Activity of Pyrazinamide in the Guinea Pig Model of Tuberculosis

Ordway et al. (8) have recently evaluated standard chemo-therapy with a combination of rifampin, isoniazid, and pyrazi-namide (PZA) in the guinea pig model of tuberculosis (TB) and described long-term bacterial persistence. Soon after the introduction of PZA in 1952, perhaps the most experienced group examining the activity of antituberculosis drugs in the guinea pig model reported that PZA had little or no activity (9). In the two guinea pig experiments they describe, estab-lished tuberculosis was treated, starting 21 or 30 days after infection with strain H37Rv, with about 150 mg PZA/kg of body weight twice daily by gavage for periods of 75 or 100 days. Deaths occurred in 3 of 22 untreated control animals and in 5 of 20 PZA-treated animals, with total organ macroscopic scores of 10.8 and 13.5 (controls) and 9.2 and 9.6 (PZA), while a group treated with isoniazid (5 mg/kg/day) intramuscularl