Stepwise decrease in moxifloxacin susceptibility amongst clinical isolates of multidrug-resistant Mycobacterium...

Area of Science:

• Microbiology
• Pharmacology
• Infectious Diseases

Background:

• Multidrug-resistant tuberculosis (MDR-TB) poses a significant global health challenge.
• Fluoroquinolones, including ofloxacin (OFX) and moxifloxacin (MOX), are vital in MDR-TB treatment regimens.
• Understanding drug susceptibility patterns is critical for effective therapeutic strategies.

Purpose of the Study:

• To evaluate the in vitro efficacy of moxifloxacin (MOX) against multidrug-resistant Mycobacterium tuberculosis (MDR-MTB) isolates.
• To compare MOX susceptibility with ofloxacin (OFX) susceptibility in MDR-MTB strains.
• To investigate the correlation between gyrase A mutations and MOX/OFX resistance.

Main Methods:

• In vitro drug susceptibility testing using the MGIT system for MOX and OFX.
• Analysis of 132 nonduplicate MDR-MTB isolates, including OFX-sensitive and OFX-resistant strains.
• DNA sequence analysis of gyrase A to identify resistance mutations.

Main Results:

• All OFX-susceptible strains were also susceptible to MOX.
• OFX-resistant isolates showed a 4- to 8-fold decrease in MIC for MOX compared to OFX.
• Gyrase A mutations, particularly Asp94Gly, correlated with decreased susceptibility to both OFX and MOX.

Conclusions:

• Moxifloxacin demonstrates significant in vitro activity against MDR-TB, including strains resistant to OFX.
• A breakpoint MIC of 2 mg/L for MOX in the MGIT system is suggested.
• Clinical use of MOX for MDR-TB requires vigilant monitoring of drug susceptibility due to potential stepwise resistance development.