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含吡嗪酰胺的六个月短程化疗用于肺结核的初始治疗

[Six-month short course chemotherapy containing pyrazinamide for initial treatment of pulmonary tuberculosis].

作者信息

Wada M, Yosiyama T, Yosikawa M, Ogata H, Sugie T, Nakasono T, Sugita H

机构信息

Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo.

出版信息

Kekkaku. 1994 Nov;69(11):671-80.

PMID:7837720
Abstract

From January 1991 to December 1992, 419 patients with pulmonary tuberculosis were initially treated at Fukujuji Hospital. Among them, 190 patients, who were younger than 80 years old and had pulmonary tuberculosis with cavities or infiltration of extension 2 or 3, and/or were sputum-smear positive, had been treated by 6-month short course regimen containing pyrazinamide, 2HRS(E)Z/4HRE. And were eligible for the evaluation of the clinical usefulness of pyrazinamide-containing regimen for the initial treatment of pulmonary tuberculosis. The dose of pyrazinamide was 1.2 g per day irrespective of body weight. The patients of this treatment group consisted of 151 males and 39 females, and mean age of the males was 45.3 and that of the females was 43.8 years old. At the start of the treatment, 74% of the cases were smear positive, 70% were cavitary, and 6 cases each showed primary resistance to isoniazid and to streptomycin, respectively, and only one case showed resistance to both of isoniazid and streptomycin. There was no primary resistant case to either rifampicin or ethambutol. Bacteriologic negative conversion rates were 95% and 90% after 2 months of treatment by PZA-containing regimen and by the standard regimen, respectively, and treatment durations required to achieve the negative conversion of all cases were 3 and 6 months for respective regimens. Of 90 patients who completed 6-month PZA-containing regimen and could be followed-up, only one bacteriologic relapse (1.1%) was noticed. Elevation of serum GPT level higher than 150 IU/ml during the treatment was noticed in 6.3% of 175 cases under PZA-containing regimen in comparison with 4.0% of 174 cases under the standard regimen (not significant). The interval between the onset of the treatment and the detection of abnormal liver function was much shorter (mean 31.3 days) in the PZA-containing regimen than in the standard regimens (mean 63.4 days). Hyperuricaemia (> 10 mg/ml) was noticed in 46.7% of 57 males and 59.4% of 19 females tested, but pyrazinamide was not discontinued in any case due to arthralgia. These results clearly show that pyrazinamide can be used rather safely for Japanese tuberculosis patients. If the pyrazinamide-containing regimen [2HRS(E)Z/4HRE] is adopted as the new standard regimen in place of on-going standard regimen in Japan, 6HRS(E)/3HR, the duration of chemotherapy could be shortened by three months with the same level of both efficacy and safety. We recommended pyrazinamide-containing 6-month regimen, 2HRS(E)Z/4HRE, as the new standard regimen for the initial treatment of pulmonary tuberculosis.

摘要

1991年1月至1992年12月,419例肺结核患者在福寿寺医院接受初始治疗。其中,190例年龄小于80岁,患有有空洞或2级或3级播散性浸润的肺结核,和/或痰涂片阳性,采用含吡嗪酰胺的6个月短程方案2HRS(E)Z/4HRE进行治疗。这些患者符合评估含吡嗪酰胺方案对肺结核初始治疗的临床有效性的条件。吡嗪酰胺剂量不论体重均为每日1.2g。该治疗组患者包括151例男性和39例女性,男性平均年龄为45.3岁,女性平均年龄为43.8岁。治疗开始时,74%的病例痰涂片阳性,70%有空洞,分别有6例对异烟肼和链霉素原发耐药,仅1例对异烟肼和链霉素均耐药。对利福平或乙胺丁醇均无原发耐药病例。含PZA方案和标准方案治疗2个月后的细菌学阴转率分别为95%和90%,各方案实现所有病例阴转所需的治疗疗程分别为3个月和6个月。在完成含PZA的6个月方案且可进行随访的90例患者中,仅发现1例细菌学复发(1.1%)。含PZA方案治疗的175例患者中有6.3%在治疗期间血清GPT水平升高超过150IU/ml,而标准方案治疗的174例患者中这一比例为4.0%(无显著性差异)。含PZA方案治疗开始至肝功能异常检测的间隔时间(平均31.3天)比标准方案(平均63.4天)短得多。在接受检测的57例男性中有46.7%、19例女性中有59.4%出现高尿酸血症(>10mg/ml),但无一例因关节痛停用吡嗪酰胺。这些结果清楚表明,吡嗪酰胺对日本肺结核患者使用相当安全。如果在日本采用含吡嗪酰胺的方案[2HRS(E)Z/4HRE]作为新的标准方案取代现行标准方案6HRS(E)/3HR,化疗疗程可缩短3个月,而疗效和安全性相当。我们推荐含吡嗪酰胺的6个月方案2HRS(E)Z/4HRE作为肺结核初始治疗的新标准方案。

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