Stepwise selection of mutation conferring fluroquinolone resistance: multisite MDR-TB cohort study

Area of Science:

• Microbiology
• Infectious Diseases
• Pharmacology

Background:

• Tuberculosis remains a significant global health threat.
• Multidrug-resistant tuberculosis (MDR-TB) poses treatment challenges.
• Fluoroquinolones (FQs) are crucial in MDR-TB treatment regimens.

Purpose of the Study:

• To investigate the risk of acquired fluoroquinolone resistance in Mycobacterium tuberculosis.
• To assess the impact of continuous FQ exposure on drug susceptibility.
• To evaluate the emergence of FQ resistance in patients undergoing MDR-TB treatment.

Main Methods:

• Analysis of Mycobacterium tuberculosis isolates from patients.
• Monitoring drug susceptibility to fluoroquinolones over time.
• Genomic analysis to identify resistance-associated mutations.

Main Results:

• Continuous fluoroquinolone exposure is associated with acquired drug resistance.
• Reduced susceptibility to FQs was observed in subsequent patient isolates.
• Stepwise selection of mutations correlated with increasing FQ resistance.

Conclusions:

• Urgent need for monitoring fluoroquinolone resistance in MDR-TB patients.
• Continuous FQ exposure can lead to treatment failure due to resistance.
• Strategies to mitigate acquired FQ resistance are essential for effective TB treatment.