Tuberculosis: 9. Treatment.

Effective tuberculosis (TB) control in Canada depends on case-finding to discover infectious cases, investigation of contacts of those with TB, appropriate treatment (with drugs to which the organisms are susceptible and user-friendly regimens to encourage adherence), case holding (which includes registration of the patient and methods of ensuring that patients take their medications until they are declared cured by the appropriate health officials) and treatment of latent infection in high-risk groups. In this article I review the theoretical basis for treatment and describe a number of accepted regimens. Antituberculosis drugs have been described in terms of their activity in 3 areas: bactericidal activity, sterilizing activity and prevention of drug resistance. Bactericidal activity is the ability of a drug to reduce the number of actively dividing bacilli during the induction (initial) phase of therapy. Isoniazid is the most potent bactericidal antituberculosis agent, although rifampin and streptomycin also have some bactericidal activity. Sterilizing activity is the ability of a drug to kill semidormant bacteria. Rifampin and pyrazinamide are the most potent sterilizing drugs for TB. Drug resistance* is prevented by drugs that eliminate all bacterial populations and do not allow the emergence of resistant organisms. Effective treatment regimens are divided into 2 phases: an initial or induction phase, during which agents are used in combination to kill rapidly multiplying populations of Mycobacterium tuberculosis and to prevent the emergence of drug resistance, followed by a continuation phase, during which sterilizing drugs are used to kill the intermittently dividing populations. Adherence to the treatment regimen can be achieved by directly observed therapy (DOT), in which a health care provider watches the patient swallow each dose of medication. DOT is important in the treatment of tuberculosis because it allows for monitoring of the number of doses that an individual has taken, drawing attention immediately to those who have missed treatment and thus alerting the health care worker in charge of the particular case that the patient may be absconding from treatment. In addition, it ensures that monotherapy does not occur, which might happen if an individual is intolerant to one or more of the medications prescribed and thus consciously takes fewer of the drugs than necessary. It also allows for the extension of treatment on the basis of the number of doses missed. DOT may be given daily or intermittently (2 or 3 times a week). Intermittent therapy was introduced when it was shown in controlled clinical trials that therapeutic serum levels of the various antituberculosis drugs were maintained even when medications were given only 2 or 3 times a week. Intermittent regimens have proven effective, do not have more toxic effects than daily regimens and allow drug administration to be adapted to local conditions. All intermittent regimens must involve DOT. Education