Nieto Ramirez Luisa Maria, Quintero Vargas Karina, Diaz Gustavo
Facultad de Ciencias Básicas, Universidad Santiago de Cali, Cali 760035, Colombia.
Facultad de Ciencias para la Salud, Departamento de Ciencias Básicas, Universidad de Caldas, Manizales 170002, Colombia.
Antibiotics (Basel). 2020 Mar 23;9(3):133. doi: 10.3390/antibiotics9030133.
Tuberculosis (TB) remains the deadliest Infectious disease worldwide, partially due to the increasing dissemination of multidrug and extensively drug-resistant (MDR/XDR) strains. Drug regimens containing the new anti-TB drugs bedaquiline (BDQ) and delamanid (DLM) appear as a last resort for the treatment of MDR or XDR-TB. Unfortunately, resistant cases to these drugs emerged just one year after their introduction in clinical practice. Early detection of resistant strains to BDQ and DLM is crucial to preserving the effectiveness of these drugs. Here, we present a systematic review aiming to define all available genotypic variants linked to different levels of resistance to BDQ and DLM that have been described through whole genomic sequencing (WGS) and the available drug susceptibility testing methods. During the review, we performed a thorough analysis of 18 articles. BDQ resistance was associated with genetic variants in and while mutations in were linked to a low-level of resistance for BDQ. For DLM, mutations in the genes , and were found in phenotypically resistant cases, while all the mutations in were reported only in DLM-susceptible strains. Additionally, WGS analysis allowed the detection of heteroresistance to both drugs. In conclusion, we present a comprehensive panel of gene mutations linked to different levels of drug resistance to BDQ and DLM.
结核病（TB）仍然是全球最致命的传染病，部分原因是耐多药和广泛耐药（MDR/XDR）菌株的传播日益增加。含有新型抗结核药物贝达喹啉（BDQ）和地拉米啶（DLM）的药物方案似乎是治疗MDR或XDR-TB的最后手段。不幸的是，这些药物在临床实践中应用仅一年后就出现了耐药病例。早期检测对BDQ和DLM的耐药菌株对于维持这些药物的有效性至关重要。在此，我们进行了一项系统综述，旨在确定通过全基因组测序（WGS）和可用的药物敏感性测试方法所描述的与对BDQ和DLM不同耐药水平相关的所有可用基因型变异。在综述过程中，我们对18篇文章进行了全面分析。BDQ耐药与[具体基因]的基因变异有关，而[具体基因]中的突变与BDQ的低水平耐药有关。对于DLM，在表型耐药病例中发现了[具体基因]、[具体基因]和[具体基因]中的突变，而[具体基因]中的所有突变仅在对DLM敏感的菌株中报道。此外，WGS分析能够检测到对这两种药物的异质性耐药。总之，我们提出了一组与对BDQ和DLM不同耐药水平相关的基因突变综合信息。
