculosis patient. Is preventive treatment needed? An adult contact has no evidence of active tuberculosis and no contraindication. Recommendation 11 recommends six months of daily levofloxacin (6Lfx) after excluding active disease, combining the source case's drug sensitivity, the contact's individual risk, and contraindications. The precondition is that the index patient's drug sensitivity supports the regimen; if the source is resistant to fluoroquinolones, the regimen must be redesigned. Pair the treatment with adherence support and monitoring of adverse reactions and tuberculosis symptoms.

One page cheat sheet

Red line	Threshold
Delamanid	Serum albumin below 28 g per liter: do not start
Carbapenems	Every dose combined with clavulanic acid
Bedaquiline-containing regimens	Maintain serum potassium at 4.0 to 5.0 mmol/L

Print this table and post it in the doctors' office. It condenses the recommendation table above; doses, frequencies, courses, and child bands should still be verified against the original guideline text.

From guideline to ward: seven steps for the department

1. Review current charts for off-label anti-tuberculosis drug use, and check each one against the guideline: is it recommended, and what are the strength and evidence grade?

1. Check whether the hospital has an off-label use management system: who accepts applications, who approves, and what is the re-review cycle? If none exists, have the pharmacy department lead the drafting.

1. Update the informed consent form template. It must cover at least four points: why this use (no substitute, benefit greater than risk), that the use is not approved on the label, possible unknown risks and adverse reactions, and the expected effect.

1. Package the baseline assessment as a standard set: blood count, liver and kidney function, ECG, hearing and vision, and history; add serum potassium, serum albumin, and blood lactate as needed.

1. Set the hospital's red-line thresholds: delamanid with serum albumin below 28 g per liter is not used; every carbapenem dose comes with clavulanic acid; bedaquiline-containing regimens maintain serum potassium at 4.0 to 5.0 mmol per liter.

1. Define the therapeutic drug monitoring sampling path: what can be tested in-house, where are the rest sent, and who interprets the results? Writing the process down works better than repeatedly debating whether to test.

1. Hold a department learning session. Focus on four items: the three paragraphs of Physician Law Article 29, the five basic principles, the procedures required before treatment, and the red-line thresholds in the cheat sheet.

Limitations

The guideline is honest about its evidence base: no recommendation reaches Grade A, nineteen are Grade B, and six fall into Grade C or D. Some recommendations rest on moderate, low, or very low quality evidence, reflecting the current state of off-label anti-tuberculosis drug research, and more high-quality clinical studies are needed. This article is an interpretation for professional education; it is not clinical advice, and it does not replace the drug label, the original guideline, or your institution's rules.

Bottom line

The 2026 guideline turns twenty five off-label anti-tuberculosis drug use situations into citeable recommendations for 13 drugs, from bedaquiline beyond 24 weeks to the delamanid albumin limit and the clavulanic acid rule for carbapenems. For frontline clinicians, its real value is not perfect evidence but a traceable source: every off-label decision now has a recommendation number, a strength grade, and a monitoring requirement to document in the chart.

FAQ

What is off-label anti-tuberculosis drug use?

Off-label anti-tuberculosis drug use means giving a tuberculosis drug in a way its label does not approve: a higher dose, a longer course, a new patient group, or a different route such as inhalation or injection. It is common in resistant and severe tuberculosis because guidelines adopt new drugs and regimens before labels are updated. The 2026 guideline gives 25 evidence-graded recommendations for 13 drugs and requires informed consent and institutional review before use.

Which law allows off-label use in China?

Article 29 of the Physician Law of China, effective since March 1, 2022, allows off-label use in special situations where no effective or better treatment exists. It has three paragraphs: the prescribing principle, the exception channel with explicit informed consent, and the hospital duty to review prescriptions. All three must be read together, and meeting them makes the use lawful.

What three conditions must be met at the same time?

All three conditions are required and none is optional. First, clinical necessity: no effective or better treatment exists and no reasonable substitute drug is available. Second, evidence-based support from guidelines, consensus documents, systematic reviews, trials, or meta-analyses, not for experimental purposes. Third, informed consent: written confirmation from the patient or legal guardian after explanation of the unapproved use and its risks. The hospital's review process must also be completed.

Can bedaquiline be used beyond 24 weeks?

Yes. The guideline lists use beyond 24 weeks as an off-label situation for bedaquiline in adult rifampicin resistant tuberculosis and in children of any age, with a weak recommendation and moderate evidence. The exact duration follows the regimen being used. During treatment, clinicians should monitor QTcF prolongation and liver function, with closer ECG checks in older adults, heart disease, electrolyte disturbance, or when combined with other QT-prolonging drugs.

When should delamanid not be started?

Delamanid must not be started when serum albumin is below 28 g per liter. This is a strong recommendation with moderate evidence and a hard threshold with no room for individualization. Serum albumin should be checked before and during treatment, together with QTcF and serum electrolytes. Patients with long-term malnutrition, liver disease, or critical illness should have albumin checked in advance.

Why is clavulanic acid given with every carbapenem dose?

Clavulanic acid inhibits the BlaC enzyme of tuberculosis bacteria. Without it, the value of carbapenems in an anti-tuberculosis regimen is greatly reduced. The guideline states that every dose of meropenem or imipenem/cilastatin must be combined with clavulanic acid; this is not an optional add-on but a condition for the regimen to work. This step is easily missed in clinical practice.

Is high dose rifampicin recommended for routine use?

No. High dose rifampicin at 15 to 35 mg per kg currently has mainly research value for dose optimization and course shortening, and routine use is not recommended. Individualized high doses may be considered for tuberculosis meningitis intensification under a specialist team, but this remains individualized, not routine.

What are the TDM reference ranges for levofloxacin and moxifloxacin?

The guideline gives empirical reference ranges only, not fixed treatment targets. For levofloxacin the Cmax reference is 8 to 12 mg per liter. For moxifloxacin it is 3 to 5 mg per liter. Results must be interpreted together with dose, sampling time, treatment response, and adverse reactions; dosing should not be forced into these ranges.

Can children receive levofloxacin for multidrug resistant tb?

Yes. Levofloxacin can be used for multidrug resistant and rifampicin resistant tuberculosis in children of any age, with a weak recommendation and moderate evidence. Doses are stratified by age and weight. For drug-sensitive tuberculosis in children, levofloxacin is used only as an individualized substitute when a standard regimen cannot be composed.

What is the 3H2P2 preventive regimen?

The 3H2P2 regimen is isoniazid 500 to 600 mg per dose plus rifapentine 450 to 600 mg per dose, twice weekly, for three months. It is for preventive treatment of tuberculosis infection. The guideline rates this as a strong recommendation with moderate evidence and calls it the highest-quality, most China-specific evidence in the document, based on Chinese population pharmacokinetics and safety data.

What replaces linezolid when bone marrow suppression occurs?

When a patient cannot tolerate linezolid, or has high toxicity risk such as baseline bone marrow suppression or nervous system disease, and the regimen still needs an oxazolidinone, contezolid may be considered after assessment. This is a new addition in 2026 with a weak recommendation and low evidence: it is a considered option, not a default switch. The reason for switching, the assessment, and informed consent must be recorded.

Is clofazimine always off label for tuberculosis?

Yes. In tuberculosis, every use of clofazimine is off-label. It is a group B drug in long multidrug resistant tuberculosis regimens and part of some six-month and nine-month regimens. Adults take 100 mg once daily with food; children take 2 to 5 mg per kg per dose once daily, up to 100 mg per day, and soft capsules should not be opened. Clinicians should monitor skin and mucosa pigmentation and QTcF, and warn patients that pigmentation may take months to fade after stopping.