Crowle A J, Sbarbaro J A, May M H
Am Rev Respir Dis. 1986 Nov;134(5):1052-5. doi: 10.1164/arrd.1986.134.5.1052.
Pyrazinamide (PZA) is a unique antituberculosis drug because it is effective in vivo but not in mediums commonly used to culture tubercle bacilli. Consequently, it was employed to test the validity of an in vitro macrophage model of human tuberculosis for value as a correlate of clinical events. The drug was as active in the macrophage model as it was clinically, inhibiting virulent tubercle bacilli at concentrations at 20 micrograms/ml or higher. By contrast, it was ineffective in 7H9 bacteriologic culture medium, even at concentrations as high as 2,560 micrograms/ml. It could be either bacteriostatic or bactericidal against intramacrophage tubercle bacilli, depending on its concentration, the donor of the macrophages, and the length of exposure of the infected macrophages to the drug. The data presented suggest that the clinical effectiveness of PZA is determined by a complicated self-modulating sequence of interactions between it, tubercle bacilli, and host macrophages. Specific evidence was found that tubercle bacilli may replicate within human macrophages in non-acid-fast form, thus indicating that colony-forming unit counts are inherently more accurate than acid-fast bacilli counts in these experiments, and also suggesting that important changes in bacillary cell wall composition may occur among tubercle bacilli within infected human macrophages.
吡嗪酰胺（PZA）是一种独特的抗结核药物，因为它在体内有效，但在常用于培养结核杆菌的培养基中无效。因此，它被用于测试人类结核病体外巨噬细胞模型作为临床事件相关指标的有效性。该药物在巨噬细胞模型中的活性与临床活性相同，在浓度为20微克/毫升或更高时可抑制强毒结核杆菌。相比之下，它在7H9细菌培养基中无效，即使浓度高达2560微克/毫升。根据其浓度、巨噬细胞供体以及受感染巨噬细胞接触药物的时间长短，它对巨噬细胞内的结核杆菌可能具有抑菌或杀菌作用。所呈现的数据表明，PZA的临床有效性取决于它、结核杆菌和宿主巨噬细胞之间复杂的自我调节相互作用序列。有具体证据表明，结核杆菌可能以非抗酸形式在人类巨噬细胞内复制，因此表明在这些实验中，集落形成单位计数本质上比抗酸杆菌计数更准确，也表明在受感染人类巨噬细胞内的结核杆菌中，杆菌细胞壁组成可能发生重要变化。
