Preventive Therapy

in patients who have a positive tuberculin (PPD intermediate) skin test and do not have active TB [latent TB infection (LTBI)]

Preventive therapy, or prophylactic therapy, for patients with latent TB infection (LTBI) who need therapy include:

  1. INH 300 mg po qd for 9 months – this is the best therapy for LTBI.
  2. INH 300 mg po qd for 6 months
  3. RIF 600 mg po qd for 4 months
  4. RIF 600 mg po qd and PZA 20 mg/kg po qd for 2 months

All these regimens require pretreatment liver chemistries and if PZA is given a pretreatment serum uric acid is needed.

RIF may be a problem in patients who are being treated for AIDS or HIV infection with protease inhibitors (PIs) and/or non-nucleotide reverse transcriptase inhibitors (NNRTIs)
(See HIV Drug Interactions ).

Multiple drugs are always prescribed in the treatment of active TB, and prophylaxis for latent TB infections can be treated with single drugs:

The bacterial load (population) of an active tuberculous lesion varies from 107 to 109 (infiltrate versus cavity). Since

  • 1 in 105 mycobacterium is a naturally occurring mutant resistant to INH
  • 1 in 106 mycobacterium is a naturally occurring mutant resistant to RIF
  • 1 in 1013 mycobacterium is a naturally occurring mutant resistant to both INH and RIF
it is obvious that multiple drug treatment is needed for active TB.

When a latent TB infection (LTBI) is present, the bacterial load is smaller than when active TB is present. Therefore, single drug therapy is adequate because the mycobacterial population is often 10 to 103. In these small populations of mycobacteria, naturally occurring mutants resistant to INH or RIF are very rare or non-existent.

Bacillus of Calmette and Guerin (BCG) vaccination:

BCG is a vaccine derived from a strain of bovine mycobacteria and is used in countries in which there is a high incidence of active TB.

It is usually given as preventive therapy to young people with a negative PPD and is believed to protect those who are vaccinated from developing overwhelming TB and dying of their disease.

Due to the use of varied vaccines throughout the world, the efficacy of the vaccine is variable. A proper BCG vaccination will result in a positive PPD. Since a positive PPD test due to BCG vaccination or a new infection with TB cannot be differentiated, patients who test positive on a PPD skin test should all be considered for INH preventive therapy.

The problem of INH-associated hepatitis:

Approximately 10 to 20% of INH recipients develop elevated liver enzymes. Most patients with mild subclinical hepatic damage do not progress to overt hepatitis and recover completely even while continuing INH therapy.

In contrast, continuation of INH in patients with clinical symptoms may result in severe hepatocellular toxicity, which is associated with a higher fatality rate than that of patients in whom INH was discontinued immediately.

The risk of death from TB is estimated to be 11 times higher than the risk of death from INH hepatitis.

The development of INH hepatitis has been linked to several factors including

  • acetylator phenotype
  • age
  • daily alcohol consumption
  • concurrent rifampin use.

The mechanisms underpinning INH hepatotoxicity remain unclear and may be multifactorial. Age and concurrent alcohol use are the most significant factors to consider.

Progressive liver damage is rare in persons less than 20 years of age. It occurs in 0.3% of persons between 20 to 34, in 1.2% of patients between 35 and 49, and 2.3% of persons over 50.

Whether biochemical monitoring of liver function is of value in the detection of liver toxicity secondary to INH is controversial. The American Thoracic Society and the CDC do not recommend routine LFT’s unless symptoms suggest hepatitis. However, of 1000 patients receiving INH, 47 of 64 patients with extremely high AST levels were asymptomatic. Similar findings have been found in 5 of 83 health care workers receiving INH preventive therapy.

Accordingly, many physicians favor monthly LFT monitoring particularly in high-risk patients. High risk patients are

  • 35 or more years of age
  • consume alcohol dailytakeother hepatotoxic drugs (particularly
    • rifampin
    • HIV protease inhibitors
    • acetaminophen)
  • intravenous drug abusers
  • black and hispanic women
  • all post partum women
  • all those with preexisting liver disease
INH should be discontinued if the AST levels exceed 3 to 5 times the normal value.

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