title: In vitro activity of WQ-3810, a novel fluoroquinolone, against multidrug-resistant and fluoroquinolone-resistant pathogens.
abstract: 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.
authors.affiliation: Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Koda-cho, Akitakata-shi, Hiroshima 739-1195, Japan. Electronic address: kazamori_d@wakunaga.co.jp.
authors.forename: Daichi
authors.initials: D
authors.lastname: Kazamori
authors.affiliation: Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Koda-cho, Akitakata-shi, Hiroshima 739-1195, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Aoi
authors.affiliation: Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Koda-cho, Akitakata-shi, Hiroshima 739-1195, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Sugimoto
authors.affiliation: Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Koda-cho, Akitakata-shi, Hiroshima 739-1195, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Ueshima
authors.affiliation: Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Koda-cho, Akitakata-shi, Hiroshima 739-1195, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Amano
authors.affiliation: Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Koda-cho, Akitakata-shi, Hiroshima 739-1195, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Itoh
authors.affiliation: Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Koda-cho, Akitakata-shi, Hiroshima 739-1195, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kuramoto
authors.affiliation: Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Koda-cho, Akitakata-shi, Hiroshima 739-1195, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yazaki
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D027081:DNA Gyrase / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D027081:DNA Gyrase
keywords: Antimicrobial resistance; Fluoroquinolones; WQ-3810