Inserm Sorbonne universités, UPMC université Paris 06, CR7, U1135, centre d'immunologie et des maladies infectieuses, CIMI, Team E13 (bactériologie), 91, boulevard de l'hôpital, 75013 Paris, France; Centre national de référence des mycobactéries et de la résistance des mycobactéries aux antituberculeux (CNR-MyRMA), bactériologie-hygiène, hôpitaux universitaires Pitié-Salpêtrière-Charles-Foix, AP-HP, 47-83, boulevard de l'hôpital, 75013 Paris, France; Hôpitaux universitaires Saint-Louis-Lariboisière, AP-HP, 2, rue Ambroise-Paré, 75010 Paris, France.
Inserm Sorbonne universités, UPMC université Paris 06, CR7, U1135, centre d'immunologie et des maladies infectieuses, CIMI, Team E13 (bactériologie), 91, boulevard de l'hôpital, 75013 Paris, France; Centre national de référence des mycobactéries et de la résistance des mycobactéries aux antituberculeux (CNR-MyRMA), bactériologie-hygiène, hôpitaux universitaires Pitié-Salpêtrière-Charles-Foix, AP-HP, 47-83, boulevard de l'hôpital, 75013 Paris, France; Hôpitaux universitaires Saint-Louis-Lariboisière, AP-HP, 2, rue Ambroise-Paré, 75010 Paris, France.
Med Mal Infect. 2017 Sep;47(5):340-348. doi: 10.1016/j.medmal.2017.04.008. Epub 2017 Jun 17.
Molecular methods predict drug resistance several weeks before phenotypic methods and enable rapid implementation of appropriate therapeutic treatment. We aimed to detail the most representative molecular tools used in routine practice for the rapid detection of resistance to antituberculosis drugs among Mycobacterium tuberculosis strains.
The molecular diagnosis of resistance to antituberculosis drugs in clinical samples or from in vitro cultures is based on the detection of the most common mutations in the genes involved in the development of resistance in M. tuberculosis strains (encoding either protein targets of antibiotics, or antibiotic activating enzymes) by commercial molecular kits or by sequencing.
Three hypotheses could explain the discrepancies between the genotypic results and the phenotypic drug susceptibility testing results: a low percentage of resistant mutants precluding the detection by genotypic methods on the primary culture; a low level of resistance not detected by phenotypic testing; and other resistance mechanisms not yet characterized.
DISCUSSION/CONCLUSIONS: Molecular methods have varying sensitivity with regards to detecting antituberculosis drug resistance; that is why phenotypic susceptibility testing methods are mandatory for detecting antituberculosis drug-resistant isolates that have not been detected by molecular methods. The questionable ability of existing phenotypic and genotypic drug susceptibility testing to properly classify strains as susceptible or resistant, and at what level of resistance, was raised for several antituberculosis agents.
分子方法可在表型方法之前预测数周的耐药性，并能快速实施适当的治疗。我们旨在详细介绍在常规实践中用于快速检测结核分枝杆菌菌株对抗结核药物耐药性的最具代表性的分子工具。
临床样本或体外培养物中抗结核药物耐药性的分子诊断是基于通过商业分子试剂盒或测序检测结核分枝杆菌菌株中耐药性发展相关基因（编码抗生素的蛋白靶标或抗生素激活酶）中最常见的突变。
有三个假设可以解释基因型结果与表型药敏试验结果之间的差异：初级培养物中耐药突变体的比例低，无法通过基因方法检测；表型检测未检测到低水平的耐药性；以及尚未表征的其他耐药机制。
讨论/结论：分子方法在检测抗结核药物耐药性方面的灵敏度不同；这就是为什么表型药敏试验方法对于检测未被分子方法检测到的抗结核药物耐药分离株是强制性的。对于几种抗结核药物，现有的表型和基因型药敏试验方法是否有能力正确分类为敏感或耐药菌株，以及在何种耐药水平上，存在疑问。
