Clinical aspects of TB

Treatment

Treatment programmes

b) Current policy

The World Health Organisation has defined the essential drugs for the treatment of tuberculosis as isoniazid, rifampicin, pyrazinamide, ethambutol and streptomycin. In Hong Kong the current policy of chemotherapy for adults with tuberculosis is a 6 month course of intermittent chemotherapy on an out-patient basis. Guidelines for the treatment of TB were prepared jointly by the TB Control Coordinating Committee (Department of Health) and the TB Subcommittee of the Co-ordinating Committee in Internal Medicine (Hospital Authority) and these were published in Sept 1996. These summarise the recommended treatment for pulmonary and extra-pulmonary TB, with additional advice on the management of different drug-resistant strains of TB. They also provide advice for the treatment of TB when combined with other medical conditons. These guidelines are based on published findings as well as local experience, and will be updated and modified as necessary from time to time.

For some patients (eg those with poor visual acuity), streptomycin (1g) may be used instead of ethambutol.

If a patient cannot tolerate the higher dosages given 3 times a week, the treatment can be changed to a daily regimen.

The bacteriologic basis of short-course chemotherapy for tuberculosis is best understood by considering distinct subpopulations of tubercle bacilli with different susceptibilities to antituberculosis drugs.

3 subpopulations of tubercle bacilli:

1. Rapidly dividing group of extracellular organisms: Found in areas where the pH is neutral to alkaline. This subpopulation is readily killed by isoniazid, rifampin, and streptomycin when given in bactericidal doses.

2. Subpopulation generally growing slowly, but with spurts of metabolic activity: Thought to exist in solid caseous material . Rifampin seems to be the most effective drug in killing these organisms that grow intermittently rather than continuously.

3. Intracellular slowly deviding organisms: Found within the acidic environment of macrophages where metabolic activity is also slow.

It has long been known that pyrazinamide is active in an acid environment, and, thus, it seems logical to assume that beneficial effects from pyrazinamide noted in clinical trials result from its ability to kill intracellular organisms.

Studies have shown that the combination of isoniazid and rifampin, whensupplemented by pyrazinamide in the initial 2 months, has a bacteriologic relapse rate of less than 2%.

In recent years fixed combination tablets have been developed. One formulation contains all three drugs isoniazid, rifampicin and pyrazinamide. One tablet is given per 10 kg body weight. These preparations may aid compliance because of the simplified drug formulation. It is, however, essential to use only those formulations with proven bioavailability especially in relation to rifampicin.

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