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

Back
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 1-2 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 8-10 weeks after the last exposure, if the initial evaluation was performed prior to this and the initial test result was negative.

The decision whether to treat depends on the duration, proximity, and environment of exposure, as well as the immune status of the exposed contacts.[41]

For patients with LTBI that is presumed to be susceptible to isoniazid or rifampicin, 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).[38][90] One month of daily rifapentine plus isoniazid (age 13 years and over) or 4 months of daily rifampicin (all ages) are alternative regimens.[38][90] Rifamycins should only be used if there are no significant interactions with other medications (e.g., antiretroviral therapy). World Health Organization (WHO) guidelines recommend that 3 months of daily isoniazid plus rifampicin is the preferred option for children without HIV and 6 months of daily isoniazid is the preferred regimen for children living with HIV.[38]

Peripheral neuropathy is a common adverse effect of isoniazid due to pyridoxine antagonism. Pyridoxine supplementation should therefore be considered for the 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.[33][90][92]

Ideally, all medications within a given regimen should be administered at the same time. 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.[48]

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.[91][90][92][93]​​ For patients exposed to isoniazid-resistant TB, 4 months of daily rifampicin may be an option.[90][93]​ US guidelines recommend that patients with multidrug-resistant (MDR) TB are treated with 6-12 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.[91] 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.[90]

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 – referral to specialist

Back
INITIAL
|
latent TB infection: pregnant
1st line – 

referral to specialist

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 peripartum period.

Specialist consultation is recommended in pregnancy.

ACUTE

active TB: non-pregnant, HIV-negative

1st line – intensive phase therapy

Back
ACUTE
|
active TB: non-pregnant, HIV-negative
|
drug resistance not suspected
1st line – 

intensive phase therapy

Antituberculous therapy is initiated based on clinical suspicion after optimal diagnostic samplings.

While awaiting that information, an empiric regimen may be used. The final regimen will be based on the results of drug-susceptibility testing.

All medications should be administered together.

Initial intensive-phase treatment involves the first-line drugs of isoniazid, rifampicin, pyrazinamide, and ethambutol, for 2 months with drug-susceptibility testing for those agents.[48][94]​ After 2 months, the continuation phase is started.

WHO guidelines recommend that children aged between 3 months and 16 years with non-severe TB (defined as peripheral lymph node TB; intrathoracic lymph node TB without airway obstruction; 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.[38][94]​ Ethambutol should be included in areas of high prevalence of HIV or isoniazid resistance.[38][94]​ Children and adolescents who do not meet the criteria for non-severe TB should receive the standard 6-month treatment regimen (including ethambutol) or extended treatment regimens for severe forms of extrapulmonary TB.[38][94]

An alternative option for children and adolescents with bacteriologically confirmed or clinically diagnosed TB meningitis is an intensive treatment regimen composed of 6 months of isoniazid, rifampicin, pyrazinamide, and ethionamide. The World Health Organization (WHO) recommends that this shorter intensive regimen is suitable for children and adolescents who have a low likelihood of drug resistant TB. Due to a lack of data, this regimen should not be used in children and adolescents living with HIV.[38]

Pyrazinamide is not recommended for patients experiencing acute gout as it further elevates uric acid levels. Older patients (age >75 years) may not tolerate pyrazinamide and providers may consider leaving it out of treatment regimens.[48]​ Patients who do not receive pyrazinamide during the intensive phase should receive 7 months of continuation phase (to give 9 months of total treatment).

Regimens may need to be modified in patients with hepatic injury or renal insufficiency; a specialist should be consulted for guidance on choice of regimen and appropriate doses. Several TB medications are metabolised by the liver and may potentially cause or exacerbate hepatic injury. Mild hepatitis may require only closer monitoring without changes in the standard regimen. However, severe hepatitis while on TB treatment may make it necessary to hold medications and use an alternate liver-sparing regimen. Dose adjustments may be required in patients with renal insufficiency or end-stage renal disease.[48]

As there is increased risk of retrobulbar neuritis resulting from ethambutol toxicity in patients with renal failure, particular attention to testing of visual acuity/colour discrimination and counselling of patients is also required in this population.

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/dosePyridoxine (vitamin B6) is given with isoniazid to all people at risk of neuropathy.

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)The 4-month regimen may be given with or without ethambutol.

OR

6-month TB meningitis regimen

isoniazid: children and adolescents: 20 mg/kg orally once daily, maximum 400 mg/dose

More

and

rifampicin: children and adolescents: 20 mg/kg orally once daily, maximum 600 mg/dose

and

pyrazinamide: children and adolescents: 40 mg/kg orally once daily, maximum 2000 mg/dose

and

ethionamide: children and adolescents: 20 mg/kg orally once daily, maximum 750 mg/dose

Plus – continuation phase therapy

Back
ACUTE
|
active TB: non-pregnant, HIV-negative
|
drug resistance not suspected
Plus – 

continuation phase therapy

Treatment recommended for ALL patients in selected patient group

After 2 months of intensive phase treatment in patients with drug-susceptible EPTB, pyrazinamide and ethambutol are discontinued, and isoniazid and rifampicin are given for the continuation phase. Duration of the continuation phase depends on the site of infection and severity of disease. Generally, for EPTB that does not involve CNS or bones and joints, continuation phase therapy is given for 4 months (i.e., 6 months of total treatment).

Total therapy for 9 months is considered for patients with extensive skeletal TB, especially when large joints are involved with slow clinical response. Patients with central nervous system (CNS) TB receive 7-10 months of continuation phase therapy (9-12 months total).[48][94]

Children aged 3 months to 16 years with non-severe TB should receive 2 months of continuation phase therapy (4 months total). Those with severe TB, other than TB meningitis or osteoarticular TB, and also children aged less than 3 months, should receive the standard 6-month treatment regimen.[38][94]

Children with osteoarticular TB or TB meningitis should receive 10 months of continuation phase therapy (12 months total).[38]

Note that children and adolescents who received the shorter 6-month intensive regimen for TB meningitis do not receive continuation phase treatment.[38]

Patients with MDR-TB should have their final regimen based on the results of drug-susceptibility testing, in consultation with a specialist.

Primary options

isoniazid: children: 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

Consider – corticosteroid

Back
ACUTE
|
active TB: non-pregnant, HIV-negative
|
drug resistance not suspected
Consider – 

corticosteroid

Additional treatment recommended for SOME patients in selected patient group

Corticosteroids may be used in limited situations. Adjunctive corticosteroid therapy has been shown to attenuate the inflammatory response in TB meningitis and result in improved survival.[101][102] [ Cochrane Clinical Answers logo ]

The American Thoracic Society (ATS)/Centers for Disease Control and Prevention (CDC)/Infectious Diseases Society of America (IDSA) and WHO guidelines recommend initial adjunctive corticosteroid therapy with dexamethasone or prednisolone tapered over 6-8 weeks for patients with tuberculous meningitis.[48][94]​ The British Infection Society recommends that, in children, the initial dose of dexamethasone should be given for 4 weeks, then tapered over 4-8 weeks.[53]

Limited evidence suggests there may be a mortality benefit for use of corticosteroids in TB pericarditis without HIV infection.[104]​ Currently, the ATS/CDC/IDSA guideline suggests that adjunctive corticosteroid therapy should not be routinely used in patients with TB pericarditis but may be appropriate for selected patients who are at the highest risk for inflammatory complications, including those with large pericardial effusions, high levels of inflammatory markers, or signs of constriction.[48] The WHO recommends that adjunctive corticosteroid therapy may be used in tuberculous pericarditis.[94]

Consult local guidelines for dosing information as dose regimens vary.

Primary options

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

and

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

1st line – antituberculous therapy

Back
ACUTE
|
active TB: non-pregnant, HIV-negative
|
isoniazid resistance
1st line – 

antituberculous therapy

Drug-resistance may be suspected on the basis of historical or epidemiological information. 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 pulmonary TB, US and World Health Organization (WHO) guidelines recommend treatment with a 6-month regimen of rifampicin, ethambutol, pyrazinamide, and a later-generation fluoroquinolone.​[91][97]​ The WHO guidelines note that this regimen is likely to be effective in patients with extrapulmonary TB, but that no data are available for patients with exclusive extrapulmonary isoniazid-resistant TB.[97]

Consultation with an appropriate specialist is recommended to determine the most appropriate antituberculous therapy and supportive care.

1st line – antituberculous therapy

Back
ACUTE
|
active TB: non-pregnant, HIV-negative
|
multidrug resistance
1st line – 

antituberculous therapy

Multidrug-resistant (MDR) TB is defined as resistance to isoniazid and rifampicin, with or without resistance to other first-line drugs. Extensively drug-resistant (XDR) TB is defined as resistance to at least isoniazid and rifampicin, as well as any fluoroquinolone and either bedaquiline or linezolid (or both).[98]​ Pre-XDR-TB is resistance to isoniazid, rifampicin, and any fluoroquinolone.

The treatment regimen should be based on the results of drug susceptibility testing. Specific regimens should be selected by a specialist in the treatment of MDR TB.[97] The total number of TB medicines to include in the regimen needs to balance expected benefit with risk of adverse effects and non-adherence when the pill burden is high. Treatment of MDR-TB and rifampicin-resistant (RR) TB/RR-TB meningitis should be guided by knowledge of TB medicines that cross the blood-brain barrier.[97]

Patients with rifampicin-resistant (RR) TB are also eligible for treatment with MDR TB regimens.[97] Short (6 or 9 months) and longer (18 months or more) regimens are included in the WHO guidelines for the treatment of people with drug-resistant TB.[97] The WHO short-course regimens are a major step forward for low- and middle-income settings where access to second-line drug susceptibility testing may not be available. In places with the ability to check second-line drug sensitivities, creation of an appropriate regimen would be based on drug susceptibilities. The short-course regimens may expose patients to drugs that are not indicated.

The 6-month all-oral regimen is composed of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM).[97][99][100]​ The WHO recommends the use of this 6-month regimen for adults and adolescents aged 14 and over with confirmed pulmonary TB and all forms of extrapulmonary TB (except for TB involving the CNS, osteoarticular and disseminated [miliary] TB), regardless of HIV status, who have less than 1 month exposure to bedaquiline, linezolid, pretomanid, or delamanid. The WHO suggests that this regimen is used where appropriate rather than the 9-month or longer MDR/RR-TB regimens.[97] If the patient has documented resistance to fluoroquinolones, the WHO advises that the regimen should continue without moxifloxacin (BPaL); although initiation of BPaLM should not be delayed while waiting for results of drug susceptibility testing.

The 9-month all-oral regimen is recommended by the WHO for patients who have extrapulmonary TB that is not severe, where severe disease is defined as miliary TB or TB meningitis, or in children aged less than 15 years defined as extrapulmonary forms of disease other than lymphadenopathy (peripheral nodes or isolated mediastinal mass without compression).[97] It is recommended over the longer MDR/RR-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 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), and this is followed by 5 months of treatment with levofloxacin/moxifloxacin, clofazimine, ethambutol, and pyrazinamide.[97] Two months of linezolid may be used in place of the 4 months of ethionamide. The WHO recommends the use of the 9-month regimen for adults and children without extensive pulmonary TB disease, regardless of HIV status, and who have less than 1 month exposure to bedaquiline, fluoroquinolones, ethionamide, linezolid, and clofazimine.[97]

Longer MDR TB regimens last 18 months or more and may be standardised or individualised; regimens are designed to include a minimum number of medicines considered to be effective based on patient history or drug-resistance patterns.[97] This longer-term regimen is recommended for all patients with extrapulmonary TB who do not fulfil the criteria for the shorter-term regimens; however, adjustments may be required, depending on the specific location of the disease.[97] 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.[97]

Group A (include all three medicines): levofloxacin or moxifloxacin; bedaquiline; linezolid.

Group B (add one or both medicines): clofazimine; cycloserine or terizidone.

Group C (add to complete the regimen and when medicines from Groups A and B cannot be used): ethambutol; delamanid; pyrazinamide; imipenem/cilastatin or meropenem; amikacin or streptomycin; ethionamide or prothionamide; aminosalicylic acid.

active TB: non-pregnant, HIV-positive

1st line – intensive phase therapy

Back
ACUTE
|
active TB: non-pregnant, HIV-positive
|
drug resistance not suspected
1st line – 

intensive phase therapy

Treatment of TB in HIV-positive patients follows the same general principles as in other patients with TB. However, there are some additional considerations, including the potential for drug interactions, especially between rifampicin and antiretrovirals (non-nucleoside reverse-transcriptase inhibitors and protease-inhibitors). For this reason, rifabutin may be considered as an alternative to rifampicin.[48] Dosage should be adjusted as necessary.

Patients with TB and HIV infection should receive antiretroviral therapy (ART) during antituberculosis treatment. World Health Organization (WHO) guidelines recommend that ART is started as soon as possible within 2 weeks of starting TB treatment, regardless of CD4 cell count, unless the patient has TB meningitis (when ART is delayed for 4-8 weeks).[94]

The antituberculous therapy is given once-daily on 5 days per week by directly observed therapy (DOT) during the intensive phase with the weekend/holiday doses self-administered.[48] All medications are administered together.

Initial intensive-phase treatment involves the first-line drugs of isoniazid, rifampicin, pyrazinamide, and ethambutol, for 2 months with drug-susceptibility testing for those agents.[48][94] After 2 months, the continuation phase is started.

WHO guidelines recommend that children aged between 3 months and 16 years with non-severe TB (defined as peripheral lymph node TB; intrathoracic lymph node TB without airway obstruction; 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.[38][94] Ethambutol should be included in areas of high prevalence of HIV or isoniazid resistance.[38][94] Children and adolescents who do not meet the criteria for non-severe TB should receive the standard 6-month treatment regimen (including ethambutol) or extended treatment regimens for severe forms of extrapulmonary TB.[38][94]

TB medications should be administered daily; intermittent twice-weekly administration is not recommended for HIV-infected patients. The preferred method for HIV patients is daily DOT.[48]

Pyrazinamide is not recommended for patients experiencing acute gout as it further elevates uric acid levels. Older patients (age >75 years) may not tolerate pyrazinamide and providers may consider leaving it out of treatment regimens.[48]​ Patients who do not receive pyrazinamide during the intensive phase should receive 7 months of continuation phase (to give 9 months of total treatment).

Regimens may need to be modified in patients with hepatic injury or renal insufficiency; a specialist should be consulted for guidance on choice of regimen and appropriate doses. Several TB medications are metabolised by the liver and may potentially cause or exacerbate hepatic injury. Mild hepatitis may require only closer monitoring without changes in the standard regimen. However, severe hepatitis while on TB treatment may make it necessary to hold medications and use an alternate liver-sparing regimen. Dose adjustments may be required in patients with renal insufficiency or end-stage renal disease.[48]

As there is increased risk of retrobulbar neuritis resulting from ethambutol toxicity in patients with renal failure, particular attention to testing of visual acuity/colour discrimination and counselling of patients is also required in this population.

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

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: non-pregnant, HIV-positive
|
drug resistance not suspected
Plus – 

continuation phase therapy

Treatment recommended for ALL patients in selected patient group

Treatment of TB in HIV-positive patients follows the same general principles as in other patients with TB. However, there are some additional considerations, including the potential for drug interactions, especially antiretrovirals. For this reason, rifabutin may be considered as an alternative to rifampicin. Dosage should be adjusted as necessary.

Patients with TB and HIV infection should receive antiretroviral therapy (ART) during antituberculosis treatment. World Health Organization guidelines recommend that ART is started as soon as possible within 2 weeks of starting TB treatment, regardless of CD4 cell count, unless the patient has TB meningitis (when ART is delayed for 4-8 weeks).[94]

After 2 months of intensive phase treatment in patients with drug-susceptible EPTB, pyrazinamide and ethambutol are discontinued, and isoniazid and rifampicin are given for the continuation phase. Duration of the continuation phase depends on the site of infection and severity of disease. Generally, for EPTB that does not involve CNS or bones and joints, continuation phase therapy is given for 4 months (i.e., 6 months of total treatment). Total therapy for 9 months is considered for patients with extensive skeletal TB, especially when large joints are involved with slow clinical response. Patients with central nervous system (CNS) TB receive 7-10 months of continuation phase therapy (9-12 months total).[94]

Children aged 3 months to 16 years with non-severe TB should receive 2 months of continuation phase therapy (4 months total). Those with severe TB, other than TB meningitis or osteoarticular TB, and also children aged less than 3 months, should receive the standard 6-month treatment regimen.[94]

Children with osteoarticular TB or TB meningitis should receive 10 months of continuation phase therapy (12 months total).[38]

Patients with MDR-TB should have their final regimen based on the results of drug-susceptibility testing, in consultation with a specialist.

Primary options

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

OR

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

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

More

Consider – corticosteroid

Back
ACUTE
|
active TB: non-pregnant, HIV-positive
|
drug resistance not suspected
Consider – 

corticosteroid

Additional treatment recommended for SOME patients in selected patient group

Corticosteroids may be used in limited situations. Adjunctive corticosteroid therapy has been shown to attenuate the inflammatory response in TB meningitis and result in improved survival.[101][102] [ Cochrane Clinical Answers logo ]

The American Thoracic Society (ATS)/Centers for Disease Control and Prevention (CDC)/Infectious Diseases Society of America (IDSA) and WHO guidelines recommend initial adjunctive corticosteroid therapy with dexamethasone or prednisolone tapered over 6-8 weeks for patients with tuberculous meningitis.[48][94] ​US guidelines for the prevention and treatment of opportunistic infections in those with HIV recommend adjunctive treatment with dexamethasone for adults with TB involving the CNS, though notes that studies involving those with HIV are limited.[92]​ One subsequent randomised controlled trial in adults with HIV infection and TB meningitis found that adjunctive dexamethasone did not reduce mortality over 12 months (death from any cause) compared with placebo.[103]​ US guidelines for the prevention and treatment of opportunistic infections in children with HIV recommend considering adjunctive corticosteroid treatment for those with TB meningitis.[93]​ The British Infection Society recommends that, in children, the initial dose of dexamethasone should be given for 4 weeks, then tapered over 4-8 weeks.[53]

Limited evidence suggests there may be a benefit for use of corticosteroids in TB pericarditis.[104]​ Currently, the ATS/CDC/IDSA guideline suggests that adjunctive corticosteroid therapy should not be routinely used in patients with TB pericarditis but may be appropriate for selected patients who are at the highest risk for inflammatory complications, including those with large pericardial effusions, high levels of inflammatory markers, or signs of constriction.[48] US guidelines for the prevention and treatment of opportunistic infections in those with HIV state that adjunctive corticosteroid therapy is not recommended in the treatment of adults and adolescents with TB pericarditis; however, it may be considered in children.[92][93]​​​ The WHO recommends that adjunctive corticosteroid therapy may be used in tuberculous pericarditis.[94]

Consult local guidelines for dosing information as dose regimens vary.

Primary options

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

OR

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

1st line – antituberculous therapy

Back
ACUTE
|
active TB: non-pregnant, HIV-positive
|
isoniazid resistance
1st line – 

antituberculous therapy

Drug-resistance may be suspected on the basis of historical or epidemiological information. 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 pulmonary TB, US and World Health Organization (WHO) guidelines recommend treatment with a 6-month regimen of rifampicin, ethambutol, pyrazinamide, and a later-generation fluoroquinolone.​[91][97]​ The WHO guidelines note that this regimen is likely to be effective in patients with extrapulmonary TB, but that no data are available for patients with exclusive extrapulmonary isoniazid-resistant TB.[97]

Consultation with an appropriate specialist is recommended to determine the most appropriate antituberculous therapy and supportive care.

1st line – antituberculous therapy

Back
ACUTE
|
active TB: non-pregnant, HIV-positive
|
multidrug resistance
1st line – 

antituberculous therapy

Multidrug-resistant (MDR) TB is defined as resistance to isoniazid and rifampicin, with or without resistance to other first-line drugs. Extensively drug-resistant (XDR) TB is defined as resistance to at least isoniazid and rifampicin, as well as any fluoroquinolone and either bedaquiline or linezolid (or both).[98]​ Pre-XDR-TB is resistance to isoniazid, rifampicin, and any fluoroquinolone.

The treatment regimen should be based on the results of drug susceptibility testing. Specific regimens should be selected by a specialist in the treatment of MDR TB.[97]​ The total number of TB medicines to include in the regimen needs to balance expected benefit with risk of adverse effects and non-adherence when the pill burden is high. Treatment of MDR-TB and rifampicin-resistant (RR) TB/RR-TB meningitis should be guided by knowledge of TB medicines that cross the blood-brain barrier.[97]

Patients with rifampicin-resistant (RR) TB are also eligible for treatment with MDR TB regimens.[97] Short (6 or 9 months) and longer (18 months or more) regimens are included in the WHO guidelines for the treatment of people with drug-resistant TB.[97] The WHO short-course regimens are a major step forward for low- and middle-income settings where access to second-line drug susceptibility testing may not be available. In places with the ability to check second-line drug sensitivities, creation of an appropriate regimen would be based on drug susceptibilities. The short-course regimens may expose patients to drugs that are not indicated.

The 6-month all-oral regimen is composed of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM).[97][99][100]​ The WHO recommends the use of this 6-month regimen for adults and adolescents aged 14 and over with confirmed pulmonary TB and all forms of extrapulmonary TB (except for TB involving the CNS, osteoarticular and disseminated [miliary] TB), regardless of HIV status, who have less than 1 month exposure to bedaquiline, linezolid, pretomanid, or delamanid. The WHO suggests that this regimen is used where appropriate rather than the 9-month or longer MDR/RR-TB regimens.[97] If the patient has documented resistance to fluoroquinolones, the WHO advises that the regimen should continue without moxifloxacin (BPaL); although initiation of BPaLM should not be delayed while waiting for results of drug susceptibility testing.

The 9-month all-oral regimen is recommended by the WHO for patients who have extrapulmonary TB that is not severe, where severe disease is defined as miliary TB or TB meningitis, or in children aged less than 15 years defined as extrapulmonary forms of disease other than lymphadenopathy (peripheral nodes or isolated mediastinal mass without compression).[97] It is recommended over the longer MDR/RR-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 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), and this is followed by 5 months of treatment with levofloxacin/moxifloxacin, clofazimine, ethambutol, and pyrazinamide.[97] Two months of linezolid may be used in place of the 4 months of ethionamide. The WHO recommends the use of the 9-month regimen for adults and children without extensive pulmonary TB disease, regardless of HIV status, and who have less than 1 month exposure to bedaquiline, fluoroquinolones, ethionamide, linezolid, and clofazimine.[97]

​Longer MDR TB regimens last 18 months or more and may be standardised or individualised; regimens are designed to include a minimum number of medicines considered to be effective based on patient history or drug-resistance patterns.[97] This longer-term regimen is recommended for all patients with extrapulmonary TB who do not fulfil the criteria for the shorter-term regimens; however, adjustments may be required, depending on the specific location of the disease.[97] 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.[97]

Group A (include all three medicines): levofloxacin or moxifloxacin, bedaquiline, linezolid.

Group B (add one or both medicines): clofazimine; cycloserine or terizidone.

Group C (add to complete the regimen and when medicines from Groups A and B cannot be used): ethambutol; delamanid; pyrazinamide; imipenem/cilastatin or meropenem; amikacin or streptomycin; ethionamide or prothionamide; aminosalicylic acid.

active TB: pregnant

1st line – referral to specialist

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active TB: pregnant
1st line – 

referral to specialist

Expert consultation is obtained. Antituberculous therapy is initiated based on clinical suspicion after optimal diagnostic samplings.

While awaiting that information, an expanded empiric regimen may be used. The final regimen will be based on the results of drug-susceptibility testing.

Use of pyrazinamide in pregnant women is controversial due to lack of detailed teratogenicity data, but it should be considered in patients with EPTB, particularly when HIV co-infection is present. Patients who do not receive pyrazinamide during the intensive phase should receive 7 months of continuation phase (to give 9 months of total treatment).

All medications should be administered together.

Intensive phase should continue for 2 months, with the ultimate duration to be determined on the basis of eventual drug susceptibilities and expert consultation.[48]

Treatment of drug-resistant TB, especially multidrug-resistant (MDR) TB, should be attempted only with expert advice.

Drug-resistance may be suspected on the basis of historical or epidemiological information. MDR isolates are resistant to at least both isoniazid and rifampicin.​[91][97]​​

Consult a specialist for guidance on choice of regimen and doses.

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