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

Area of Science:

• Microbiology
• Clinical Diagnostics
• Pharmaceutical Sciences

Background:

• Accurate drug susceptibility testing (DST) is crucial for treating tuberculosis (TB), especially multidrug-resistant TB (MDR-TB).
• Establishing reliable quality control (QC) ranges for Minimum Inhibitory Concentration (MIC) testing is essential for validating DST results.
• Existing QC ranges may not cover all essential antimycobacterials, including newer agents for MDR-TB.

Purpose of the Study:

• To establish reference MIC quality control (QC) ranges for a broad spectrum of antimycobacterial drugs.
• To validate the 7H9 broth microdilution MIC method for DST of first-line, second-line injectable, fluoroquinolone, and WHO category 5 drugs.
• To ensure the reliability and reproducibility of DST for Mycobacterium tuberculosis.

Main Methods:

• A tier-2 reproducibility study involving eight laboratories adhering to Clinical Laboratory and Standards Institute (CLSI) guidelines.
• Utilized custom-made 96-well microtiter plates with drugs diluted in 7H9 broth.
• Tested the Mycobacterium tuberculosis H37Rv reference strain to determine MIC frequency, mode, and geometric mean.

Main Results:

• Established QC ranges for 11 key antituberculosis drugs, including isoniazid, rifampin, ethambutol, levofloxacin, moxifloxacin, ofloxacin, amikacin, kanamycin, capreomycin, linezolid, and clofazimine.
• Data from one laboratory were excluded due to deviations from CLSI criteria, highlighting the importance of strict adherence.
• QC ranges could not be established for nicotinamide, prothionamide, or ethionamide due to assay nonperformance.

Conclusions:

• Reference MIC QC ranges were successfully established for most commonly used antituberculosis drugs against the M. tuberculosis H37Rv strain.
• The 7H9 broth microdilution MIC method, with the derived QC ranges, is suitable for reliable DST in resource-limited settings.
• These findings will improve the accuracy and consistency of drug susceptibility testing for TB management worldwide.