Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Koda-cho, Akitakata-shi, Hiroshima 739-1195, Japan.
Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Koda-cho, Akitakata-shi, Hiroshima 739-1195, Japan.
Int J Antimicrob Agents. 2014 Nov;44(5):443-9. doi: 10.1016/j.ijantimicag.2014.07.017. Epub 2014 Sep 1.
The aim of this study was to examine the in vitro antibacterial activity of WQ-3810, a new fluoroquinolone, against clinically relevant pathogens such as Acinetobacter baumannii, Escherichia coli and Streptococcus pneumoniae, including multidrug-resistant (MDR) and fluoroquinolone-resistant (FQR) isolates, compared with those of ciprofloxacin, levofloxacin, moxifloxacin and gemifloxacin. WQ-3810 demonstrated the most potent activity against the antimicrobial-resistant pathogens tested. Against A. baumannii, including MDR isolates, the potency of WQ-3810 [minimum inhibitory concentration for 90% of the organisms (MIC(90))=1 mg/L] was more than eight-fold higher than that of ciprofloxacin (64 mg/L) and levofloxacin (8 mg/L). Against E. coli and S. pneumoniae, including FQR isolates, WQ-3810 (MIC(90)=4 mg/L and 0.06 mg/L, respectively) was also more active than ciprofloxacin (64 mg/L and 2 mg/L) and levofloxacin (32 mg/L and 2 mg/L). Furthermore, WQ-3810 was the most potent among the fluoroquinolones tested against meticillin-resistant Staphylococcus aureus (MRSA) and Neisseria gonorrhoeae, including FQR isolates. In particular, WQ-3810 demonstrated highly potent activity against FQR isolates of A. baumannii, E. coli and S. pneumoniae with amino acid mutation(s) in the quinolone resistance-determining region of DNA gyrase and/or topoisomerase IV, which are the target enzymes of fluoroquinolones. An enzyme inhibition study performed using FQR E. coli DNA gyrase suggested that the potent antibacterial activity of WQ-3810 against drug-resistant isolates partly results from the strong inhibition of the target enzymes. In conclusion, this study demonstrated that WQ-3810 exhibits extremely potent antibacterial activity over the existing fluoroquinolones, particularly against MDR and FQR pathogens.
本研究旨在考察 WQ-3810（一种新型氟喹诺酮类药物）对临床相关病原体（如鲍曼不动杆菌、大肠埃希菌和肺炎链球菌，包括多重耐药（MDR）和氟喹诺酮耐药（FQR）分离株）的体外抗菌活性，并与环丙沙星、左氧氟沙星、莫西沙星和加替沙星进行比较。与环丙沙星和左氧氟沙星相比，WQ-3810 对检测到的抗微生物耐药病原体具有最强的活性。对包括 MDR 分离株在内的鲍曼不动杆菌，WQ-3810 的效力（MIC90 为 90%的目标物所需的最小抑制浓度）是环丙沙星（64mg/L）和左氧氟沙星（8mg/L）的 8 倍以上。对包括 FQR 分离株在内的大肠埃希菌和肺炎链球菌，与环丙沙星（64mg/L 和 2mg/L）和左氧氟沙星（32mg/L 和 2mg/L）相比，WQ-3810 也更具活性（MIC90 分别为 4mg/L 和 0.06mg/L）。此外，与测试的氟喹诺酮类药物相比，WQ-3810 对耐甲氧西林金黄色葡萄球菌（MRSA）和淋病奈瑟菌（包括 FQR 分离株）的活性最强。特别是，在 DNA 回旋酶和/或拓扑异构酶 IV 的喹诺酮耐药决定区有氨基酸突变的 FQR 鲍曼不动杆菌、大肠埃希菌和肺炎链球菌分离株中，WQ-3810 表现出高度的活性。用 FQR 大肠埃希菌 DNA 回旋酶进行的酶抑制研究表明，WQ-3810 对耐药分离株的强大抗菌活性部分归因于对靶酶的强烈抑制。总之，本研究表明，与现有氟喹诺酮类药物相比，WQ-3810 具有极强的抗菌活性，特别是对 MDR 和 FQR 病原体。
