Goble M, Iseman M D, Madsen L A, Waite D, Ackerson L, Horsburgh C R
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
N Engl J Med. 1993 Feb 25;328(8):527-32. doi: 10.1056/NEJM199302253280802.
The frequency of infection with multidrug-resistant Mycobacterium tuberculosis is increasing. We reviewed the clinical courses of 171 patients with pulmonary disease due to M. tuberculosis resistant to rifampin and isoniazid who were referred to our hospital between 1973 and 1983. The patients' records were analyzed retrospectively. Their regimens were selected individually and preferably included three medications that they had not been given previously and to which the strain was fully susceptible.
The 171 patients (median age, 46 years) had previously received a median of six drugs and shed bacilli that were resistant to a median of six drugs. Thus, their regimens were frequently not optimal. Of 134 patients with sufficient follow-up data, 87 (65 percent) responded to chemotherapy (as indicated by negative sputum cultures for at least three consecutive months); 47 patients (35 percent) had no response, as shown by continually positive cultures. The median stay in the hospital was more than seven months. In a multivariate analysis, an unfavorable response was significantly associated with a greater number of drugs received before the current course of therapy (odds ratio, 4.0; 95 percent confidence interval, 1.6 to 9.9; P < 0.001) and with male sex (odds ratio, 2.5; 95 percent confidence interval, 1.1 to 6.2; P < 0.03). Twelve of the patients with responses subsequently had relapses. The overall response rate was 56 percent over a mean period of 51 months. Of the 171 patients, 63 (37 percent) died, and 37 of these deaths were attributed to tuberculosis.
For patients with pulmonary tuberculosis that is resistant to rifampin and isoniazid, even the best available treatment is often unsuccessful. Only about half of such patients eventually have negative sputum cultures despite carefully selected regimens administered for extended periods. Failure to control this resistant infection is associated with high mortality and ominous implications for the public health.
耐多药结核分枝杆菌感染的频率正在增加。我们回顾了1973年至1983年间转诊至我院的171例对利福平和异烟肼耐药的肺结核患者的临床病程。对患者的病历进行了回顾性分析。他们的治疗方案是个体化选择的，最好包括三种他们以前未使用过且该菌株对其完全敏感的药物。
171例患者（中位年龄46岁）此前平均接受过六种药物治疗，咳出的杆菌对六种药物耐药。因此，他们的治疗方案往往并不理想。在134例有充分随访数据的患者中，87例（65%）对化疗有反应（痰培养连续至少三个月呈阴性）；47例（35%）无反应，培养结果持续呈阳性。中位住院时间超过七个月。多因素分析显示，治疗反应不佳与当前疗程之前接受的药物数量较多（比值比4.0；95%置信区间1.6至9.9；P<0.001）以及男性性别（比值比2.5；95%置信区间1.1至6.2；P<0.03）显著相关。12例有反应的患者随后复发。在平均51个月的时间里，总体反应率为56%。171例患者中有63例（37%）死亡，其中37例死亡归因于结核病。
对于对利福平和异烟肼耐药的肺结核患者，即使是现有的最佳治疗方法也常常失败。尽管精心选择了治疗方案并长期给药，但这类患者中最终只有约一半的人痰培养呈阴性。无法控制这种耐药感染与高死亡率相关，并对公共卫生产生严重影响。
