Comparison of the antibacterial activity of ofloxacin, levofloxacin, moxifloxacin, sitafloxacin, finafloxacin, and delafloxacin against strains isolated in China.

OBJECTIVE

The resistance of () to currently available fluoroquinolones (FQs), namely ofloxacin (OFX), levofloxacin (LFX), and moxifloxacin (MFX), renders the treatment of TB infections less successful. In this study, we aimed to evaluate the susceptibility and intracellular killing assay of to next-generation FQs and determine the correlation of FQs resistance and newly detected mutations in by molecular docking.

METHODS

Antimicrobial susceptibility test was performed to determine the minimum inhibitory concentrations (MICs) of six FQs, including currently available FQs (OFX, LFX, and MFX) and next-generation FQs, i.e., sitafloxacin (SFX), finafloxacin (FIN) and delafloxacin (DFX) against clinical isolates obtained in 2015 and 2022, respectively. Quinolone-resistance-determining regions of and were subjected to DNA sequencing and the correlation of FQs resistance and new mutations in were determined by molecular docking. Furthermore, the intracellular antibacterial activity of the six FQs against H37Rv in THP-1 cells was evaluated.

RESULTS

SFX exhibited the highest antibacterial activity against isolates (MIC = 0.25 μg/mL), whereas DFX and OFX exhibited comparable activity (MIC = 8 μg/mL). A statistically significant difference was observed among the MICs of the new generation FQs (SFX,  = 0.002; DFX,  = 0.008). Additionally, a marked increase in MICs was found in strains isolated in 2022 compared with those isolated in 2015. There might be correlation between FQs resistance and mutations in gyrB G520T and G520A. Cross-resistance rate between SFX and MFX was 40.6 % (26/64). At a concentration of 1 μg/mL, SFX exhibited high intracellular antibacterial activity (96.6 % ± 1.5 %) against the , comparable with that of MFX at a concentration of 2 μg/mL.

CONCLUSION

SFX exhibits the highest inhibitory activity against and THP-1 cell lines, which exhibits partial-cross resistance with MFX. There might be correlation between FQs resistance and mutations in G520T and G520A.Our findings provide crucial insights into the potential clinical application of SFX and DFX in the treatment of infections.