Current status of antimicrobial agents in the treatment of pulmonary tuberculosis

Abstract

In the treatment of pulmonary tuberculosis three combinations of antituberculosis drugs, SM-PAS, SM-INH and INH-PAS, appear equally effective. Differences between them, however, may be evident upon completion of studies now in progress. If these regimens were equally effective, the selection of SM-PAS for initial therapy would leave INH, the more versatile of the two major drugs, in reserve for retreatment if it should become necessary. Drug resistance is effectively delayed by all three combinations of drugs, but the particular advantages, if any, of one combination over another in this respect have not yet been clarified. Toxicity of drugs is now a relatively unimportant consideration either in the selection of a regimen or in the duration of chemotherapy. Whatever regimen is employed, there is now general agreement that uninterrupted drug therapy should be continued for at least one year, or six to twelve months after a target point of (1) closure of all cavities, (2) persistently negative sputum cultures and (3) maximal resolution of lesions, has been achieved. However, the optimum duration of chemotherapy is not known. The changes in the morphology of tuberculous lesions following the use of drugs do not differ qualitatively from those occurring with other forms of therapy. However, resolution is prompt and predictable. Solid necrotic lesions are affected relatively little. Cavity closure is usually a process of their filling in with necrotic material, and potential bronchial communications can often be demonstrated between the filled-in cavity and the bronchial tree. Filled-in cavities are not healed in a morphologic sense and thus there may be a rationale for resecting them. Yet bacilli are non-viable in closed necrotic lesions in 85 to 95 per cent of resections. There is no general agreement, however, that such bacilli are in fact dead. In the meantime the interpretation of these bacteriologic data is bound to influence the indications for resection of closed necrotic lesions. The relationships between surgery and chemotherapy not only involve the interpretation of the morphology and bacteriology of closed necrotic lesions, but depend also upon whether the primary role in the treatment of pulmonary tuberculosis is given to chemotherapy or to surgery.