Boudville I C, Wong S Y, Snodgrass I
Department of Clinical Epidemiology, Tan Tock Seng Hospital, Singapore.
Ann Acad Med Singap. 1997 Sep;26(5):549-56.
Singapore's tuberculosis incidence of 49 to 57 per 100,000 population for 1987 to 1996 presents a picture that is intermediate between developed and developing countries. The proportion of drug-resistant isolates has remained stable at 4.3% to 5.5% from 1992 to 1996 despite rising HIV rates. From 1995 to 1996, of the 199 consecutive drug-resistant isolates at the Central Tuberculosis Laboratory, 66% were mono-resistant, 22% dual-resistant and 12% resistant to more than two drugs. Isoniazid resistance was most prevalent, being found in 72% of isolates, followed by streptomycin resistance in 45%. Resistance to isoniazid and streptomycin (21%) was more common than to isoniazid and rifampicin, i.e. multidrug resistance (MDR) (14%). The small numbers indicated by the low overall prevalence of resistance and the predominance of single-drug resistance support the current initial choice of the standard short course with its three-drug initial phase. Of the 170 cases with matching National Tuberculosis Registry data, 72% of drug-resistant cases represented initial and 28% acquired resistance; testifying to the effectiveness of present day treatment regimens in suppressing resistance when compliance is assured. Case-control analysis using 244 drug-sensitive controls randomly selected from notifications in 1995 to 1996 showed an odds ratio for drug-resistance between subjects with a previous history and no previous history of tuberculosis of 2.47 (95% CI 1.40 to 4.37; P = 0.0007). With each increment in the number of episodes of tuberculosis experienced, there was a trend of resistance to progressively more drugs (P = 0.000004). This association remained even when a logistic regression model including all predictor variables was fitted. No associations were found with age, history of contact with tuberculosis, cavitary disease and, most notably, with human immunodeficiency virus infection. This study reaffirms that a history of previous tuberculosis should increase clinicians' index of suspicion for drug resistance, the urgency with which culture and sensitivity results are sought and the vigour with which patients are followed-up and compliance monitored.
1987年至1996年期间，新加坡的结核病发病率为每10万人中有49至57例，呈现出介于发达国家和发展中国家之间的情况。尽管艾滋病毒感染率上升，但从1992年至1996年，耐药菌株的比例一直稳定在4.3%至5.5%。1995年至1996年期间，在中央结核病实验室的199例连续耐药菌株中，66%为单耐药，22%为双耐药，12%对两种以上药物耐药。异烟肼耐药最为普遍，在72%的菌株中被发现，其次是链霉素耐药，占45%。对异烟肼和链霉素的耐药（21%）比对异烟肼和利福平的耐药，即多药耐药（MDR）（14%）更为常见。耐药总体患病率较低以及单药耐药占主导地位所显示的少量病例支持了目前标准短程疗法初始阶段采用三种药物的最初选择。在170例与国家结核病登记数据匹配的病例中，72%的耐药病例为初始耐药，28%为获得性耐药；这证明了当今治疗方案在确保依从性时抑制耐药的有效性。使用从1995年至1996年的通报中随机选择的244例药物敏感对照进行的病例对照分析显示，有结核病既往史和无结核病既往史的受试者之间耐药的优势比为2.47（95%可信区间1.40至4.37；P = 0.0007）。随着经历的结核病发作次数每增加一次，对更多药物产生耐药的趋势就越明显（P = 0.000004）。即使拟合了包含所有预测变量的逻辑回归模型，这种关联仍然存在。未发现与年龄、结核病接触史、空洞性疾病以及最显著的是与人类免疫缺陷病毒感染有关联。这项研究再次强调，结核病既往史应提高临床医生对耐药的怀疑指数、寻求培养和药敏结果的紧迫性以及对患者进行随访和监测依从性的力度。
