Xiaofang Liang ¹ Zhihong Liu ¹ Yulin Wang ² Yu Zhang ¹ Wenbo Deng ¹ Qianqian Liu ³ Zhangping Lu ³ Keke Li ³ Yanbing Chang ³ Wei Lianhua ^3*

• ¹ School of Public Health, Gansu University of Chinese Medicine, Lanzhou, China
• ² School of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia Hui Region, China
• ³ Gansu Provincial Hospital, Lanzhou, Gansu Province, China

Antimicrobial resistance is among the greatest threats to public health globally, and drug repurposing strategies may be advantageous to addressing this problem. Mefloquine, a drug traditionally used to treat malaria, has emerged as a promising antibiotic adjuvant, due to its ability to enhance the effectiveness of conventional antibiotics against resistant bacterial strains. In this paper, we first outline the enhancement properties of mefloquine and its mechanisms of action as an adjuvant antibiotic against multidrug-resistant bacteria. Mefloquine exhibits synergistic bacteriostatic effects when combined with colistin, β-lactams, antituberculosis drugs, quinolones, and linezolid. Potential mechanisms underlying its synergistic effects include inhibition of antibiotic efflux, disruption of bacterial cell membrane integrity, and disturbance of biofilm formation. In addition, we explore the bacteriostatic effects of several mefloquine derivatives against Mycobacterium tuberculosis and some fungi. Further, we summarize the findings of recent studies on other aspects of mefloquine activity, including its antiviral and antitumor effects. Finally, the advantages and challenges of mefloquine use as an antibiotic adjuvant in combination with antibiotics for bacterial inhibition are discussed.Overall, mefloquine shows excellent potential as an antibiotic adjuvant therapy against multidrugresistant bacteria and is a promising candidate for combination therapy; however, further studies are needed to fully elucidate its mechanism of action and address the challenges associated with its clinical application.