Mehta J B, Shantaveerapa H, Byrd R P, Morton S E, Fountain F, Roy T M
Veterans Affairs Medical Center, Mountain Home, TN 37684-4000, USA.
Chest. 2001 Nov;120(5):1520-4. doi: 10.1378/chest.120.5.1520.
The standard daily dose of rifampin in directly observed treatment of Mycobacterium tuberculosis (TB) is 600 mg, taken orally. The purpose of this study was to assess the efficacy of standard dose rifampin therapy in patients who were slow to respond to routine directly observed therapy (DOT).
Patients with non-drug-resistant pulmonary TB who were receiving 600 mg of oral rifampin by DOT were eligible for inclusion. Patients were deemed slow to respond if their sputum smears and cultures remained positive for M tuberculosis and if the patient's condition did not improve clinically or radiographically after 3 months of treatment. Serum rifampin levels were ascertained to determine the adequacy of the standard rifampin dosing. Patients with subtherapeutic blood levels had their rifampin dose increased to 900 mg, and rifampin levels were repeated. Rifampin dosage was increased again if blood levels were still subtherapeutic. No antitubercular medications were added to the treatment regimen. The total weekly dose of the other standard treatment drugs was not increased.
Of 124 new patients with active pulmonary TB, 6 patients were identified as slow to respond to the standard antitubercular DOT. All six patients had subtherapeutic serum rifampin levels. All six patients responded clinically, radiographically, and mycobacteriologically after an increase in rifampin dosage to reach target drug blood level.
Standard dosing with rifampin resulted in a poor clinical response and subtherapeutic serum levels in six patients. Increasing the dosage of rifampin improved the outcome without additional side effects. In TB patients who are slow to respond to standard treatment, an inadequate dose of rifampin should be suspected. Current antituberculer drug administration does not include adjusted dosage for rifampin.
在直接观察治疗结核分枝杆菌（TB）时，利福平的标准日剂量为口服600毫克。本研究的目的是评估标准剂量利福平疗法对常规直接观察治疗（DOT）反应迟缓患者的疗效。
接受600毫克口服利福平DOT治疗的非耐药性肺结核患者符合纳入条件。如果患者的痰涂片和培养物中结核分枝杆菌仍呈阳性，且在治疗3个月后患者的病情在临床或影像学上没有改善，则认为该患者反应迟缓。测定血清利福平水平以确定标准利福平剂量是否充足。血药水平低于治疗水平的患者将利福平剂量增加至900毫克，并再次检测利福平水平。如果血药水平仍低于治疗水平，则再次增加利福平剂量。治疗方案中不添加其他抗结核药物。其他标准治疗药物的每周总剂量不增加。
在124例新的活动性肺结核患者中，有6例被确定为对标准抗结核DOT反应迟缓。所有6例患者的血清利福平水平均低于治疗水平。在将利福平剂量增加至达到目标血药水平后，所有6例患者在临床、影像学和细菌学方面均有反应。
利福平标准剂量治疗导致6例患者临床反应不佳且血清水平低于治疗水平。增加利福平剂量可改善治疗结果且无额外副作用。在对标准治疗反应迟缓的结核病患者中，应怀疑利福平剂量不足。目前的抗结核药物给药方案中不包括利福平的调整剂量。
