Heifets L B, Cangelosi G A
National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Int J Tuberc Lung Dis. 1999 Jul;3(7):564-81.
The prevailing opinion in most of the world is that drug susceptibility testing of Mycobacterium tuberculosis isolates may not be necessary, especially in countries where the diagnosis of tuberculosis is based predominantly on sputum smear examination without culture isolation, and even if it were functionally important it is too expensive to be practical. However, we believe that the spread of primary drug resistance calls for immediate action to prevent the real threat in a number of countries of an epidemic of incurable polyresistant tuberculosis. One step in this direction, among other necessary measures, is implementation of a system for timely detection of drug resistance in new patients. An overview of the currently available methods for drug susceptibility testing, and those under development, is presented in this article. Our aim is to stimulate discussion regarding where, when, and which methods can and should be implemented now, and which of them has the best potential for the future. This overview includes phenotypic approaches based on conventional cultivation and other techniques, as well as perspectives for the genotypic principle. Regardless of the methods chosen for now or to be implemented in the future, they are all laboratory methods, and we contend that dreams of a revolutionary method which can do away with the laboratory are unrealistic, at least for the time being. We argue that it is essential to create a system of direct, centralized laboratory services in order to make drug susceptibility testing reliable, practical and affordable. Such centralized laboratories would provide both more timely and trustworthy diagnosis of tuberculosis, and facilitate detection of primary drug resistance. Although such systems would require significant initial investment, we suggest that, over time, they would prove highly cost-effective for many countries.
世界上大多数地方的普遍观点是,对结核分枝杆菌分离株进行药物敏感性测试可能没有必要,特别是在那些主要基于痰涂片检查而非培养分离来诊断结核病的国家,而且即使其功能上很重要,实施起来也过于昂贵而不切实际。然而,我们认为原发性耐药的传播需要立即采取行动,以防止在一些国家出现无法治愈的多重耐药结核病流行这一真正威胁。朝着这个方向迈出的一步,除其他必要措施外,是建立一个及时检测新患者耐药性的系统。本文概述了目前可用的药物敏感性测试方法以及正在研发的方法。我们的目的是激发关于现在可以且应该在何处、何时以及采用哪些方法实施检测,以及其中哪些方法在未来具有最佳潜力的讨论。这一概述包括基于传统培养和其他技术的表型方法,以及基因型原理的相关观点。无论现在选择或未来实施何种方法,它们都是实验室方法,而且我们认为,至少在目前,那种能够摒弃实验室的革命性方法的梦想是不现实的。我们认为,建立一个直接的、集中化的实验室服务体系至关重要,以便使药物敏感性测试可靠、实用且经济实惠。这样的集中化实验室将能更及时、更可靠地诊断结核病,并有助于检测原发性耐药。虽然这样的系统需要大量的初始投资,但我们认为,随着时间的推移,它们对许多国家来说将证明具有很高的成本效益。