Tuberculosis disease in children: Treatment and prevention

INTRODUCTION — Issues related to treatment and prevention of tuberculosis (TB) disease (active TB) in children will be reviewed here [1-4].

Issues related to epidemiology, clinical manifestations, and diagnosis of TB disease in children are discussed separately. (See "Tuberculosis disease in children: Epidemiology, clinical manifestations, and diagnosis".)

Issues related to diagnosis and treatment of TB infection (latent TB) in children are discussed in detail separately. (See "Tuberculosis infection (latent tuberculosis) in children".)

TERMINOLOGY AND DEFINITIONS — TB terminology is inconsistent in the literature [5]. Relevant terms are defined in the table (table 1). Definitions for drug-resistant TB are summarized in the table (table 2).

GENERAL TREATMENT PRINCIPLES

●Clinical diagnosis – TB in children is often diagnosed clinically, without bacteriologic confirmation (particularly among children under five years of age), given the difficulty of establishing a definitive diagnosis. (See "Tuberculosis disease in children: Epidemiology, clinical manifestations, and diagnosis", section on 'Overview'.)

A clinical diagnosis of TB is strengthened in the setting of clinical and radiographic response to empiric treatment in a child with a positive test for TB infection (tuberculin skin test [TST] or interferon-gamma release assay [IGRA]).

●Drug susceptibility testing – Culture-based drug-susceptibility testing should be performed on initial isolates from each site of disease. In the setting of negative cultures, the drug susceptibility test results for isolates from a presumed source person (if known or available) should be used to guide treatment decisions.

●Nitrosamine impurities – In August 2020, the US Food and Drug Administration (FDA) announced detection of nitrosamine impurities in samples of rifampin and rifapentine [6]. Some such compounds have been implicated as possible carcinogens in long-term animal studies, with toxicity largely related to cumulative exposure.

We favor continued use of rifampin for treatment of TB in children if acceptable to the patient and family, as the risk of not taking rifampin likely outweighs any potential risk from nitrosamine impurities. This approach is concordant with US FDA and United States Centers for Disease Control and Prevention (CDC) recommendations.  

PULMONARY TB — Inpatients with pulmonary TB should be placed on airborne infection isolation. (See "Tuberculosis transmission and control in health care settings".)

Empiric treatment — Design of a treatment regimen strongly depends on understanding drug susceptibility of the child's or source person's isolate; efforts should be directed at obtaining this information as quickly as possible.

●Presumed drug-susceptible TB – Empiric treatment for presumed drug-susceptible TB should include standard four-drug therapy (isoniazid, rifampin, pyrazinamide, and ethambutol). (See 'Traditional regimen (≥6 months)' below.)

●Considerations for suspected drug-resistant TB

•Indications for empiric treatment – The decision to treat empirically for drug-resistant TB (ie, a regimen including second-line drugs – pending conventional, culture-based drug susceptibility data) depends on the severity of clinical illness (smear positivity, presence of cavitary disease, certain forms of extrapulmonary disease) and the degree of suspicion for drug-resistant TB (given epidemiologic factors) (table 3). Demonstration of rifampin resistance on the Xpert MTB/RIF test should prompt initiation of treatment for drug-resistant TB while awaiting results of conventional, culture-based drug susceptibility testing.

Children for whom an empiric treatment regimen for drug-resistant disease may be warranted include [7]:

-Children with treatment failure (acid-fast bacilli sputum culture positive after four months of therapy, assuming drug sensitivity testing is not available, or poor response to traditional therapy)

-Children with relapse (recurrent TB after apparent cure)

-Children with exposure to an individual with infectious drug-resistant pulmonary TB

-Children with residence in or travel to a region with high prevalence of drug-resistant TB (see "Epidemiology and molecular mechanisms of drug-resistant tuberculosis", section on 'Epidemiology')

The approach to regimen selection is discussed below. (See 'Drug-resistant TB' below.)

•Clinical approach – Options for empiric treatment for drug-resistant disease include an expanded regimen (six or more drugs) or an abbreviated bedaquiline-containing regimen. Some clinicians may choose to start with an expanded regimen, with de-escalation once susceptibility data are available (either from a specimen obtained from the child or from the presumed source person). (See 'Drug-resistant TB' below.)

Drug-susceptible TB

Regimen selection

●Our approach – The approach to regimen selection should be guided by patient age and clinical factors (algorithm 1):

•Age <3 months − For children age <3 months, we treat with the traditional six-month regimen (table 4 and table 5).

•Age 3 months to 11 years − For children age 3 months to 11 years with nonsevere, smear-negative, presumed drug-susceptible disease, we treat with the shortened (four-month) regimen (table 4 and table 5). (See 'Shortened (four-month) regimen for nonsevere, smear-negative disease' below.)

For children in this age group who do not meet criteria for the shortened regimen, we treat with the traditional six-month regimen.

•Age 12 to 16 years − For children age 12 to 16 years with nonsevere, smear-negative, presumed drug-susceptible disease, we treat with the shortened (four-month) regimen. (See 'Shortened (four-month) regimen for nonsevere, smear-negative disease' below.)

For children in this age group who do not meet criteria for the shortened regimen, options include the traditional regimen for six months or the rifapentine-moxifloxacin-based regimen for four months (table 6).

While some TB clinicians favor the rifapentine-moxifloxacin-based regimen given the shorter duration, others favor the traditional six-month regimen pending further outcome data with the rifapentine-moxifloxacin-based regimen. Additional factors warranting consideration in selection of the rifapentine-moxifloxacin-based regimen (including screening for risk of QT prolongation as well as other contraindications and infrastructure requirements) are discussed separately. (See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection", section on 'Rifapentine-moxifloxacin-based four-month regimen'.)

•Age 17 to 18 years − For children age 17 to 18 years, options include the traditional six-month regimen or the four-month rifapentine-moxifloxacin-based regimen (table 6).

While some clinicians favor the rifapentine-moxifloxacin-based regimen given the shorter duration, others favor the traditional regimen pending further outcome data with the rifapentine-moxifloxacin-based regimen. Additional factors warranting consideration in selection of the rifapentine-moxifloxacin-based regimen (including screening for risk of QT prolongation as well as other contraindications and infrastructure requirements) are discussed separately. (See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection", section on 'Rifapentine-moxifloxacin-based four-month regimen'.)

●Regimens – Regimens for treatment of TB disease in children include the traditional (≥6 months) regimen and two shortened regimens:

•Traditional six-month regimen – The traditional six-month regimen consists of isoniazid, rifampin, pyrazinamide, and ethambutol for eight weeks, followed by isoniazid and rifampin for 16 weeks, for most forms of TB (excluding TB meningitis and osteoarticular TB) (table 4 and table 5).

•Shortened four-month regimen (for nonsevere, smear-negative disease) – The shortened four-month regimen consists of isoniazid, rifampin, and pyrazinamide (with or without ethambutol, according to local guidelines) for eight weeks, followed by isoniazid and rifampin for eight weeks (table 4 and table 5).

•Rifapentine-moxifloxacin-based four-month regimen – The rifapentine-moxifloxacin-based four-month regimen consists of rifapentine, isoniazid, pyrazinamide, and moxifloxacin for eight weeks, followed by rifapentine, isoniazid, and moxifloxacin for nine weeks (table 6). This regimen is for drug-susceptible pulmonary TB, in the absence of extrapulmonary involvement.

Available regimens

Traditional regimen (≥6 months)

●Clinical approach – The empiric traditional regimen includes three or four drugs: rifampin, isoniazid, and pyrazinamide, with or without ethambutol. The regimen is outlined in the tables (table 4 and table 5) [2,3].

Phases include:

•Initiation phase – This two-month phase includes three or four drugs with the goal of reducing the mycobacterial burden rapidly.

•Continuation phase – This four-month phase includes rifampin and isoniazid to target elimination of persistent mycobacteria.

Issues related to administration logistics, monitoring, and efficacy for this regimen are discussed separately. (See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection", section on 'Traditional regimen (≥6 months)'.)

●Use of ethambutol – Use of ethambutol is warranted in the following circumstances:

•Unknown drug susceptibility data (for the patient or source case), in setting of risk for isoniazid resistance

•Presence of AFB smear-positive disease or extensive radiographic involvement

•Presence of extrapulmonary TB  

Ethambutol may be excluded if the child and/or source person is known to have pan-susceptible TB, in the absence of the above factors.

Shortened (four-month) regimen for nonsevere, smear-negative disease — The shortened (four-month) regimen is outlined in the tables (table 4 and table 5); it was endorsed by the World Health Organization (WHO) in 2022 for treatment of children between 3 months and 16 years of age with nonsevere, smear-negative, presumed drug-susceptible disease (defined as pulmonary TB confined to one lobe); exclusions include cavitary disease, miliary TB, complex pleural effusion, clinically significant airway obstruction, and peripheral lymph node involvement [2]. In settings where rapid molecular testing with Xpert MTB/RIF is available, a result of negative, very low, low, or trace positive may be used as a proxy for smear-negative disease. (See 'Regimen selection' above.)

The regimen was evaluated in the SHINE trial (Shorter Treatment for Minimal Tuberculosis in Children) which included 1204 children <16 years (median age 3.5 years) with nonsevere, smear-negative, presumed drug-susceptible TB (including 127 patients with HIV infection) in South Africa, Uganda, Zambia, and India [8,9]. Children were randomly assigned to treatment with a four-month regimen (as summarized above) or a traditional six-month regimen (which included a continuation phase of 16 weeks rather than 8 weeks).

The four-month regimen was found to be noninferior to the six-month regimen; the primary outcome (defined as treatment failure [extension, change, or restart of treatment or TB recurrence], loss to follow-up during treatment, or death by 72 weeks) was observed among 3 percent of patients in each group (adjusted difference -0.4 percentage points, 95% CI -2.2 to 1.5). Adverse events were comparable between the groups (occurring in approximately 8 percent of participants in each group); adherence and retention rates were high (94 and 95 percent, respectively).

Rifapentine-moxifloxacin-based four-month regimen — The rifapentine-moxifloxacin-based regimen is outlined in the table (table 6) [2,10,11]. It was endorsed by the WHO in June 2021, and the United States Centers for Disease Control and Prevention (CDC) issued guidance for use in February 2022 [2,11]. The regimen may be used for nonpregnant patients (age ≥12 years, body weight ≥40 kg) with drug-susceptible pulmonary TB, in the absence of extrapulmonary involvement. (See 'Regimen selection' above.)

Important considerations for use of this regimen include ensuring fluoroquinolone susceptibility testing and monitoring for toxicity. Issues related to administration logistics and monitoring for this regimen are discussed separately. (See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection", section on 'Rifapentine-moxifloxacin-based four-month regimen'.)

The study evaluating the rifapentine-moxifloxacin four-month regimen included 63 adolescents ≥12 years of age; a four-month regimen consisting of rifapentine, isoniazid, pyrazinamide, and moxifloxacin was found to be noninferior to a traditional six-month regimen consisting of rifampin, isoniazid, pyrazinamide, and ethambutol [10]. The data from this trial are discussed further separately. (See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection", section on 'Rifapentine-moxifloxacin-based four-month regimen'.)

Drug-resistant TB — Circumstances in which an empiric treatment regimen for drug-resistant disease may be warranted are outlined above. The regimens below are appropriate for confirmed drug-resistant TB and for empiric treatment of suspected drug-resistant TB. (See 'Empiric treatment' above.)

General principles

●Definitions – Definitions for drug-resistant TB are summarized in the table (table 2). Risk factors for drug-resistant TB are summarized in the table (table 3).

●All-oral treatment preferred – Whenever possible, it is desirable to design a regimen that avoids use of an injectable agent [12]. This is particularly true for very young children and those with mild TB disease (ie, those with good nutrition, mild forms of extrapulmonary disease, and the absence of cavitation on chest radiography and human immunodeficiency virus [HIV] infection) [13].

According to WHO guidance issued in 2021, bedaquiline and/or delamanid may be used to treat children and adolescents of all ages with multidrug-resistant (MDR)/rifampin-resistant TB [14]. This guidance enables all-oral treatment regimens for children and adolescents of all ages.

Data and clinical experience support the use of bedaquiline, linezolid, and fluoroquinolones in children [2,15].

●Use of bedaquiline – Development of a pediatric bedaquiline formulation is underway; in the meantime, the available tablet formulation may be mixed with soft food or dissolved in water for pediatric administration [16]. Ideally bedaquiline should be given with food to maximize absorption [2].

Coadministration of bedaquiline with efavirenz or lopinavir/ritonavir should be avoided. Coadministration of bedaquiline with efavirenz is associated with reduced bedaquiline levels; coadministration of bedaquiline with lopinavir/ritonavir is associated with increased bedaquiline levels [17].

●Use of delamanid – Guidance for use of delamanid in children ages 6 to 17 years was issued by the WHO in 2018 [18]. Dosing of delamanid in children between three and five years of age has become easier with the availability of a 25 mg dispersible formulation, indicated for children ≥10 kg [2,19]. WHO provides guidance for delamanid dosing for children between 3 to 10 kg; its expert panel concluded that the balance between desirable and undesirable effects probably favors its use [2]. In the United States use of delamanid is under Investigational New Drug (IND) status; it is approved in Europe, China, India, South Africa, and elsewhere.

Delamanid should administered separately in time (ideally one hour) from other medications, including other antituberculous drugs and antiretroviral agents. Ideally delamanid should be given with food to maximize absorption [2].

Approach to monoresistant or polyresistant TB — The approach to treatment of monoresistant or polyresistant TB is outlined separately. (See "Treatment of drug-resistant pulmonary tuberculosis in adults", section on 'Treatment of monoresistant TB' and "Treatment of drug-resistant pulmonary tuberculosis in adults", section on 'Treatment of polyresistant TB'.)

Approach to MDR-TB or XDR-TB — For most children with uncomplicated pulmonary MDR-TB or extensively drug-resistant (XDR)-TB, we suggest treatment with an abbreviated regimen (6 to 12 months). Abbreviated regimens include an all-oral bedaquiline-containing regimen (duration 9 to 12 months) or an abbreviated bedaquiline-containing regimen (for children ≥14 years; duration 6 months); the approach depends on patient age and available resources including access to drugs and susceptibility testing (algorithm 2) [2]. (See 'Abbreviated regimens' below.)

A longer, individualized regimen (all-oral regimen for at least 18 months) is warranted for patient groups without sufficient data for use of an abbreviated regimen and in settings with limited drug availability. Indications for a longer regimen include (see 'Longer, individualized regimen' below):

●Disseminated, meningeal, or central nervous system disease

●Advanced HIV infection (CD4 <50 cells/microL) and extrapulmonary disease

●Pregnancy

●Extensive (or advanced) TB disease, such as bilateral cavitary disease or extensive parenchymal damage on chest radiography

●Contraindication to one or more drugs in the shorter-course regimens; these include:

•Prior exposure to one or more agents in the regimen for more than one month (unless susceptibility to these drugs is confirmed)

•Confirmed resistance or suspected ineffectiveness to a drug in the regimen (except isoniazid resistance)

•Intolerance to a drug in the regimen or risk of toxicity due to drug-drug interactions

•One or more drugs in the regimen are unavailable

Children with none of the above indications may be treated with an abbreviated regimen.

Pediatric dosing of second-line antituberculous drugs is summarized in the table (table 7). Use of second-line antituberculous agents in children is complicated by the lack of pediatric formulations for most of these drugs, which can lead to under- or over-dosing.

Abbreviated regimens

Bedaquiline-based regimen (9 to 12 months) — The 9- to 12-month bedaquiline-based regimen is described separately. (See "Treatment of drug-resistant pulmonary tuberculosis in adults", section on 'Other bedaquiline-based regimens'.)

Abbreviated bedaquiline-containing regimens — Abbreviated bedaquiline regimens include:

●BPaL: A six-month, all-oral regimen of bedaquiline, pretomanid, and linezolid

●BPaLM: A six-month, all-oral regimen of BPaL plus moxifloxacin

These regimens may be used for children ≥14 years of age; further study is needed before they should be used for younger children. Evidence for use of these regimens is discussed separately. (See "Treatment of drug-resistant pulmonary tuberculosis in adults", section on 'Abbreviated regimens'.)

Longer, individualized regimen — The approach to creating a longer, individualized regimen is described separately (table 8). (See "Treatment of drug-resistant pulmonary tuberculosis in adults", section on 'Longer, individualized regimen'.)

●Choice of injectable agent – An all-oral regimen is preferred. If an injectable agent must be used, kanamycin and capreomycin (not available in the United States; limited availability elsewhere) are preferred; amikacin or streptomycin should be used in children only if (1) other options are not possible, (2) drug susceptibility testing confirms susceptibility, and (3) monitoring for both ototoxicity and nephrotoxicity can be performed [13]. Regular audiometry is critical for monitoring children receiving these drugs, given potential association between early hearing loss and diminished language acquisition [13].

●Monitoring – Children on treatment for drug-resistant TB should be monitored at least monthly for adherence, response to treatment (eg, sputum analysis for those with pulmonary TB), and potential adverse events. Drug toxicity is common; in one meta-analysis of children treated for MDR-TB, it was reported in 39 percent of cases [20]. Similarly, in the series from Peru, adverse effects occurred in 42 percent of cases, although no events required suspension of therapy for >5 days [21].

Role of surgery — Issues related to surgery for treatment of drug-resistant TB are discussed further separately. (See "Treatment of drug-resistant pulmonary tuberculosis in adults", section on 'Role of surgery'.)

Administrative logistics and follow-up monitoring

●Medication adherence – Individual case management with directly observed therapy is essential for all patients to ensure adherence and safety and to prevent emergence of drug resistance. This is discussed further separately. (See "Adherence to tuberculosis treatment", section on 'Directly or video observed therapy'.)

●Education – Caregivers should be educated about the manifestations of drug toxicity. As an example, signs and symptoms of hepatic toxicity include anorexia, nausea, vomiting, dark urine, icterus, rash, pruritus, fatigue, fever, abdominal discomfort (particularly right upper quadrant discomfort), easy bruising or bleeding, and arthralgias. Other adverse events are summarized in the table (table 7). Adverse drug events should prompt medication discontinuation and clinical evaluation.

●Follow-up evaluation – Patients should be monitored at least monthly to assess for adherence, treatment response (improvement in symptoms, weight gain, and growth) and adverse drug events. Medications should be weight-adjusted monthly.

●Laboratory monitoring – Drug-related hepatotoxicity is rare in children; routine laboratory monitoring is not warranted during treatment for drug-susceptible TB in the absence of underlying liver disease or development of symptoms suggestive of hepatotoxicity.

●Sputum monitoring – For patients with negative initial acid-fast bacilli (AFB) smear and culture, sputum monitoring is not necessary. For patients with positive initial sputum AFB smear or culture, we obtain monthly sputum AFB smear and culture until two consecutive samples are culture negative. If positive sputum AFB smear and/or culture persists after two months of therapy, drug susceptibility testing should be repeated.

●Radiographic monitoring – During and following treatment, hilar adenopathy may persist for two to three years and should not be considered a poor response to therapy. Therefore, a normal radiograph is not necessary to discontinue treatment, and normal follow-up radiographs for discontinuation of treatment are not necessary in the absence of clinical deterioration [3].

Repeat chest radiography is warranted for patients who are not improving on antituberculous treatment.

●Therapeutic drug monitoring – Routine therapeutic drug monitoring is not necessary; it may be useful in some circumstances such as malabsorption, risk for drug-drug interactions, renal insufficiency, diabetes mellitus, and poor response to first-line therapy with known or assumed susceptibility to first-line agents [22].

Treatment failure — Failure to respond to treatment based on bacteriologic, radiographic, and/or clinical findings (such as continued or worsening clinical symptoms, failure to gain weight or weight loss) should prompt careful review of the treatment regimen as well as assessment for adherence [2]. In addition, specimens for mycobacterial culture and drug susceptibility testing should be obtained.

The management approach may include adjusting the drug regimen and/or extending the duration of treatment; these decisions should be made in consultation with expert guidance.

EXTRAPULMONARY TB — The approach to treatment of extrapulmonary TB (regimen and duration) should be guided by the clinical presentation. (See related topics.)

Regimens for extrapulmonary TB are often similar to treatment of pulmonary TB; an important exception is central nervous system (CNS) TB; this is discussed separately. (See "Central nervous system tuberculosis: Treatment and prognosis".)

IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME — The term "immune reconstitution inflammatory syndrome" (IRIS) refers to paradoxical worsening of a preexisting infectious process with administration of treatment.

●Patients with HIV infection – Patients with HIV are at risk for IRIS in the setting of initiation of antituberculous therapy and/or ART [23,24]. This is discussed further separately. (See "Immune reconstitution inflammatory syndrome", section on 'Tuberculosis'.)

●Patients without HIV infection – Clinical deterioration consistent with IRIS has been observed among immunocompetent children receiving antituberculous therapy [25,26]. In one study including 115 immunocompetent children, 10 percent developed paradoxical worsening within 15 to 75 days (median 39 days) of starting TB treatment; affected children with paradoxical reactions tended to be younger (median age at diagnosis of 26 months versus 66 months) [26]. The most common manifestation was worsening of preexisting pulmonary lesions (75 percent of cases); in addition, 25 percent of those experiencing IRIS developed disease manifestations in new anatomic locations.

PATIENTS WITH HIV INFECTION — For patients with HIV infection and TB disease (in the absence of central nervous system [CNS] involvement) who are not yet receiving antiretroviral therapy (ART), ART may be initiated within two weeks of starting antituberculosis therapy [1,3,27,28].

For patients with HIV infection and CNS TB, the timing of ART initiation is discussed separately. (See "Central nervous system tuberculosis: Treatment and prognosis", section on 'Antiretroviral therapy'.)

Patients with HIV are at risk for immune reconstitution inflammatory syndrome. (See 'Immune reconstitution inflammatory syndrome' above.)

Issues related to treatment of TB in patients with HIV infection are discussed further separately. (See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults with HIV infection: Initiation of therapy" and "Treatment of pulmonary tuberculosis in adults with HIV infection: Follow-up after initiation of therapy" and "Treatment of drug-resistant pulmonary tuberculosis in adults" and "Treatment of drug-resistant pulmonary tuberculosis in adults", section on 'Patients with HIV infection'.)

OUTCOMES

●Drug-susceptible TB – Outcomes for children with drug-susceptible TB are generally favorable. In one study including more than 29,000 children in South Africa, <1 percent died during treatment and 89.5 percent were cured or completed treatment; increased mortality was observed in children <2 years of age and in children with HIV infection (adjusted hazard ratio 3.13 and 6.85, respectively) [29].

●Drug-resistant TB – Relatively high rates of treatment success have been achieved among children with MDR-TB [30-32]. In a systematic review and meta-analysis including 875 patients in 18 countries, the treatment success rate was 78 percent [32]. Among those with HIV infection, the treatment success rate was higher among those who received ART (82 versus 56 percent).

Use of bedaquiline, delamanid, or linezolid can improve outcomes in children with MDR-TB; in one study including 119 children (of whom 18 received one or more of these drugs), favorable outcome (successful treatment completion or documented microbial cure) was observed more frequently among those who received these agents than among those who received standard second-line drugs (94 versus 80 percent) [33].

TOOLS FOR PREVENTION — Tools for prevention of TB include:

●Bacille Calmette-Guérin (BCG) immunization (based on regional policy). (See "Prevention of tuberculosis: BCG immunization and nutritional supplementation", section on 'Groups to consider for BCG vaccination'.)

●Identification and treatment of TB infection (latent TB) – This is especially critical for those at high risk for progressing from TB infection to TB disease. (See "Tuberculosis infection (latent tuberculosis) in children".)

●Interventions to reduce transmission – Inpatients with pulmonary TB should be placed on airborne infection isolation; this and other aspects of infection control are discussed further separately. (See "Tuberculosis transmission and control in health care settings".)

●Contact investigation is an essential tool to identify recently infected individuals who, once properly diagnosed, would benefit from treatment (for TB infection or TB disease) to reduce transmission. (See "Tuberculosis disease in children: Epidemiology, clinical manifestations, and diagnosis", section on 'Contact tracing'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Diagnosis and treatment of tuberculosis".)

SUMMARY AND RECOMMENDATIONS

●Empiric treatment – For presumed drug-susceptible TB, empiric treatment consists of standard four-drug therapy (isoniazid, rifampin, pyrazinamide, and ethambutol). The decision to treat empirically for drug-resistant TB (pending drug susceptibility data) depends on the severity of illness and the degree of clinical suspicion for drug-resistant TB (table 3); patient groups for whom an empiric treatment regimen for drug-resistant disease may be warranted are summarized above. (See 'Empiric treatment' above.)

●Drug-susceptible TB – The approach to regimen selection should be guided by patient age and clinical factors (algorithm 1) (see 'Regimen selection' above):

•For children age 3 months to 16 years with nonsevere, smear-negative, presumed drug-susceptible disease, we suggest treatment with the shortened (four-month) regimen (table 4 and table 5) (Grade 2B). (See 'Shortened (four-month) regimen for nonsevere, smear-negative disease' above.)

•For children age <3 months, and for children age 3 months to 11 years who do not meet criteria for the shortened regimen, we suggest treatment with the traditional six-month regimen (table 4 and table 5) (Grade 2C). (See 'Traditional regimen (≥6 months)' above.)

•For children age 12 to 16 years who do not meet criteria for the shortened regimen, and for children age 17 to 18 years, options include the traditional six-month regimen or the four-month rifapentine-moxifloxacin-based regimen (table 6). While some favor the rifapentine-moxifloxacin-based regimen given its shorter duration, others favor the traditional regimen pending further outcome data with the rifapentine-moxifloxacin-based regimen in adolescents.

Additional factors warranting consideration in selection of the rifapentine-moxifloxacin-based regimen (including screening for risk of QT prolongation and other contraindications) are discussed separately. (See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection", section on 'Rifapentine-moxifloxacin-based four-month regimen'.)

●Drug-resistant TB – Definitions are summarized in the table (table 2).

•Monoresistant TB or polyresistant TB – The clinical approach varies depending on the pattern of drug resistance. Treatment options are discussed separately. (See "Treatment of drug-resistant pulmonary tuberculosis in adults", section on 'Treatment of monoresistant TB' and "Treatment of drug-resistant pulmonary tuberculosis in adults", section on 'Treatment of polyresistant TB'.)

•Multidrug-resistant (MDR)-TB or extensively drug-resistant (XDR)-TB – For most children with uncomplicated pulmonary MDR-TB or XDR-TB, we suggest treatment with an abbreviated regimen (6 to 12 months) (Grade 2C). Abbreviated regimens include an all-oral bedaquiline-containing regimen (duration 9 to 12 months) or an abbreviated bedaquiline-containing regimen (for children ≥14 years; duration 6 months); the approach depends on patient age and available resources including access to drugs and susceptibility testing (table 7 and algorithm 2). All-oral regimens should be used whenever possible.

A longer, individualized regimen (all-oral regimen for at least 18 months) is warranted for patient groups without sufficient data for use of an abbreviated regimen and in settings with limited drug availability. Indications for a longer regimen include (see 'Approach to MDR-TB or XDR-TB' above):

-Disseminated, meningeal, or central nervous system (CNS) disease

-Patients with advanced HIV infection (CD4<50 cells/microL) and extrapulmonary disease

-Pregnancy

-Extensive (or advanced) TB disease, such as bilateral cavitary disease or extensive parenchymal damage on chest radiography

-Contraindication to one or more drugs in the shorter-course regimens

The approach to creation of a longer, individualized regimen is discussed separately (table 8). (See "Treatment of drug-resistant pulmonary tuberculosis in adults", section on 'Longer, individualized regimen'.)