Drug susceptibility testing for Mycobacterium tuberculosis: a narrative review
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Tuberculosis (TB) remains a major global health threat, and the emergence and spread of drug-resistant Mycobacterium tuberculosis continue to undermine control efforts. Multidrug-resistant and rifampicin-resistant TB (MDR/RR-TB) is associated with prolonged treatment, higher toxicity, increased costs, and poorer outcomes compared to susceptible TB, making rapid and accurate drug susceptibility testing (DST) essential for effective patient management and transmission prevention. This review summarizes the current methods for DST in TB, focusing on the principles, strengths, and limitations of phenotypic and molecular approaches. Phenotypic DST, including the proportion, absolute concentration, and resistance ratio methods, and automated liquid culture systems, remains the conventional reference standard; however, conventional methods are limited by long turnaround times and technical complexity for certain drugs (such as pyrazinamide). Molecular DST targets resistance-associated mutations in key genes and is represented by line probe assays and cartridge-based platforms such as the Xpert MTB/RIF, which provide rapid results but are restricted to predefined genetic loci and may exhibit discordance with phenotypic DST, particularly with regard to borderline resistance. Next-generation sequencing (NGS)-based assays, including whole-genome sequencing and targeted NGS panels, offer comprehensive resistance profiling with high diagnostic accuracy and are increasingly being incorporated into international guidelines. Finally, we discuss the clinical interpretation of discordant results between genotypic and phenotypic DST, impact of revised rifampicin critical concentrations, and integration of DST results into contemporary World Health Organization guidelines and Korean treatment recommendations for MDR/RR-TB. Informed, methodologically grounded use of DST is crucial for optimizing the diagnosis and management of drug-resistant TB.
Abstract
Tuberculosis (TB) remains a major global health threat, and the emergence and spread of drug-resistant Mycobacterium tuberculosis continue to undermine control efforts. Multidrug-resistant and rifampicin-resistant TB (MDR/RR-TB) is associated with prolonged treatment, higher toxicity, increased costs, and poorer outcomes compared to susceptible TB, making rapid and accurate drug susceptibility testing (DST) essential for effective patient management and transmission prevention. This review summarizes the current methods for DST in TB, focusing on the principles, strengths, and limitations of phenotypic and molecular approaches. Phenotypic DST, including the proportion, absolute concentration, and resistance ratio methods, and automated liquid culture systems, remains the conventional reference standard; however, conventional methods are limited by long turnaround times and technical complexity for certain drugs (such as pyrazinamide). Molecular DST targets resistance-associated mutations in key genes and is represented by line probe assays and cartridge-based platforms such as the Xpert MTB/RIF, which provide rapid results but are restricted to predefined genetic loci and may exhibit discordance with phenotypic DST, particularly with regard to borderline resistance. Next-generation sequencing (NGS)-based assays, including whole-genome sequencing and targeted NGS panels, offer comprehensive resistance profiling with high diagnostic accuracy and are increasingly being incorporated into international guidelines. Finally, we discuss the clinical interpretation of discordant results between genotypic and phenotypic DST, impact of revised rifampicin critical concentrations, and integration of DST results into contemporary World Health Organization guidelines and Korean treatment recommendations for MDR/RR-TB. Informed, methodologically grounded use of DST is crucial for optimizing the diagnosis and management of drug-resistant TB.