Abstract

Pyrazinamide is an important antimycobacterial drug used in the contemporary short-course therapy of tuberculosis. Pyrazinamide is similar to isoniazid in its narrow spectrum of clinically-relevant antibacterial activity, which essentially includes only M. tuberculosis. The drug is bactericidal to slowly metabolizing organisms located within the acidic environment of the phagocyte or caseous granuloma; it is active only at a pH of ca. 6.0. Pyrazinamide is considered a prodrug and is converted by the tubercle bacillus to the active form pyrazinoic acid. The clinical recognition that the inclusion of pyrazinamide (PZA) allowed a reduction in the duration required to achieve predictable cures has revolutionized tuberculosis chemotherapy. PZA has been found to accelerate the time required to achieve culture negativity and to yield ca. 95% cure rates in 6 months when combined with isoniazide and rifampicin. Thus the short-course regimens have been implemented worldwide as the golden standard for management of tuberculosis and remained unchanged for decades. The most frequently recommended and effective combination is isoniazid, rifampicin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid and rifampicin for 4 months. The presented review gives a concise outline of the biochemical, pharmacological and clinical features of pyrazinamide as a first line antituberculous drug.