Treatment of pulmonary tuberculosis with isoniazid and pyrazinamide: experience in 114 cases.

Pyrazinoic acid amide, now commonly known under the name Pyrazinamide or PZA and in previous years as Aldinamide, is a nicotinic acid derivative chemically related to isonicotinic acid hydrazide, more commonly designated Isoniazid or INH. A review of the early laboratory studies of PZA is omitted because of space limitations. In brief these studies indicated PZA alone to be a drug of slight to moderate anti-tuberculous activity and to be potentially hepatotoxic. New impetus was given to further studies with PZA when it was demonstrated by McCune and TompsetV that the combination of PZA and INH together produced an antimicrobial action which was qualitatively different from that produced by any of the standard anti-tuberculosis drugs administered either singly or together. By the microbial enumeration technique these authors demonstrated that unlike previous anti-tuberculosis drugs used singly or in combination which produced a depressed but stabilized population of bacilli in the spleens of infected animals, with PZAINH treated animals, the census of the population of tubercle bacilli did not stabilize but instead continued to fall at a rapid rate until bacilli could no longer be detected in the spleens or lungs of any of the animals. Indeed, the effects produced by PZA-INH were of a much more eradicative type than those produced by other drugs, and conceivably, may have represented complete sterilization of the treated animals. Further confirmation of the unusual additive effects of PZA and INH was provided by the intracellular studies of 1\’Iackaness2 who showed that PZA and nicotinamid, which are almost devoid of tuberculostatic activity against tubercle bacilli grown under ordinary cultural condition, possessed a high level of activity against tubercle bacilli, strain H37Rv, grown in isolated rabbit monocytes in vitro. Compared with INH, PZA was found to have only a slow bactericidal effect upon intracellular bacilli under these conditions, but when combined with isoniazid, PZA resulted in an increase in the bactericidal effect of isoniazid.