Summary. Preventive therapy substantially reduces the risk that TB infection will progress to disease. Certain groups are at very high risk of developing TB disease once infected. Persons in these groups should be considered candidates for preventive therapy, regardless of their age. In addition, infected persons younger than 35 years of age in high-prevalence groups should be given priority for preventive therapy. The current preventive therapy regimen is 6 to 12 months of daily isoniazid. Patients must be monitored monthly (or more frequently, if necessary) for symptoms of adverse reactions, as well as for their adherence to the prescribed regimen. In instances of known exposure to drug-resistant organisms, alternative preventive therapy regimens may be recommended. New, short-course preventive regimens are currently being evaluated.
Persons in the following high-risk groups should be given high priority for preventive therapy if they have positive skin test results, regardless of their age (the criterion for a positive reaction, in millimeters of induration, is given in parentheses):
In addition, in the absence of any of the preceding risk factors, persons younger than 35 years of age in the following high-prevalence groups should be evaluated for preventive therapy if their reaction to the tuberculin skin test is 10 mm or greater:
Persons younger than 35 years of age with no known risk factors for TB should be evaluated for preventive therapy if their reaction to the tuberculin test is 15 mm or greater. This group should be given a lower priority for prevention efforts than the groups already listed.
Persons who may have occupational exposure to TB (e.g., health care workers and staff of nursing homes, drug treatment centers, or correctional facilities) should be considered for preventive therapy if they have a positive tuberculin reaction. The appropriate cutoff for defining a positive reaction depends on the employee's individual risk factors for TB and on the prevalence of TB in the facility (see Screening for TB Disease and Infection).
Isoniazid preventive therapy is not recommended for infected persons who are 35 years of age or older unless these persons are at high risk of developing TB disease. This is because the risk of isoniazid-related hepatitis outweighs the benefits of preventive therapy in this age group.
Close contacts with an initial tuberculin reaction of <5 mm should receive a chest radiograph and should be considered for preventive therapy in any of the following situations:
Close contacts who have a negative reaction to an initial skin test should be retested 10 weeks after they were last exposed to TB. Preventive therapy may be discontinued if the skin test result is again negative and if the person is no longer being exposed to TB. However, persons known to have or suspected of having HIV infection should be given preventive therapy regardless of their skin test reaction if anergy is demonstrated and their risk of infection is judged to be high.
Infants who are exposed to a person with TB disease should be evaluated with a tuberculin skin test and a chest radiograph. If the skin test result is negative and the chest radiograph is normal, the infant should be skin tested again at 3 to 4 months and at 6 months. The infant should receive preventive therapy even if the tuberculin skin test result and chest radiograph do not suggest TB, because infected infants may be anergic as late as 6 months of age. Isoniazid can be discontinued if the skin test result is negative at 6 months, provided that at least 10 weeks have passed since the infant was last exposed to infectious TB.
Generally, pregnant women who are found to be tuberculin positive upon routine screening should not be given preventive therapy until after delivery. However, pregnant women who are likely to have been recently infected or who have high-risk medical conditions, especially HIV infection, should be given isoniazid preventive therapy as soon as TB infection is documented and TB disease has been ruled out. Tuberculin skin testing is both safe and reliable throughout the course of pregnancy.
Preventive therapy may not be an option for all persons who have positive skin test results. Persons for whom preventive therapy might not be indicated include
Clinicians should educate these persons about TB infection and disease and advise them to seek medical evaluation immediately if any symptoms of TB disease develop.
Clinical trials have shown that daily isoniazid preventive therapy for 12 months reduces the risk for TB disease by more than 90% in infected patients who complete a full course of therapy. There is evidence that 6 months of preventive therapy with isoniazid also confers a high degree of protection (approximately 69% in patients who complete the regimen) against the progression of TB infection to TB disease. Every effort should be made to ensure that patient adhere to preventive therapy for at least 6 months. Children should receive at least 9 months of preventive therapy. HIV-infected persons should receive 12 months of isoniazid preventive therapy.
Isoniazid is normally used alone for preventive therapy in a single daily dose of 300 mg in adults and 10 to 15 mg/kg body weight in children, not to exceed 300 mg per dose.
For persons who are at especially high risk for TB and whose adherence is questionable, directly observed preventive therapy should be considered. This method of treatment is especially appropriate in institutions and facilities where preventive therapy can be observed by a staff member. Isoniazid can be given two times a week at a dosage of 15 mg/kg as directly observed preventive therapy. Data on the effectiveness of intermittent isoniazid preventive therapy are limited. However, the results of studies of twice-weekly therapy with isoniazid suggest that it is an effective form of preventive therapy in adults and children.
For patients who have a positive tuberculin skin test result and either silicosis or a chest radiograph demonstrating old fibrotic lesions and who have no evidence of current disease, acceptable regimens include either 4 months of isoniazid plus rifampin or 12 months of isoniazid, provided that infection with drug-resistant organisms is judged to be unlikely.
For close contacts of infectious patients who have isoniazid-resistant TB, preventive therapy with rifampin should be considered. Therapy should last at least 6 months for adults and 9 months for children, and the usual therapeutic dose should be given. In addition, a rifampin-based preventive therapy regimen should be considered for isoniazid-intolerant patients. However, if a patient is unlikely to be infected with an isoniazid-resistant strain of M. tuberculosis and can tolerate isoniazid, preventive therapy with isoniazid should be used.
For persons likely to have been infected with M. tuberculosis resistant to both isoniazid and rifampin, observation without preventive therapy is usually recommended because only isoniazid and rifampin have been evaluated for preventive therapy. However, for persons at an especially high risk for TB disease once infected (e.g., persons with HIV infection), preventive therapy with an alternative regimen should be strongly considered.
Alternative regimens should include at least two drugs to which the infecting organism has demonstrated susceptibility. Potential alternative regimens include either 6 months of daily ethambutol and pyrazinamide or 6 months of pyrazinamide and one of the quinolones (ofloxacin or ciprofloxacin), in the usual therapeutic doses. Careful assessment to rule out the possibility of TB disease is necessary before preventive therapy is started. Patients treated with an alternative regimen should be followed for 2 years.
New, short-course preventive therapy regimens (e.g., rifampin and pyrazinamide for 2 months and rifampin alone for 4 months) are currently being evaluated.
Before preventive therapy is started, clinicians should:
When isoniazid is used alone to treat persons with TB disease, resistance to isoniazid is likely to develop. For this reason, persons suspected of having TB disease should receive multidrug treatment until the diagnosis is confirmed or ruled out. If previous (not current) TB is diagnosed, multidrug treatment should continue for 4 months for adults and for 6 months for children.
At least once a month, clinicians should evaluate patients receiving preventive therapy for
At follow-up visits, patients should routinely be asked about adherence. Pill counts should be taken routinely, and urine test may periodically be used to check for the presence of isoniazid metabolites. However, urine tests indicate only whether isoniazid was taken in the preceding 24 hours.
Peripheral neuropathy is associated with the use of isoniazid but is uncommon at doses of 5 mg/kg. Persons with conditions in which neuropathy is common (e.g., diabetes, uremia, alcoholism, malnutrition), as well as pregnant women and persons with a seizure disorder, may be given pyridoxine (10-50 mg/day) with isoniazid. As little as 6 mg/day of pyridoxine has been shown to prevent isoniazid-associated neuropathy.
Persons who are considered at high risk for hepatotoxicity should have a measurement of serum glutamic-oxaloacetic transaminase (SGOT or AST) before starting therapy and monthly during the course of therapy. Measurements of hepatic enzymes are not recommended for persons younger than 35 years of age unless the patient is at risk for adverse reactions due to isoniazid preventive therapy.
Because of a high risk for adverse reactions to isoniazid, special precautions are recommended for persons who
Some evidence suggests that women, particularly black and Hispanic women, are at increased risk for fatal hepatitis associated with isoniazid. This risk may also be increased during the postpartum period. These persons should be closely monitored for adverse reactions throughout the course of treatment.
About 10% to 20% of persons taking isoniazid will have some mild, asymptomatic elevation of liver enzymes. These abnormalities tend to resolve even if isoniazid is continued. If any of the measurements exceeds three to five times the upper limit of normal or if the patient reports symptoms of adverse reactions, the discontinuation of isoniazid should be strongly considered.
Patients should be educated about the symptoms of hepatitis and other adverse reactions to isoniazid, and they should be advised to report immediately to the clinician if any of these symptoms occur during preventive therapy. In addition, clinicians should advise all patients who start preventive therapy to report immediately any symptoms of TB disease.
Dispense no more than a 1-month supply of medicine at a time.