Increased Tuberculosis Patient Mortality Associated with Mycobacterium tuberculosis Mutations Conferring Resistance to Second-Line Antituberculous Drugs

摘要

Molecular diagnostics, with their ability to rapidly detect mutations in bacterial genes, have great potential to shorten the time between multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) (M/XDR-TB) diagnosis and appropriate treatment. These technologies identify mutations in the genome of Mycobacterium tuberculosis that confer phenotypic drug resistance, as defined by current phenotypic drug susceptibility testing (DST) at a single, “critical concentration” of the relevant drug compounds. However, recent studies have demonstrated that different M. tuberculosis mutations, even those occurring within the same gene region or codon, can confer different levels of phenotypic resistance to antituberculous drugs (as determined by quantitative DST, or by MIC testing, in solid or liquid media) (1–5). While studies correlating particular M. tuberculosis mutations with quantitative phenotypic resistance levels have helped clinicians to better understand the likely clinical relevance of molecular diagnostic assay results, it is still unclear whether specific mutations are directly associated with poor patient clinical outcomes.