A Multilaboratory, Multicountry Study To Determine Bedaquiline MIC Quality Control Ranges for Phenotypic Drug...

Area of Science:

• Microbiology
• Pharmacology
• Clinical Diagnostics

Background:

• Multidrug-resistant tuberculosis (MDR-TB) requires effective treatment options.
• Bedaquiline is a crucial antimycobacterial drug for treating MDR-TB.
• Standardized drug susceptibility testing (DST) is essential for accurate bedaquiline treatment guidance.

Purpose of the Study:

• To establish standardized DST methodologies for bedaquiline.
• To define reference Minimum Inhibitory Concentration (MIC) quality control (QC) ranges for bedaquiline.
• To ensure reliable and reproducible bedaquiline susceptibility testing in clinical laboratories.

Main Methods:

• Two tier-2 QC reproducibility studies were conducted across eight laboratories.
• Agar dilution and broth microdilution methods were evaluated following Clinical Laboratory and Standards Institute (CLSI) guidelines.
• Mycobacterium tuberculosis H37Rv served as the QC reference strain for MIC determination.

Main Results:

• Established QC range for agar dilution MIC: 0.015 to 0.12 μg/ml (95.8-95.9% concordance).
• Established QC range for broth microdilution MIC: 0.015 to 0.06 μg/ml (98.1% concordance).
• Demonstrated microbiological equivalence between 7H10 and 7H11 agar dilution methods.

Conclusions:

• Standardized bedaquiline DST methodologies and MIC QC ranges have been successfully established.
• These findings provide essential guidance for routine clinical bedaquiline DST globally.
• The established QC ranges and methods will be submitted to CLSI and EUCAST for broader adoption.