Tuberculosis Organism-Specific Therapy 

Updated: Feb 16, 2016
  • Author: Thomas E Herchline, MD; Chief Editor: Michael Stuart Bronze, MD  more...
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Diagnostic Studies and Therapeutic Regimens

Provided below are recommendations for diagnostic testing for tuberculosis as well as first-line, second-line, and alternative treatment regimens; treatment recommendations for extrapulmonary and for latent disease; special considerations; and monitoring parameters.

See Tuberculosis: Diagnostic Imaging and Treatment Challenges, a Critical Images slideshow, to help determine the best approach for patients with this multisystemic disease.

Appropriate cultures

See the list below:

  • Tuberculosis is caused by Mycobacterium tuberculosis, and attempts should be made to culture respiratory secretions from all persons with suspected tuberculosis
  • When possible, sputum should be collected in the early morning on 3 consecutive days
  • In hospitalized patients, sputum can be collected every 8h to obtain information more quickly
  • In persons unable to spontaneously produce sputum for culture, other methods for obtaining a respiratory specimen include the following: sputum induction via inhalation of hypertonic saline; gastric lavage (used primarily in young children); and bronchoscopy with bronchial washings
  • In the appropriate clinical setting, mycobacterial cultures should be obtained from pleural fluid, lymph nodes, cerebrospinal fluid, or any other tissue that is clinically suspected of involvement
  • DNA-based tests provide rapid identification of tuberculosis; DNA probes are approved for direct testing on smear-positive or smear-negative sputa [1]

Other diagnostic testing

See the list below:

  • Human immunodeficiency virus (HIV) testing should be performed in all patients with tuberculosis and an unknown HIV status
  • Drug susceptibility testing for all first-line medications should be obtained
  • Tuberculin skin testing (TST) (purified protein derivative [PPD] skin test; Mantoux test) is used primarily to diagnose latent tuberculosis infection (LTBI); TST has limited sensitivity in screening for active tuberculosis
  • Whole-blood assay based on interferon-gamma release (IGRA) is an alternative to TST

TST interpretation:

Cut-offs for interpreting the TST are based on tuberculosis risk factors.

Wheal ≥ 5 mm:

  • Close contacts to persons with tuberculosis
  • Persons with HIV infection or other significant immunosuppression
  • Persons with apical radiographic abnormalities that are suspicious for tuberculosis

Wheal ≥ 10 mm:

  • Patients with underlying medical conditions such as diabetes, end-stage renal disease, or severe malnutrition
  • Recent immigrants from countries with high tuberculosis incidence
  • Recent converters (within 2y)
  • Employees or residents of institutional settings, including hospitals, nursing homes, homeless shelters, and correctional facilities

Wheal ≥ 15 mm (with none of the above risk factors):

  • Whole-blood assay based on interferon-gamma release (IGRA)
  • Available tests include QuantiFERON-TB GIT and T-SPOT.TB
  • Sensitivity and specificity are similar to TST
  • Antigens used for the IGRA tests do not cross-react with BCG

First-line treatment recommendations (pulmonary disease)

Initial-phase therapy [2, 3, 4] :

  • Tuberculosis is caused by organisms that are resistant to isoniazid; therefore, a 4-drug regimen is necessary in the initial phase

Generally, all adults with previously untreated tuberculosis should get 2-mo initial-phase therapy of the following:

  • Isoniazid (INH) 5 mg/kg/day (maximum [max] 300 mg/day, 10 mg/kg/day in children) PO plus
  • Rifampin (RIF) 10 mg/kg/day (max 600 mg/day, 15 mg/kg/day in children) PO plus
  • Pyrazinamide (PZA) 25 mg/kg/day (max 2 g/day, 35 mg/kg/day in children per World Health Organization [WHO] guidelines, 15-30 mg/kg/day in children per Centers for Disease Control and Prevention [CDC] guidelines) PO plus
  • Ethambutol (EMB) 15 mg/kg/day (max 1.6 g/day, 20 mg/kg/day in children) PO

If PZA cannot be included in the initial phase of treatment, or if the isolate is resistant to PZA alone (an unusual circumstance), the initial phase should consist of INH, RIF, and EMB given daily for 2mo; examples of circumstances in which PZA may be withheld include severe liver disease, gout, and, perhaps, pregnancy.

Duration of therapy:

  • The initial phase may be given daily for 2wk and then twice weekly for 6wk, or 3 times weekly throughout
  • For patients receiving daily therapy, EMB can be discontinued as soon as the results of drug susceptibility studies demonstrate the isolate is susceptible to INH and RIF
  • For drug-susceptible tuberculosis, INH, RIF, PZA, and EMB are given until susceptibilities become available; then, EMB can be discontinued
  • Regardless of the initial therapy, the continuation phase is 4mo with INH plus RIF based on clinical parameters

Intermittent dosing (only for use in patients on directly observed therapy [DOT]) [4] :

  • INH 20 mg/kg (max 900 mg) PO 3 times weekly plus
  • RIF 10 mg/kg (max 600 mg) PO 3 times weekly plus
  • PZA 35 mg/kg (max 3000 mg) PO 3 times weekly plus
  • EMB 30 mg/kg (max 2800 mg) PO 3 times weekly

Second-line treatments (for drug-resistant tuberculosis or intolerance to first-line drugs)

See the list below:

Continuation-phase therapy

See the list below:

  • Treatment should be based on chest x-ray and sputum culture results after 2-mo initial-treatment phase

No cavitation on chest x-ray:

  • If negative sputum culture: INH 5 mg/kg/day (max 300 mg/day, 10 mg/kg/day in children) PO plus  RIF 10 mg/kg/day (max 600 mg/day, 15 mg/kg/day in children) PO for 4mo or
  • INH 5 mg/kg/day (max 300 mg/day, 10 mg/kg/day in children) PO plus  rifapentine 300 mg PO once a week for 4mo, which is a treatment option only for nonpregnant, HIV-negative adults without cavitary or extrapulmonary disease who are smear-negative at 2mo
  • If positive sputum culture: INH 5 mg/kg/day (max 300 mg/day, 10 mg/kg/day in children) PO plus  RIF 10 mg/kg/day (max 600 mg/day, 15 mg/kg/day in children) PO for 4mo or
  • INH 5 mg/kg/day (max 300 mg/day, 10 mg/kg/day in children) PO plus rifapentine 300 mg PO once a week for 7mo, which is a treatment option only for nonpregnant, HIV-negative adults without cavitary or extrapulmonary disease who are smear-negative at 2mo

Cavitation on chest x-ray [4] :

  • If negative sputum culture: INH 5 mg/kg/day (max 300 mg/day, 10 mg/kg/day in children) PO plus RIF 10 mg/kg/day (max 600 mg/day, 15 mg/kg/day in children) PO for 4mo
  • If positive sputum culture: INH 5 mg/kg/day (max 300 mg/day, 10 mg/kg/day in children) PO plus RIF 10 mg/kg/day (max 600 mg/day, 15 mg/kg/day in children) PO for 7mo

Duration of therapy:

  • The continuation phase is given for either 4 or 7mo; the 4-mo treatment is more commonly prescribed
  • The 7-mo continuation phase is recommended for 3 groups: (1) patients with cavitary pulmonary tuberculosis caused by drug-susceptible organisms and whose sputum culture obtained at the time of completion of 2mo of treatment is positive; (2) patients whose initial phase of treatment did not include PZA; and (3) patients being treated with once weekly INH and rifapentine and whose sputum culture obtained at the time of completion of the initial phase is positive
  • The continuation phase may be given daily, 2 times weekly by DOT, or 3 times weekly by DOT

Alternative-treatment recommendations

See the list below:

  • Intermittent regimens with rifapentine may be considered for selected patients to avoid relapse or to avoid rifamycin resistance (patients who are HIV positive should not receive rifapentine)
  • Rifapentine may be used once weekly with INH in the continuation phase (rifapentine 10 mg/kg [max 600 mg] PO once weekly plus INH 15 mg/kg [max 900 mg] PO once weekly); rifapentine 600 mg PO twice weekly (induction phase)
  • Rifabutin can be used as a substitute for rifampin; the recommended dose of rifabutin is 5 mg/kg (max 300 mg) PO daily
  • Streptomycin has been shown to be as effective as EMB; general dosing recommendations of streptomycin are 15 mg/kg (max 1000 mg) IM or IV daily given 5-7 times a week and reduced to 2-3 times a week after the first 2-4mo or after culture conversion; streptomycin 10 mg/kg IM or IV is recommended in persons > 59y

Treatment recommendations for extrapulmonary disease

See the list below:

  • Principles used in the treatment of pulmonary tuberculosis also apply to extrapulmonary tuberculosis [5]
  • Treatment with INH and RIF is preferred for a duration of 6mo for most cases of extrapulmonary disease—except for bone and joint disease, which is generally treated for 6-9mo, and neurotuberculosis, which is generally treated for 9-12mo [5]

Treatment of latent tuberculosis

See the list below:

  • INH 300 mg PO daily for 9mo [3] or
  • RIF 600 mg PO daily for 4 mo [3] or
  • INH 900 mg PO plus  rifapentine 900 mg PO once-weekly for 12 weeks (must be administered as directly observed therapy) [6, 7] ; use weight-based dosing for adults who weigh < 50 kg or children aged 2-11 y
  • Patients diagnosed with LTBI should have a significant reaction to TST or have a positive blood assay; active tuberculosis should be ruled out [3]

Special considerations

See the list below:

  • PZA can be given at the usual dose with mild to moderate renal impairment, but the dosing needs to be reduced in patients with severe renal impairment; generally avoid use of PZA during pregnancy, unless the patient has HIV or drug-resistant tuberculosis
  • Dosing for streptomycin must be adjusted with any degree of renal impairment and should not be given during pregnancy
  • EMB dosing should be decreased with mild to moderate renal impairment; EMB should generally be avoided in patients with severe renal impairment
  • Many of the drugs used to treat tuberculosis are potentially hepatotoxic; increased monitoring of hepatic signs and symptoms is important
  • Liver enzymes should be monitored at least monthly and more often in patients with severe hepatic impairment; liver enzymes must be monitored at least monthly in patients on tuberculosis therapy
  • Renal function should be checked periodically in patients on medications requiring dose adjustments for renal insufficiency
  • Hospitalized patients with suspected or documented tuberculosis must be placed in appropriate isolation; this includes a private room with negative pressure and adequate air exchanges; persons entering the room must wear masks or respirators capable of filtering droplet nuclei
  • Regimens for the treatment of persons coinfected with HIV and tuberculosis must account for the numerous potential drug-drug interactions between antiretroviral and antituberculosis medications

Monitoring parameters

See the list below:

  • Sputum smear and culture should be assessed every 2-4wk until negative
  • Therapy should be extended to 9mo if the patient has cavitary disease and remains culture-positive after 2mo of treatment
  • Chest radiographs should be reassessed in patients who are not improving clinically
  • Serum uric acid should be monitored in patients who require long-term PZA therapy
  • Patients who are receiving long-term EMB therapy should undergo periodic visual acuity and red-green color-perception testing