Detection of Pyrazinamide Heteroresistance in Mycobacterium tuberculosis

Area of Science:

• Microbiology
• Infectious Diseases
• Genomics

Background:

• Heteroresistance, the presence of both susceptible and resistant bacteria, is observed in 9-57% of Mycobacterium tuberculosis isolates.
• Pyrazinamide (PZA) is a crucial first-line drug for TB treatment, with clinical resistance defined by >10% resistant bacteria.
• The diagnostic capacity of traditional methods for detecting PZA heteroresistance remains unevaluated.

Purpose of the Study:

• To compare Bactec MGIT 960, Wayne's test, and whole-genome sequencing (WGS) in detecting PZA-resistant subpopulations.
• To assess the ability of these methods to identify heteroresistance at critical thresholds.

Main Methods:

• Bacterial suspensions with varying proportions of PZA-resistant mutant strains were prepared.
• The performance of Bactec MGIT 960, Wayne's test, and WGS was evaluated for detecting PZA heteroresistance.

Main Results:

• Both Bactec MGIT 960 and WGS successfully detected the critical 10% level of PZA heteroresistance.
• Wayne's test failed to detect PZA heteroresistance, misclassifying resistant samples as susceptible.

Conclusions:

• Accurate detection of PZA heteroresistance is critical for effective TB treatment regimens.
• Bactec MGIT 960 and WGS show promise for diagnosing PZA heteroresistance, while Wayne's test is inadequate.
• Clinical awareness and evaluation of novel diagnostic tools for heteroresistance are essential for improving TB treatment outcomes.