Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

latent TB infection: non-pregnant

1st line – treatment for latent TB infection

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INITIAL
|
latent TB infection: non-pregnant
1st line – 

treatment for latent TB infection

People who have had significant exposure to an active infectious TB case in the previous 1 to 2 years should be evaluated for active TB disease and latent TB infection (LTBI). A repeat test for LTBI (TB skin test or interferon-gamma release assay) is recommended 8 to 10 weeks after the last exposure, if the initial evaluation was performed prior to this and the initial test result was negative.

Treatment for latent infection can be considered prior to this, and in people with a positive skin test (usually taken to be induration ≥5 mm in this patient group) but no clinical or bacteriological sign of active infection.

The decision whether to treat depends on the duration, proximity, and environment of exposure, as well as the immune status of the exposed contacts.[9]

For patients with LTBI that is presumed to be susceptible to isoniazid or rifampicin, World Health Organization (WHO) guidelines recommend the following regimens regardless of HIV status: 6 or 9 months of daily isoniazid (all ages), 3 months of weekly rifapentine plus isoniazid (age 2 years and over), or 3 months of daily isoniazid plus rifampicin (all ages).[66] One month of daily rifapentine plus isoniazid (age 13 years and over) or 4 months of daily rifampicin (all ages) are alternative regimens.[66] Rifamycins should only be used if there are no significant interactions with other medications (e.g., antiretroviral therapy). 

Peripheral neuropathy is a common adverse effect of isoniazid due to pyridoxine antagonism. Pyridoxine supplementation should therefore be considered for prevention of peripheral neuropathy in patients with latent infection taking isoniazid, particularly in those in whom neuropathy is common (e.g., diabetes, uraemia, alcoholism, malnutrition, HIV infection), pregnant women, or patients with seizure disorders.[21][66][67]

Ideally, all medications within a given regimen should be administered at the same time of day if possible. If the patient cannot tolerate the pill burden, different medications can be administered separately, but the dose of each individual medication should not be split up. Consult guidelines for dosing information.[9]

Rifapentine may not be available in some countries.

Patients with complex comorbidity, or for whom treatment is contraindicated, should be managed after expert consultation.

For patients with LTBI presumed to be due to contact with an infectious patient with drug-resistant TB, expert consultation should be sought.[66][67][68][69] For patients exposed to isoniazid-resistant TB, 4 months of daily rifampicin may be an option.[66][68]​ ​US guidelines recommend that patients with multidrug-resistant (MDR) TB are treated with 6 to 12 months of a fluoroquinolone (i.e., levofloxacin or moxifloxacin) alone or in combination with a second agent based on susceptibility testing of the source isolate.[69] Specific regimens are not detailed here. WHO guidelines recommend that in selected high-risk household contacts of patients with MDR TB, preventive treatment may be considered based on individualised risk assessment, and a sound clinical justification.[66]

Primary options

isoniazid: children <10 years of age: 7-15 mg/kg orally once daily for 6 or 9 months, maximum 300 mg/dose; children ≥10 years of age and adults: 5 mg/kg orally once daily for 6 or 9 months, maximum 300 mg/dose

More

OR

isoniazid: children 2-14 years of age and body weight 10-15 kg: 300 mg orally once weekly for 3 months; children 2-14 years of age and body weight 16-23 kg: 500 mg orally once weekly for 3 months; children 2-14 years of age and body weight 24-30 kg: 600 mg orally once weekly for 3 months; children 2-14 years of age and body weight >30 kg: 700 mg orally once weekly for 3 months; children >14 years of age and adults: 900 mg orally once weekly for 3 months

More

and

rifapentine: children 2-14 years of age and body weight 10-15 kg: 300 mg orally once weekly for 3 months; children 2-14 years of age and body weight 16-23 kg: 450 mg orally once weekly for 3 months; children 2-14 years of age and body weight 24-30 kg: 600 mg orally once weekly for 3 months; children 2-14 years of age and body weight >30 kg: 750 mg orally once weekly for 3 months; children >14 years of age and adults: 900 mg orally once weekly for 3 months

OR

isoniazid: children <10 years of age: 7-15 mg/kg orally once daily for 3 months, maximum 300 mg/dose; children ≥10 years of age and adults: 5 mg/kg orally once daily for 3 months, maximum 300 mg/dose

More

and

rifampicin: children <10 years of age: 10-20 mg/kg orally once daily for 3 months, maximum 600 mg/dose; children ≥10 years of age and adults: 10 mg/kg orally once daily for 3 months, maximum 600 mg/dose

Secondary options

isoniazid: children ≥13 years of age and adults: 300 mg orally once daily for 1 month

More

and

rifapentine: children ≥13 years of age and adults: 600 mg orally once daily for 1 month

OR

rifampicin: children <10 years of age: 10-20 mg/kg orally once daily for 4 months, maximum 600 mg/dose; children ≥10 years of age and adults: 10 mg/kg orally once daily for 4 months, maximum 600 mg/dose

latent TB infection: pregnant

1st line – specialty consultation

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INITIAL
|
latent TB infection: pregnant
1st line – 

specialty consultation

Pregnancy has minimal influence on progression of latent TB infection to active disease, and pregnant women should be tested based on the presence of risk factors. If there is a high risk for progression to TB (e.g., recent TB infection, HIV infected), immediate treatment is indicated. Otherwise treatment may be deferred until at least 3 months postnatal because of increased incidence of serious drug-induced hepatitis during perinatal period.

Specialist consultation is recommended in pregnancy.

ACUTE

active TB HIV-negative non-pregnant: no hepatic dysfunction

1st line – intensive phase therapy

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ACUTE
|
active TB HIV-negative non-pregnant: no hepatic dysfunction
|
drug resistance not suspected
1st line – 

intensive phase therapy

WHO guidelines for the treatment of drug-susceptible active pulmonary TB include regimens that are given for a total duration of 4 or 6 months.[70]

The standard 6-month regimen is recommended by the WHO for new patients with pulmonary TB. The initial intensive phase treatment for the 6-month regimen includes the preferred drugs of isoniazid, rifampicin, pyrazinamide, and ethambutol, and lasts 2 months.[70] Patients aged between 3 months and 16 years with non-severe TB (defined as uncomplicated TB pleural effusion or paucibacillary, non-cavitary disease, confined to one lobe of the lungs, and without a miliary pattern) may receive a 4-month version of this regimen. The intensive phase of this regimen includes daily administration of isoniazid, rifampicin, and pyrazinamide, with or without ethambutol, for 2 months.[30]​​​​[70] Ethambutol should be included in areas of high prevalence of HIV or isoniazid resistance.[30]​​​​[70] Children and adolescents who do not meet the criteria for non-severe TB should receive the standard 6-month treatment regimen (including ethambutol).[30]​​​​[70]

Patients aged 12 years and over may receive a 4-month regimen of isoniazid, rifapentine, moxifloxacin, and pyrazinamide. The intensive phase of this regimen includes daily administration of isoniazid, rifapentine, moxifloxacin, and pyrazinamide and also lasts 2 months.[70][71]​​ This regimen is not currently recommended for young children, persons who are pregnant, and patients with HIV infection and CD4 count of <100 cells/microlitre.[70]

Pyridoxine should be administered with isoniazid to help prevent isoniazid-associated neuropathy, and is recommended in all cases of active TB.

Pyrazinamide is used during the initial phase only. It is not recommended for patients with acute gouty arthritis (but can be used in patients with past history of gout) because of little information about the safety data.

Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycaemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behaviour.[85] Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.​

Expert consultation should be sought in patients with a creatinine clearance of <30 mL/minute.

Primary options

4- or 6-month regimen

isoniazid: 7-15 mg/kg orally once daily, maximum 300 mg/dose; adults: 5 mg/kg orally once daily, maximum 300 mg/dose

More

and

rifampicin: children: 10-20 mg/kg orally once daily, maximum 600 mg/dose; adults: 10 mg/kg orally once daily, maximum 600 mg/dose

and

pyrazinamide: children: 30-40 mg/kg orally once daily; adults: consult specialist for guidance on dose (dose is based on lean body weight and available tablet formulation)

and

ethambutol: children: 15-25 mg/kg orally once daily; adults: consult specialist for guidance on dose (dose is based on lean body weight and available tablet formulation)

More

OR

4-month regimen

isoniazid: children ≥12 years of age and ≥40 kg body weight and adults: 300 mg orally once daily

More

and

rifapentine: children ≥12 years of age and ≥40 kg body weight and adults: 1200 mg orally once daily

and

moxifloxacin: children ≥12 years of age and ≥40 kg body weight and adults: 400 mg orally once daily

and

pyrazinamide: children ≥12 years of age and ≥40 kg body weight and adults: consult specialist for guidance on dose (dose is based on lean body weight and available tablet formulation)

Plus – continuation phase therapy

Back
ACUTE
|
active TB HIV-negative non-pregnant: no hepatic dysfunction
|
drug resistance not suspected
Plus – 

continuation phase therapy

Treatment recommended for ALL patients in selected patient group

WHO guidelines recommend that patients completing the initial intensive standard regimen of isoniazid, rifampicin, pyrazinamide, and ethambutol continue to receive isoniazid and rifampicin in the continuation phase for 4 months (a total of 6 months treatment). Children aged 3 months to 16 years with non-severe pulmonary TB should receive 2 months of continuation phase therapy (4 months total). Those with severe TB, and also children aged less than 3 months, should receive the standard 6-month treatment regimen.[30]​​​​[70]

In the continuation phase of the 4-month isoniazid, rifapentine, moxifloxacin, and pyrazinamide regimen, isoniazid, rifapentine, and moxifloxacin are given for another 2 months (total of 4 months).[70][71]​ 

Ideally, all medications within a given regimen should be administered at the same time of day if possible. If the patient cannot tolerate the pill burden, different medications can be administered separately, but the dose of each individual medication should not be split up. Daily therapy is preferred throughout the continuation phase.

Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycaemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behaviour.[85] Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.

Pyridoxine should be administered with isoniazid to help prevent isoniazid-associated neuropathy, and is recommended in all cases of active TB.

Primary options

4- or 6-month regimen

isoniazid: children: 7-15 mg/kg orally once daily, maximum 300 mg/dose; adults: 5 mg/kg orally once daily, maximum 300 mg/dose

More

and

rifampicin: children: 10-20 mg/kg orally once daily, maximum 600 mg/dose; adults: 10 mg/kg orally once daily, maximum 600 mg/dose

OR

4-month regimen

isoniazid: children ≥12 years of age and ≥40 kg body weight and adults: 300 mg orally once daily

More

and

rifapentine: children ≥12 years of age and ≥40 kg body weight and adults: 1200 mg orally once daily

and

moxifloxacin: children ≥12 years of age and ≥40 kg body weight and adults: 400 mg orally once daily

1st line – antituberculosis treatment

Back
ACUTE
|
active TB HIV-negative non-pregnant: no hepatic dysfunction
|
isoniazid resistance
1st line – 

antituberculosis treatment

Isoniazid-resistant TB is defined as resistance to isoniazid and susceptibility to rifampicin that has been confirmed in vitro.

In patients with confirmed rifampicin-susceptible and isoniazid-resistant TB, the WHO recommends treatment with rifampicin, ethambutol, pyrazinamide, and levofloxacin for a duration of 6 months.[81] If levofloxacin cannot be used (because of toxicity or resistance) WHO recommends that the patient is treated with rifampicin, ethambutol, and pyrazinamide for 6 months.[81]

Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycaemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behaviour.[85] Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.​

Resistance to rifampicin must be excluded before starting the regimen, and preferably, resistance to fluoroquinolones and pyrazinamide would also be excluded. If isoniazid resistance is identified after a patient has started a regimen for drug-susceptible TB, rapid molecular testing for rifampicin resistance should be done, and if rifampicin resistance is excluded, the patient should begin a full 6-month course of rifampicin, ethambutol, pyrazinamide, and levofloxacin. If rifampicin resistance is detected, the patient should begin an appropriate treatment regimen for MDR TB.[81]

In contrast to regimens for drug-susceptible and MDR TB, the WHO recommended treatment regimen for isoniazid-resistant TB does not have initial intensive and continuation phases.

Primary options

rifampicin

and

ethambutol

and

pyrazinamide

and

levofloxacin

Secondary options

rifampicin

and

ethambutol

and

pyrazinamide

1st line – standardised 6-month regimen

Back
ACUTE
|
active TB HIV-negative non-pregnant: no hepatic dysfunction
|
multidrug resistance
1st line – 

standardised 6-month regimen

The 6-month all-oral regimen recommended by the WHO is composed of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM).[81][83][84]​​​​​ The WHO advises that if the patient has documented resistance to fluoroquinolones, then the regimen should continue without moxifloxacin (BPaL); although initiation of BPaLM should not be delayed while waiting for results of drug susceptibility testing.

The WHO recommends the use of this 6-month regimen over the 9-month or longer MDR/rifampicin-resistant-TB regimens for adults and adolescents aged 14 and over, regardless of HIV status, who have less than 1 month exposure to bedaquiline, linezolid, pretomanid, or delamanid.[81]

Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycaemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behaviour.[85] Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.​

Specific regimens should be selected by a specialist in the treatment of MDR TB. Consult specialist for guidance on doses.

Primary options

bedaquiline

and

pretomanid

and

linezolid

and

moxifloxacin

Consider – surgery

Back
ACUTE
|
active TB HIV-negative non-pregnant: no hepatic dysfunction
|
multidrug resistance
Consider – 

surgery

Additional treatment recommended for SOME patients in selected patient group

In patients with rifampicin-resistant TB or MDR TB, elective partial lung resection (i.e., lobectomy or wedge resection) may be used alongside a recommended MDR TB regimen.[81]

1st line – standardised 9-month regimen (intensive phase)

Back
ACUTE
|
active TB HIV-negative non-pregnant: no hepatic dysfunction
|
multidrug resistance
1st line – 

standardised 9-month regimen (intensive phase)

The 9-month all-oral regimen is recommended by the WHO over the longer MDR/rifampicin-resistant-TB regimens (18 months or more) when resistance to fluoroquinolones has been excluded and can be used when patients are not eligible for the 6-month regimen.

In the intensive phase of the 9-month regimen, bedaquiline is used for 6 months in combination with levofloxacin/moxifloxacin, ethionamide, ethambutol, isoniazid (high-dose), pyrazinamide, and clofazimine for 4 months (with the possibility of extending to 6 months if the patient remains sputum smear positive at the end of 4 months).​ Two months of linezolid may be used in place of the 4 months of ethionamide.[81]​

The WHO recommends the use of the 9-month regimen for adults and children without extensive TB disease, regardless of HIV status, and who have less than 1 month exposure to bedaquiline, fluoroquinolones, ethionamide, linezolid, and clofazimine.[81]

Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycaemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behaviour.[85] Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.​

Specific regimens should be selected by a specialist in the treatment of MDR TB. Consult specialist for guidance on doses.

Primary options

bedaquiline

-- AND --

levofloxacin

or

moxifloxacin

-- AND --

ethionamide

or

linezolid

-- AND --

clofazimine

-- AND --

isoniazid

-- AND --

pyrazinamide

-- AND --

ethambutol

Plus – standardised 9-month term regimen (continuation phase)

Back
ACUTE
|
active TB HIV-negative non-pregnant: no hepatic dysfunction
|
multidrug resistance
Plus – 

standardised 9-month term regimen (continuation phase)

Treatment recommended for ALL patients in selected patient group

The continuation phase of the 9-month regimen consists of 5 months of treatment with levofloxacin/moxifloxacin, clofazimine, ethambutol, and pyrazinamide.[81]

Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycaemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behaviour.[85] Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.​

Management of patients with additional comorbidities is complex and will require specialist advice.

Specific regimens should be selected by a specialist in the treatment of MDR TB. Consult specialist for guidance on doses.

Primary options

levofloxacin

or

moxifloxacin

-- AND --

clofazimine

-- AND --

pyrazinamide

-- AND --

ethambutol

Consider – surgery

Back
ACUTE
|
active TB HIV-negative non-pregnant: no hepatic dysfunction
|
multidrug resistance
Consider – 

surgery

Additional treatment recommended for SOME patients in selected patient group

In patients with rifampicin-resistant TB or MDR TB, elective partial lung resection (i.e., lobectomy or wedge resection) may be used alongside a recommended MDR TB regimen.[81]

1st line – standardised or individualised longer term regimen

Back
ACUTE
|
active TB HIV-negative non-pregnant: no hepatic dysfunction
|
multidrug resistance
1st line – 

standardised or individualised longer term regimen

The longer term regimen is recommended for all patients who do not fulfil the criteria for the shorter term regimens.[81]

The longer term regimen, previously referred to as conventional treatment, refers to regimens for rifampicin-resistant (RR) TB or MDR TB, which last 18 months or more and which may be standardised or individualised. The WHO guidelines recommend that patients with RR-TB or MDR TB on longer regimens receive treatment with at least four TB agents likely to be effective, including all three group A agents and at least one Group B agent, and that at least three agents are included for the rest of treatment if bedaquiline is stopped. If only one or two Group A agents are used, both Group B agents should be included. If the regimen cannot be composed with agents from Groups A and B alone, Group C agents are added to complete it.​[81]

A treatment duration of 15-17 months after culture conversion is suggested for most patients; however, the duration may be modified according to the patient’s response to therapy. In longer regimens containing amikacin or streptomycin, an intensive phase of 6-7 months is suggested for most patients, but again, the duration may be modified according to the patient’s response to therapy.

Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycaemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behaviour.[85] Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.​

Management of drug-resistant TB requires expert consultation.

Primary options

Group A (include all 3 drugs)

levofloxacin

or

moxifloxacin

-- AND --

bedaquiline

-- AND --

linezolid

OR

Group B (add 1 or both drugs)

clofazimine

-- AND / OR --

cycloserine

or

terizidone

OR

Group C (add to complete the regimen and when drugs from groups A and B cannot be used)

ethambutol

OR

delamanid

OR

pyrazinamide

OR

imipenem/cilastatin

or

meropenem

OR

amikacin

or

streptomycin

OR

ethionamide

or

prothionamide

OR

aminosalicylic acid

Consider – surgery

Back
ACUTE
|
active TB HIV-negative non-pregnant: no hepatic dysfunction
|
multidrug resistance
Consider – 

surgery

Additional treatment recommended for SOME patients in selected patient group

In patients with rifampicin-resistant TB or MDR TB, elective partial lung resection (i.e., lobectomy or wedge resection) may be used alongside a recommended MDR TB regimen.[81]

active TB HIV-positive non-pregnant: no hepatic dysfunction

1st line – intensive phase therapy

Back
ACUTE
|
active TB HIV-positive non-pregnant: no hepatic dysfunction
|
drug resistance not suspected
1st line – 

intensive phase therapy

Treatment of HIV-positive patients is similar to that of non-HIV-positive patients.[70]

WHO guidelines for the treatment of drug-susceptible active pulmonary TB include regimens that are given for a total duration of 4 or 6 months.[70]

The standard 6-month regimen is recommended by the WHO for new patients with pulmonary TB. The initial intensive phase treatment for the 6-month regimen includes the preferred drugs of isoniazid, rifampicin, pyrazinamide, and ethambutol, and lasts 2 months.[70] Patients aged between 3 months and 16 years with non-severe TB (defined as uncomplicated TB pleural effusion or paucibacillary, non-cavitary disease, confined to one lobe of the lungs, and without a miliary pattern) may receive a 4-month version of this regimen. The intensive phase of this regimen includes daily administration of isoniazid, rifampicin, and pyrazinamide, with or without ethambutol, for 2 months.[30]​​​​[70] Ethambutol should be included in areas of high prevalence of HIV or isoniazid resistance.[30]​​​​[70] Children and adolescents who do not meet the criteria for non-severe TB should receive the standard 6-month treatment regimen (including ethambutol).[30]​​​​[70]

Patients aged 12 years and over may receive a 4-month regimen of isoniazid, rifapentine, moxifloxacin, and pyrazinamide. The intensive phase of this regimen includes daily administration of isoniazid, rifapentine, moxifloxacin, and pyrazinamide and also lasts 2 months.[70][71]​ This regimen is not currently recommended for young children, persons who are pregnant, and patients with HIV infection and CD4 count of <100 cells/microlitre.[70]

Pyridoxine should be administered with isoniazid to help prevent isoniazid-associated neuropathy, and is recommended in all cases of active TB.

Pyrazinamide is used during the initial phase only. It is not recommended for patients with acute gouty arthritis (but can be used in patients with past history of gout) because of little information about the safety data.

Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycaemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behaviour.[85] Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.​

Expert consultation should be sought in patients with a creatinine clearance of <30 mL/minute.

If the patient is on ART, there are some additional considerations including the potential for drug interactions, especially between rifampicin and non-nucleoside reverse-transcriptase inhibitors or protease-inhibitors. For this reason, rifabutin may be considered as an alternative to rifampicin. Specialist consultation is recommended when considering use of rifabutin.

Primary options

4- or 6-month regimen

isoniazid: children: 7-15 mg/kg orally once daily, maximum 300 mg/dose; adults: 5 mg/kg orally once daily, maximum 300 mg/dose

More

and

rifampicin: children: 10-20 mg/kg orally once daily, maximum 600 mg/dose; adults: 10 mg/kg orally once daily, maximum 600 mg/dose

and

pyrazinamide: children: 30-40 mg/kg orally once daily; adults: consult specialist for guidance on dose (dose is based on lean body weight and available tablet formulation)

and

ethambutol: children: 15-25 mg/kg orally once daily; adults: consult specialist for guidance on dose (dose is based on lean body weight and available tablet formulation)

More

OR

4-month regimen

isoniazid: children ≥12 years of age and ≥40 kg body weight and adults: 300 mg orally once daily

More

and

rifapentine: children ≥12 years of age and ≥40 kg body weight and adults: 1200 mg orally once daily

and

moxifloxacin: children ≥12 years of age and ≥40 kg body weight and adults: 400 mg orally once daily

and

pyrazinamide: children ≥12 years of age and ≥40 kg body weight and adults: consult specialist for guidance on dose (dose is based on lean body weight and available tablet formulation)

Secondary options

4- or 6-month regimen

isoniazid: children: 7-15 mg/kg orally once daily, maximum 300 mg/dose; adults: 5 mg/kg orally once daily, maximum 300 mg/dose

More

and

rifabutin: children and adults: consult specialist for guidance on dose

More

and

pyrazinamide: children: 30-40 mg/kg orally once daily; adults: consult specialist for guidance on dose (dose is based on lean body weight and available tablet formulation)

and

ethambutol: children: 15-25 mg/kg orally once daily; adults: consult specialist for guidance on dose (dose is based on lean body weight and available tablet formulation)

More

Plus – continuation phase therapy

Back
ACUTE
|
active TB HIV-positive non-pregnant: no hepatic dysfunction
|
drug resistance not suspected
Plus – 

continuation phase therapy

Treatment recommended for ALL patients in selected patient group

Treatment of HIV-positive patients is similar to that of non-HIV-positive patients.[70]

The WHO guidelines recommend that patients completing the initial intensive standard regimen of isoniazid, rifampicin, pyrazinamide, and ethambutol continue to receive isoniazid and rifampicin in the continuation phase for 4 months (a total of 6 months treatment). Children aged 3 months to 16 years with non-severe pulmonary TB should receive 2 months of continuation phase therapy (4 months total). Those with severe TB, and also children aged less than 3 months, should receive the standard 6-month treatment regimen.[30]​​​​[70]

In the continuation phase of the 4-month isoniazid, rifapentine, moxifloxacin, and pyrazinamide regimen, isoniazid, rifapentine, and moxifloxacin are given for another 2 months (total of 4 months).[70][71]​ This regimen is not currently recommended for young children, persons who are pregnant, and patients with HIV infection and CD4 count of <100 cells/microlitre.[70]

Ideally, all medications within a given regimen should be administered at the same time of day if possible. If the patient cannot tolerate the pill burden, different medications can be administered separately, but the dose of each individual medication should not be split up. Daily therapy is preferred throughout the continuation phase.

Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycaemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behaviour.[85] Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.​

Pyridoxine should be administered with isoniazid to help prevent isoniazid-associated neuropathy, and is recommended in all cases of active TB.

If the patient is on ART, there are some additional considerations including the potential for drug interactions, especially between rifampicin and non-nucleoside reverse-transcriptase inhibitors or protease-inhibitors. For this reason, rifabutin may be considered as an alternative to rifampicin. Specialist consultation is recommended when considering use of rifabutin.

Primary options

4- or 6-month regimen

isoniazid: children: 7-15 mg/kg orally once daily, maximum 300 mg/dose; adults: 5 mg/kg orally once daily, maximum 300 mg/dose

More

and

rifampicin: children: 10-20 mg/kg orally once daily, maximum 600 mg/dose; adults: 10 mg/kg orally once daily, maximum 600 mg/dose

OR

4-month regimen

isoniazid: children ≥12 years of age and ≥40 kg body weight and adults: 300 mg orally once daily

More

and

rifapentine: children ≥12 years of age and ≥40 kg body weight and adults: 1200 mg orally once daily

and

moxifloxacin: children ≥12 years of age and ≥40 kg body weight and adults: 400 mg orally once daily

Secondary options

4- or 6-month regimen

isoniazid: children: 7-15 mg/kg orally once daily, maximum 300 mg/dose; adults: 5 mg/kg orally once daily, maximum 300 mg/dose

More

and

rifabutin: children and adults: consult specialist for guidance on dose

More

1st line – antituberculosis treatment

Back
ACUTE
|
active TB HIV-positive non-pregnant: no hepatic dysfunction
|
isoniazid resistance
1st line – 

antituberculosis treatment

Isoniazid-resistant TB is defined as resistance to isoniazid and susceptibility to rifampicin that has been confirmed in vitro.

In patients with confirmed rifampicin-susceptible and isoniazid-resistant TB, the WHO recommends treatment with rifampicin, ethambutol, pyrazinamide and levofloxacin or a duration of 6 months.[81] If levofloxacin cannot be used (because of toxicity or resistance) WHO recommends that the patient is treated with rifampicin, ethambutol, and pyrazinamide for 6 months.[81]

Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycaemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behaviour.[85] Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.​

Resistance to rifampicin must be excluded before starting the regimen, and preferably, resistance to fluoroquinolones and pyrazinamide would also be excluded. If isoniazid resistance is identified after a patient has started a regimen for drug-susceptible TB, rapid molecular testing for rifampicin resistance should be done, and if rifampicin resistance is excluded, the patient should begin a full 6-month course of rifampicin, ethambutol, pyrazinamide, and levofloxacin. If rifampicin resistance is detected the patient should begin an appropriate treatment regimen for MDR TB.[81]

In contrast to regimens for drug-susceptible and MDR TB, the WHO recommended treatment regimens for isoniazid-resistant TB does not have initial intensive and continuation phases.

Primary options

rifampicin

and

ethambutol

and

pyrazinamide

and

levofloxacin

Secondary options

rifampicin

and

ethambutol

and

pyrazinamide

1st line – standardised 6-month regimen

Back
ACUTE
|
active TB HIV-positive non-pregnant: no hepatic dysfunction
|
multidrug resistance
1st line – 

standardised 6-month regimen

The 6-month all-oral regimen recommended by the WHO is composed of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM).[81][83][84]​​​​​​ The WHO advises that if the patient has documented resistance to fluoroquinolones, then the regimen should continue without moxifloxacin (BPaL); although initiation of BPaLM should not be delayed while waiting for results of drug susceptibility testing.

The WHO recommends the use of this 6-month regimen over the 9-month or longer MDR/rifampicin-resistant-TB regimens for adults and adolescents aged 14 and over, regardless of HIV status, who have less than 1 month exposure to bedaquiline, linezolid, pretomanid, or delamanid.[81]​

Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycaemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behaviour.[85] Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.​

Specific regimens should be selected by a specialist in the treatment of MDR TB. Consult specialist for guidance on doses.

Primary options

bedaquiline

and

pretomanid

and

linezolid

and

moxifloxacin

Consider – surgery

Back
ACUTE
|
active TB HIV-positive non-pregnant: no hepatic dysfunction
|
multidrug resistance
Consider – 

surgery

Additional treatment recommended for SOME patients in selected patient group

In patients with rifampicin-resistant TB or MDR TB, elective partial lung resection (i.e., lobectomy or wedge resection) may be used alongside a recommended MDR TB regimen.[81]

1st line – standardised 9-month regimen (intensive phase)

Back
ACUTE
|
active TB HIV-positive non-pregnant: no hepatic dysfunction
|
multidrug resistance
1st line – 

standardised 9-month regimen (intensive phase)

The 9-month all-oral regimen is recommended by the WHO over the longer MDR/rifampicin-resistant-TB regimens (18 months or more) when resistance to fluoroquinolones has been excluded and can be used when patients are not eligible for the 6-month regimen.

In the intensive phase of the 9-month regimen, bedaquiline is used for 6 months in combination with levofloxacin/moxifloxacin, ethionamide, ethambutol, isoniazid (high-dose), pyrazinamide, and clofazimine for 4 months (with the possibility of extending to 6 months if the patient remains sputum smear positive at the end of 4 months).​ Two months of linezolid may be used in place of the 4 months of ethionamide.[81]​

The WHO recommends the use of the 9-month regimen for adults and children without extensive TB disease, regardless of HIV status, and who have less than 1 month exposure to bedaquiline, fluoroquinolones, ethionamide, linezolid, and clofazimine.[81]

Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycaemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behaviour.[85] Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.​

Specific regimens should be selected by a specialist in the treatment of MDR TB. Consult specialist for guidance on doses.

Primary options

bedaquiline

-- AND --

levofloxacin

or

moxifloxacin

-- AND --

ethionamide

or

linezolid

-- AND --

clofazimine

-- AND --

isoniazid

-- AND --

pyrazinamide

-- AND --

ethambutol

Plus – standardised 9-month term regimen (continuation phase)

Back
ACUTE
|
active TB HIV-positive non-pregnant: no hepatic dysfunction
|
multidrug resistance
Plus – 

standardised 9-month term regimen (continuation phase)

Treatment recommended for ALL patients in selected patient group

The continuation phase of the 9-month regimen consists of 5 months of treatment with levofloxacin/moxifloxacin, clofazimine, ethambutol, and pyrazinamide.[81]

Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycaemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behaviour.[85] Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.​

Management of patients with additional comorbidities is complex and will require specialist advice.

Specific regimens should be selected by a specialist in the treatment of MDR TB. Consult specialist for guidance on doses.

Primary options

levofloxacin

or

moxifloxacin

-- AND --

clofazimine

-- AND --

pyrazinamide

-- AND --

ethambutol

Consider – surgery

Back
ACUTE
|
active TB HIV-positive non-pregnant: no hepatic dysfunction
|
multidrug resistance
Consider – 

surgery

Additional treatment recommended for SOME patients in selected patient group

In patients with rifampicin-resistant TB or MDR TB, elective partial lung resection (i.e., lobectomy or wedge resection) may be used alongside a recommended MDR TB regimen.[81]

1st line – standardised or individualised longer term regimen

Back
ACUTE
|
active TB HIV-positive non-pregnant: no hepatic dysfunction
|
multidrug resistance
1st line – 

standardised or individualised longer term regimen

The longer term regimen is recommended for all patients who do not fulfil the criteria for the shorter term regimens.[81]

The longer term regimen, previously referred to as conventional treatment, refers to regimens for rifampicin-resistant (RR) TB or MDR TB, which last 18 months or more and which may be standardised or individualised. The 2020 World Health Organization guidelines recommend that patients with RR-TB or MDR-TB on longer regimens receive treatment with at least four TB agents likely to be effective, including all three group A agents and at least one Group B agent, and that at least three agents are included for the rest of treatment if bedaquiline is stopped. If only one or two Group A agents are used, both Group B agents should be included. If the regimen cannot be composed with agents from Groups A and B alone, Group C agents are added to complete it.​[81]

A treatment duration of 15-17 months after culture conversion is suggested for most patients; however, the duration may be modified according to the patient’s response to therapy. In longer regimens containing amikacin or streptomycin, an intensive phase of 6-7 months is suggested for most patients, but again, the duration may be modified according to the patient’s response to therapy.

Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycaemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behaviour.[85] Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.​

Management of drug-resistant TB requires expert consultation.

Primary options

Group A (include all 3 drugs)

levofloxacin

or

moxifloxacin

-- AND --

bedaquiline

-- AND --

linezolid

OR

Group B (add 1 or both drugs)

clofazimine

-- AND / OR --

cycloserine

or

terizidone

OR

Group C (add to complete the regimen and when drugs from groups A and B cannot be used)

ethambutol

OR

delamanid

OR

pyrazinamide

OR

imipenem/cilastatin

or

meropenem

OR

amikacin

or

streptomycin

OR

ethionamide

or

prothionamide

OR

aminosalicylic acid

Consider – surgery

Back
ACUTE
|
active TB HIV-positive non-pregnant: no hepatic dysfunction
|
multidrug resistance
Consider – 

surgery

Additional treatment recommended for SOME patients in selected patient group

In patients with rifampicin-resistant TB or MDR TB, elective partial lung resection (lobectomy or wedge resection) may be used alongside a recommended MDR TB regimen.[81]

active TB pregnant

1st line – speciality consultation

Back
ACUTE
|
active TB pregnant
1st line – 

speciality consultation

Specialist consultation is recommended in the treatment of TB in pregnancy.

active TB non-pregnant: pre-existing or drug-induced hepatic dysfunction

1st line – speciality consultation

Back
ACUTE
|
active TB non-pregnant: pre-existing or drug-induced hepatic dysfunction
1st line – 

speciality consultation

Specialist consultation is recommended in the setting of drug-induced hepatic dysfunction for less hepatotoxic treatment options.

ONGOING

recurrent TB

1st line – speciality consultation

Back
ONGOING
|
recurrent TB
1st line – 

speciality consultation

Treatment failure is defined as a positive sputum smear or culture at 5 months or later during treatment.[60] When either the sputum smear or culture remains positive beyond 2-3 months into treatment, adherence with medications must be verified; emerging drug-resistant TB strains and gastrointestinal malabsorption of TB medications should also be evaluated.

Recurrence occurs in a case considered to have completed successful treatment. Recurrent cases include relapses due to the same Mycobacterium tuberculosis strain as that responsible for the previous episode, as well as new episodes of TB due to re-exposure resulting in reinfection. In non-endemic countries, recurrence is generally a result of relapse with the original organism, whereas in TB-endemic countries, it may be the result of exogenous reinfection. Relapse usually occurs in the first 6-12 months following completion of treatment and occurs in 2% to 5% of appropriately treated patients.[86]

If the patient initially had drug-susceptible isolates and treatment was directly observed, recurrence will likely result from the same susceptible organisms and prior therapy can be used. If the patient initially received self-administered therapy, there is a greater possibility of the development of a drug-resistant organism. In this situation, or if drug susceptibility has not previously been tested, an expanded MDR regimen with addition of at least two drugs not previously used should be considered.[9]

If exogenous reinfection is suspected, treatment should be based on the drug susceptibility profile of the index case, if known.

Consult specialist for guidance on appropriate combinations of agents and doses.

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