Investigation of WQ-3810, a Fluoroquinolone with a High Potential Against Fluoroquinolone-Resistant Mycobacterium avium

<b>Background/Objectives:</b><i>Mycobacterium avium</i>, a member of <i>Mycobacterium avium</i> complex (MAC), is an emerging opportunistic pathogen causing MAC-pulmonary disease (PD). Fluoroquinolones (FQs), along with ethambutol (EMB) and rifampicin, are recommended for macrolide-resistant MAC-PD; however, FQ-resistant <i>M. avium</i> have been reported worldwide. WQ-3810 is an FQ with high potency against FQ-resistant pathogens; however, its activity against <i>M. avium</i> has not yet been studied. <b>Methods</b>: In this study, we conducted a DNA supercoiling inhibitory assay to evaluate the inhibitory effect of WQ-3810 on recombinant wild-type (WT) and four mutant DNA gyrases of <i>M. avium</i> and compared the IC₅₀s of WQ-3810 with those of ciprofloxacin (CIP), levofloxacin (LVX), and moxifloxacin (MXF). In addition, we examined WQ-3810's antimicrobial activity against 11 <i>M. avium</i> clinical isolates, including FQ-resistant isolates, with that of other FQs. Furthermore, we assessed the synergistic action of WQ-3810 with the combination of either EMB or isoniazid (INH). <b>Results</b>: In a DNA supercoiling inhibitory assay, WQ-3810 showed 1.8 to 13.7-fold higher efficacy than LVX and CIP. In the MIC assay, WQ-3810 showed 4 to 8-fold, 2 to 16-fold, and 2 to 4-fold higher antimicrobial activity against FQ-resistant isolates than CIP, LVX, and MXF, respectively. The combination of WQ-3810 and INH exhibited a synergistic relationship. <b>Conclusions</b>: The overall characteristics of WQ-3810 demonstrated greater effectiveness than three other FQs, suggesting that it is a promising option for treating FQ-resistant <i>M. avium</i> infections.