Warren Robin M
SA MRC Centre for Tuberculosis Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, P.O. Box 241, Cape Town 8000, South Africa.
Int J Mycobacteriol. 2016 Dec;5 Suppl 1:S67. doi: 10.1016/j.ijmyco.2016.08.014. Epub 2016 Sep 21.
Contrary to classical dogma, molecular epidemiological studies and mathematical modeling clearly show that the global drug-resistant tuberculosis (TB) epidemic is driven by transmission. Furthermore, there is mounting evidence demonstrating that amplification of resistance occurs during treatment, possibly as a result of insufficient active drugs being administered. To control the drug-resistant TB epidemic, it will be essential to implement new, rapid, and highly sensitive and specific diagnostic methods to decrease the diagnostic delay associated with culture-based testing. To date, three molecular-based diagnostic tests have been endorsed by the World Health Organization: MTBDRplus (Hain Lifescience, Nehren, Germany) Xpert MTB/RIF (Cepheid, Sunnyvale, United States) MTBDRsl (Hain Lifescience, Nehren, Germany). Implementation of the MTBDRplus assay reduced the laboratory turnaround time from 55days to 27days. This was further reduced to 1day with the implementation of the Xpert MTB/RIF assay. However, time to initiation of multidrug-resistant TB (MDR-TB) treatment was not significantly reduced, remaining at approximately 17days from receipt of drug-susceptibility testing (DST) results. In an attempt to reduce the time to initiation of MDR-TB treatment, some guidelines have recommended initiating MDR-TB treatment based on the diagnosis of rifampicin resistance alone (within 5days). However, this implies treating MDR-TB blindly until routine culture-based DST results are available (mean, 54days). This strategy may be highly effective in countries where second-line treatment has only recently been introduced, but may have significant consequences for patients with resistance beyond MDR-TB sensu stricto. Implementation of the MTBDRsl assay promises to reduce the time for DST for fluoroquinolones and second-line injectable drugs. These tests will form the foundation for DST for the implementation of the recently recommended shortened MDR-TB regimen. The impact of the implementation of these tests on treatment outcome using either the standard or shortened MDR-TB remains to be determined.
与传统观念相反，分子流行病学研究和数学模型清楚地表明，全球耐药结核病疫情是由传播驱动的。此外，越来越多的证据表明，治疗期间耐药性会增强，这可能是由于所使用的活性药物不足所致。为了控制耐药结核病疫情，实施新的、快速且高度灵敏和特异的诊断方法以减少与基于培养的检测相关的诊断延迟至关重要。迄今为止，世界卫生组织已认可了三种基于分子的诊断检测方法：MTBDRplus（德国内伦海因生命科学公司）、Xpert MTB/RIF（美国森尼韦尔赛沛公司）、MTBDRsl（德国内伦海因生命科学公司）。MTBDRplus检测方法的实施将实验室周转时间从55天缩短至27天。随着Xpert MTB/RIF检测方法的实施，这一时间进一步缩短至1天。然而，耐多药结核病（MDR-TB）治疗开始时间并未显著缩短，从收到药敏试验（DST）结果起仍约为17天。为了缩短MDR-TB治疗开始时间，一些指南建议仅基于利福平耐药诊断（5天内）启动MDR-TB治疗。然而，这意味着在常规基于培养的DST结果出来之前（平均54天）盲目治疗MDR-TB。在二线治疗最近才引入的国家，这种策略可能非常有效，但对于严格意义上超出MDR-TB耐药范围的患者可能会产生重大后果。MTBDRsl检测方法的实施有望缩短氟喹诺酮类药物和二线注射用药物的DST时间。这些检测将为实施最近推荐的缩短的MDR-TB治疗方案的DST奠定基础。这些检测方法的实施对使用标准或缩短的MDR-TB治疗方案的治疗结果的影响仍有待确定。
