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Treatment of TB: Primary Care Tools for the Management of TB

Author(s): J. Carey Jackson, MD; David Roesel, MD

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Treatment of TB

Why treat latent TB?

Completing a course of treatment decreases the person's lifetime risk of developing active TB by 90%. Treatment of latent TB is also a cornerstone of efforts to eliminate TB in society, since it minimizes the number of infectious cases.

Who should be treated for latent TB?

  • In general, anyone with a positive TB test who is at high risk of reactivation should be treated, regardless of age. (See above list of high-risk groups).
  • Although the 2000 CDC guidelines seem to suggest that foreign-born persons not be treated if they have been living in the United States more than 5 years, a recent study found that 25% of all cases of active TB in the US occur in this population. Treating all foreign-born people with latent TB should be strongly considered, regardless of when they immigrated.
  • Children who are close contacts to a case of infectious tuberculosis should be started empirically on treatment for latent TB. A baseline tuberculin skin test should be placed at the time of initiation of treatment, and repeated 10-12 weeks after the exposure. If the second test is negative and the child is over 6 months old, treatment can then be discontinued. A similar approach is recommended for HIV-infected patients.
  • Prior to treatment, active disease must be ruled out by means of a thorough history, physical examination, and chest radiograph. Sputum examination for acid fast bacilli is indicated if there is an abnormal chest radiograph or respiratory symptoms. Unexplained fevers, chills, night sweats, fatigue, or weight loss should prompt a search for extra-pulmonary TB if the chest radiograph is normal.

How is latent TB treated?

Preferred Regimen           

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Isoniazid 300 mg daily x 9 months

  • Nine months of isoniazid (INH) is the preferred treatment regimen for all cases of latent TB, including HIV patients, pregnant women, and children. A minimum of 270 doses must be administered within 12 months.
  • In pregnancy, it is preferable to wait until the post-partum period to administer INH, unless the mother has HIV or a recent contact with active TB. Breastfeeding is not a contraindication to isoniazid.
  • Supplementation with 10-50 mg/day of Pyridoxine (vitamin B6), is recommended for use in the following instances:
    • During pregnancy, lactation, and the post-partum period.
    • In people with seizures.
    • In conditions with increased risk of peripheral neuropathy: diabetes, HIV, alcoholism, renal failure, and malnutrition

Alternative Regimen

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Isoniazid 900 mg twice weekly x 9 months
              (directly-observed therapy)
Isoniazid 300 mg daily x 6 months
Isoniazid 900 mg twice weekly x 6 months
              (directly-observed therapy)
Rifampin 600 mg daily x 4 months

  • Six months of isoniazid is a more cost-effective regimen for latent TB, although nine months provides better protection from active disease (90% vs. 70% risk-reduction).
  • Directly-observed isoniazid therapy should be considered for persons at high risk who are suspected of nonadherence.
  • Courses of INH shorter than nine months do not provide adequate treatment in patients with HIV infection, and should not be used.
  • Rifampin is an acceptable alternative for those patients who cannot tolerate isoniazid. It cannot be used in patients taking protease inhibitors or non-nucleotide reverse transcriptase inhibitors. (Rifabutin 300 mg/day may be substituted). Rifampin causes orange coloration of tears, urine, and sweat, and may discolor contact lenses. It also causes increased sun sensitivity.

Not Recommended

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Rifamin plus pyrazinamide x 2 months

•  This regimen has been associated with an increased risk of severe hepatic injury and death, and should generally not be used.

Pediatric doses:

  • Isoniazid 10-15 mg/kg/day for 9 months
  • Isoniazid 20-40 mg/kg twice weekly for 9 months
  • Rifampin 10-20 mg/kg/day for 6 months

What sort of monitoring is needed during treatment?

  • The CDC recommends monthly clinic visits during treatment to assess adherence and identify signs or symptoms of adverse drug reactions. Treatment should be held if the patient develops anorexia, nausea, vomiting, abdominal pain, dark urine, jaundice, rash, persistent fatigue, easy bruisability, or paresthesias of the hands and feet. Patients should be advised to refrain from alcohol ingestion during treatment.
  • Hepatitis is the most important adverse effect of latent TB treatment. It usually occurs within the first three months of treatment, and people with advanced age or daily alcohol consumption are at greatest risk. Overall incidence of hepatotoxicity is 0.1% with isoniazid and 0.6% with rifampin.
  • Peripheral neuropathy is another known adverse effect of isoniazid. The incidence is under 0.2%, and those at highest risk are pregnant and breastfeeding women, diabetics, alcoholics, HIV patients, and patients with uremia. Pyridoxine supplementation should be provided to these high-risk groups.
  • Cutaneous reactions occur in up to 6% of people taking rifampin. They are generally self-limited. Thrombocytopenia is a rare complication of rifampin therapy.
  • Baseline laboratory testing and periodic laboratory monitoring are not routinely indicated during treatment of latent TB. Exceptions are the following:
    • Patients with chronic liver disease (including active hepatitis B or C)
    • Heavy drinkers of alcohol
    • HIV infected patients
    • Pregnant women
    • Post-partum women for the first three months after delivery
      These persons should ALT, AST, and bilirubin measured before and during the course of treatment.
  • If hepatic transaminases exceed 3 times the upper limit of normal in asymptomatic patients, or 5 times the upper limit of normal in patients with symptoms, treatment should be withheld.

Important drug-drug interactions:

Isoniazid increases the levels of:

  • Phenytoin
  • Carbamazepine
  • Warfarin
  • Benzodiazepines

Aluminum-containing antacids reduce the absorption of isoniazid.

Rifampin is a potent inducer of hepatic microsomal enzymes, and decreases the levels of several medications, including:

  • Warfarin
  • Oral contraceptives
  • Anticonvulsants
  • Sulfonylureas
  • Digoxin
  • Opiates
  • Cyclosporine
  • Ketoconazole
  • Dapsone

What about HIV co-infection?

HIV infection is the greatest known risk factor for the progression of latent M. tuberculosis infection to active TB. In many African countries, 30-60% of all new TB cases occur in people with HIV, and TB is the leading cause of death globally for HIV-infected people. HIV infection is associated with a much higher risk of reactivation of latent TB, and a more rapid progression of disease. Whereas in HIV-negative people a positive TB skin test carries a 5-10% lifetime risk of reactivation, in HIV-positive people reactivation occurs at a rate of 5-7% per year.

The tuberculin skin test may provide false-negative results in HIV patients due to impaired cellular immunity. However, testing for cutaneous anergy by placing intradermal controls (such as Candida antigen) has not been shown to be of benefit, and is not recommended. The performance of INF-based assays such as QuantiFERON® -TB Gold not yet been established.

How would you treat contacts of people with multi-drug resistant TB?

Standard latent TB treatment regimens are unlikely to be effective in high-risk contacts of people with MDR-TB. Treatment should be guided by susceptibility testing of the index case, and expert consultation should be sought.

This information is excerpted from:
Latent TB: FAQ's by David J. Roesel, MD,
University of Washington/Harborview Medical Center, Seattle, WA.