Principles of therapy for tuberculosis.

The therapeutic strategy for tuberculosis is based on some fundamental principles. First, the multi-drug approach to decrease resistant mutants. Second, the concept of two-phase therapy, with initial three-four drugs to rapidly decrease the microbial concentration and with two drugs in the remaining period. Short six-month regimens based on two-phase protocols at present represent the standard therapy for most patients. An application of reference, especially in cases of adequate compliance is the directly observed therapy (DOT) which allows intermittent two-three-week administrations. The initial therapeutic approach includes rifampicin, isoniazid and pyrazinamide in the first two months, with the addition of ethambutol or streptomycin in case of primary over 4% isoniazid resistance in the population. Subsequently, rifampicin and isoniazid are administered daily or intermittently as DOT. In HIV-positive patients, initially 4 drugs are administered for at least nine months as DOT wherever possible. Multidrug resistance (MDR) is clinically associated to some peculiar features as the higher frequency of cavitations, the persistent elimination of mycobacteria in the sputum, a more aggressive course with a higher mortality. In MDR-TB some factors should be considered: previous antituberculosis therapy, results of previous in vitro susceptibility tests, patients' compliance, modes of administration, patterns of susceptibility of the population of origin of the patient with suspected MDR-TB. While waiting for the results of susceptibility tests, the therapeutic regimen should include 5 to 6 or 7 drugs selected based on the patient's characteristics. Close monitoring should be performed combining close surveillance of clinical course with bacteriology.