Worldwide, tuberculosis (TB) epidemic is characterized by a global decrease of incidence of antibiotic susceptible forms and an alarming onset of multidrug resistant (MDR) Mycobacterium tuberculosis strains, resistant to isoniazid and rifampicin. In these cases, and especially in cases of extensively drug resistant tuberculosis (XDR-TB), where the bacillus is also resistant to second-line antibiotics, fluoroquinolones and second-line injectables, there is an urgent need to stop the rise of resistance to the small therapeutic armamentarium available to fight tuberculosis. Nowadays, molecular tools are crucial to control and prevent tuberculosis and in particular of its resistant variants. Taking advantage of worldwide association genomic studies was possible to demonstrate the global evolution and dissemination of the different M. tuberculosis lineages, their association with latency, disease severity and ability to become drug resistant: old lineages are associated with latent tuberculosis and modern lineages are associated with active disease, fast transmission and drug resistance. Furthermore, the modern lineages are genetically better equipped to counteract the host response to the infection and become XDR through the acquisition of mutational resistance in antibiotic target genes associated with the overexpression of efflux pumps that overall, promote high-levels of resistance. The more we combat these strains with the standard diagnostic and therapeutic protocols, without knowing their genetic background and physiological response, the more they acquire resistance and limit patient clinical outcome. Drug-sensitive tuberculosis is easily curable...drug-resistant is much more complicated!!! The same evolutionary process of selection of resistance is now seen in nontuberculous mycobacteria (NTM), such as M. avium and M. abscessus that are becoming even more virulent, drug resistant and life threatening.
The inclusion of molecular tools in the mycobacteriological classic diagnosis algorithm allows early detection with clinical relevance, essential for a timely response and effective treatment of TB and NTM. Only through a complete interconnection between molecular laboratory data and clinical action can one avoid the development and transmission of resistant strains caused by inadequate therapeutic options.