Bactericidal and sterilizing activities of antituberculosis drugs during the first 14 days
Bactericidal and sterilizing activities of antituberculosis drugs during the first 14 days
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DOI：
10.1164/rccm.200210-1125oc
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发表时间：
2003-05-15
影响因子：
24.7
通讯作者：
Mitchison, DA
中科院分区：
文献类型：
--
作者：
Jindani, A;Doré, CJ;Mitchison, DA
对100例单独或联合使用异烟肼、利福平、吡嗪酰胺、乙胺丁醇或链霉素等22种治疗方案的患者，每隔2天对痰中结核分枝杆菌的菌落形成单位进行计数。通过对数计数的线性回归系数测量了菌落形成单位在最初的2天快速药物决定杀灭阶段和随后的12天慢得多的灭菌活动期间的指数下降。前2天的回归系数因药物的不同而有显著差异；多元回归分析中影响最大的是异烟肼（p < 0.001）和利福平（p = 0.027）。异烟肼的快速杀伤效果不受加入其他药物的影响，因此，在异烟肼中加入未知药物后活性的变化是无法测量的。对2 ~ 14天的系数进行多元回归分析，利福平和链霉素的影响显著（p值分别为0.007和0.006），说明两种药物都具有重要的杀菌活性，其中链霉素的作用更早。异烟肼和吡嗪酰胺对患者无显著影响。仅在联合用药方案的分析中，乙胺丁醇与利福平的作用方向相反（p = 0.01），表明乙胺丁醇可以拮抗其他药物的杀菌活性。
Colony-forming units of Mycobacterium tuberculosis in sputum were counted at 2-day intervals in 100 patients treated with 22 regimens of isoniazid, rifampin, pyrazinamide, ethambutol, or streptomycin, given alone or in combinations. The exponential fall in colonyforming units was measured by linear regression coefficients of the log counts during the initial 2-day phase of rapid, drug-determined killing and during the subsequent 12 days of much slower sterilizing activity. The regression coefficients during the first 2 days varied significantly according to the drug; the greatest effects in multiple regression analyses were due to isoniazid (p < 0.001) and rifampin (p = 0.027). The rapid kill obtained with isoniazid was unaffected by addition of other drugs, so that a change in activity after adding an unknown drug to isoniazid would not be measurable. In multiple regression analysis of the coefficients during Days 2-14, rifampin and streptomycin had significant effects (p = 0.007 and 0.006, respectively), indicating that both drugs had important sterilizing activity, streptomycin particularly early. Isoniazid and pyrazinamide had no significant effects. In analyses of combined drug regimens only, ethambutol had an effect (p = 0.01) in reverse direction to that of rifampin, suggesting it antagonized the sterilizing activity of other drugs.