Tuberculosis treatment
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Persons with tuberculosis (TB) infection (class 2 or class 4 TB), but who do not have TB disease (class 3 or class 5 TB), cannot spread the infection to other people. TB infection in a person who does not have TB disease is not considered a case of TB and is often referred to as latent TB infection (LTBI). This distinction is important because treatment options will be different for a person who has LTBI instead of active TB disease.
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Treatment of latent TB infection
Treatment of latent TB infection (LTBI) is essential to controlling and eliminating TB by reducing the risk that TB infection will progress to disease.
- Although the terms "preventive therapy" and "chemoprophylaxis" have been used for decades, they have also been confusing because it rarely results in true primary prevention of infection as with vaccinations. The terminology "treatment of LTBI" will hopefully promote greater understanding of the concept for both patients and providers, resulting in more widespread implementation of this essential TB control strategy.
Assessment to rule out active TB is necessary before treatment for LTBI is started.
Candidates for treatment of LTBI are those very high-risk groups with positive tuberculin of 5 mm or more as well as those high-risk groups with skin test 10 mm or more.
There are several treatment regimens available:
- Isoniazid (INH) for 9 months (270 daily doses taken within 12 months) is the optimal regimen. (93% effective)
- Isoniazid for 6 months (180 daily doses within 9 months) might be adopted by a local TB program based on cost-effectiveness and patient compliance. The shorter regimen is not recommended for children or persons with radiographic evidence of prior tuberculosis (old fibrotic lesions). (69% effective)
- A twice-weekly regimen for the above 2 treatment regimens is an alternative if administered under Directly observed therapy (DOT).
- Rifamin only for 4-months (120 daily doses within 6 months) is an alternative for those who are unable to take isoniazid or pyrazinamide.
- Rifampin and pyrazinamide is no longer recommended for treatment of LTBI (but is still useful in active TB). (See References Updates).
Treatment Regimen Chart adopted from Table 10 of Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection (see References)
Since about 10 percent of latent TB infection progresses to active TB disease, the 9 month INH treatment regimen reduces the 10 percent risk to less than 1 percent while the 6 month INH treatment reduces it to 3 percent. Treatment is recommended to prevent infecting others and reducing death rates (50 percent if untreated). Currently TB disease kills 2 million people each year mostly in developing countries.
Close contacts
Close contacts are those sharing the same household or other enclosed environments. Those most at risk are children under 4 years of age, immunosuppressed people, and others who may develop TB disease quickly after infection. Close contacts who have had a negative tuberculin skin test reaction (less than 5 mm of induration) should be retested 10 to 12 weeks after they were last exposed to TB. Treatment of LTBI may be discontinued if the skin test result is again negative and if the person is no longer exposed to TB. However, immunosuppressed persons, including those with HIV disease, should complete the course of LTBI treatment regardless of the skin test reaction.
Children and adolescents
Children less than 4 years of age are at greater risk of having their infection progress to disease and to develop life-threatening forms of TB. These close contacts should receive treatment for LTBI even if the tuberculin skin test and chest X-ray do not suggest TB, because infected infants may be anergic as late as 6 months of age.
A second tuberculin test should be placed 10 to 12 weeks after the last exposure to infectious TB. Treatment can be discontinued if it is also negative.
Treatment of active TB disease
The current accepted first-line therapy is a combination of the drugs rifampicin, isoniazid (INH), pyrazinamide, and ethambutol. After two months, the number of drugs is reduced. A typical treatment for a standard (i.e. non-drug resistant) strain of TB is 2HRZE / 4HR (= two months of INH, rifampin, pyrazinamide and ethambutol followed by four months of Rifampin and INH). The number of relapses is about 2-3% this way. Medication can be given two or three times per week (different/higher dosages) with the same results as daily therapy.
Why four drugs? If only one drug is given, what ends up happening is that all the bacteria sensitive to that drug are killed and three months later, the patient will be infected with progeny of the bacteria that were resistant to that particular drug. Rifampicin and isoniazid are bactericidal agents that kill the bacteria, pyrazinamide acts well against the intracellular bacteria which are dormant inside macrophages and other cells, and ethambutol is a bacteriostatic agent that inhibits bacterial proliferation while the other drugs kill off the TB. Rifampin is the drug that provides the best "sterilization"; this means that it will kill dormant bacteria very well in order to lower the number of relapses after a successful treatment.
Streptomycin is used if the initial 4-drug therapy fails, often in conjunction with other second-line drugs such as capreomycin, cycloserine, new macrolides, quinolones, and protionamide. Streptomycin and capreomycin are not available as oral medications and must be injected. The newer linezolid (of the oxazolidinone class) has anti-mycobacterial activity in the laboratory, and is a promising drug to be evaluated in combination with others, either for those persons with intolerance to usual drugs, or for TB resistance to usual combinations.
Treatment monitoring
At least monthly, patients should be evaluated for adherence to the prescribed regimen, signs and symptoms of active TB disease or hepatitis.
Patients with TB disease should be monitored monthly until cultures convert to negative. After 3 months of medications, if cultures are positive or symptoms do not resolve, reevaluate for potential drug-resistant disease or nonadherence to drug regimen. If cultures do not convert to negative despite 3 months of therapy, consider initiating DOT.
DOTS or Directly Observed Treatment, Short-course is currently recommended by the World Health Organization (WHO). The mainstay of this is the DOT or Directly Observed Treatment portion which involves health care workers directly monitoring tuberculosis patients actually swallowing their anti-tuberculous therapy for at least the first two months of treatment. Treatment with properly implemented DOTS has a success rate exceeding 95% and prevents the emergence of further multi-drug resistant strains of tuberculosis.
Adverse drug reactions are expected in 20-25% of patients but only 5% of all patients will have a severe enough reaction to warrant a change in their drug regimen. Hepatic damage is the most significant of the drug reactions. Patients should immediately report any adverse reactions.
Baseline lab testing is not routinely indicated for all patients. Baseline liver function tests are indicated if there are risks for liver disease or if patient has HIV infection, or pregnant.
Peripheral neuropathy and CNS effects are associated with the use of isoniazid and is due to pyridoxine (vitamin B6) depletion, but is uncommon at doses of 5 mg/kg. Persons with conditions in which neuropathy is common (e.g., diabetes, uremia, alcoholism, malnutrition, HIV-infection), as well as pregnant women and persons with a seizure disorder, may be given pyridoxine (vitamin B6) (10-50 mg/day) with isoniazid.
- In busy clinics, because pyridoxine is inexpensive and relatively harmless, it is commonly given as a supplement to all patients to save time in verifying if a patient is at risk for neuropathy.
References
- Chan ED, Iseman MD. Current medical treatment for tuberculosis. BMJ 2002;325:1282-6 (fulltext).
- Treatment of Tuberculosis 2003 ATS/CDC/IDSA American Thoracic Society CDC Infectious Diseases Society of America, (fulltext,PDF format).
- Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection 2000 ATS/CDC (fulltext,PDF format) (Updates 2001-2003).
