Revisiting susceptibility testing in MDR-TB by a standardized quantitative phenotypic assessment in a European...

Area of Science:

• Microbiology
• Infectious Diseases
• Clinical Diagnostics

Background:

• Treatment outcomes for multidrug-resistant tuberculosis (MDR-TB) depend on appropriate second-line drug use guided by in vitro drug susceptibility testing (DST).
• Accurate and rapid DST is crucial for effective MDR-TB management.

Purpose of the Study:

• To establish a standardized, quantitative DST procedure for antituberculous drugs.
• To compare the results of this quantitative DST with genotypic resistance data.
• To evaluate the performance of the DST protocol across multiple European reference laboratories.

Main Methods:

• The study utilized the MGIT 960 system and TB eXiST software for automated DST.
• Resistance detection involved screening concentrations, followed by quantitative determination of resistance levels and proportions.
• Genotypic analysis investigated mutations in 14 gene regions associated with drug resistance.

Main Results:

• The study tested 139 Mycobacterium tuberculosis isolates against 13 antituberculous drugs.
• Phenotypic and genotypic resistance concordance exceeded 80%, with rapid results (median 10 days).
• High-level resistance was found in 49% of isolates, while 16% and 35% showed low and intermediate resistance, respectively.

Conclusions:

• The automated DST procedure enables accurate and rapid quantitative resistance profiling for first- and second-line antituberculous drugs.
• This method has the potential to guide personalized treatment regimens for MDR-TB.
• Further prospective validation is recommended to assess the impact on patient care.