Characteristics of antibiotic resistance and sequence type of Acinetobacter baumannii clinical isolates in Japan and the antibacterial activity of DS-8587.
DS-8587 is a novel broad-spectrum fluoroquinolone with extended antimicrobial activity against both Gram-positive and Gram-negative pathogens. In this study, we evaluated the antibacterial activity and mechanism of DS-8587 in 31 quinolone-resistant Acinetobacter baumannii clinical isolates. Efflux pump and qnr genes, mutations in quinolone resistance-determining regions of target enzymes, and sequence types determined by multilocus sequence typing were analyzed. Forty-two quinolone-susceptible clinical isolates were analyzed for comparison. For susceptibility testing, DS-8587 exhibited more effective antibacterial activity when compared with ciprofloxacin and levofloxacin. When combined with the efflux pump inhibitor 1-(1-napthylmethyl)-piperazine, the MIC of DS-8587 was less affected when compared with the MIC exhibited by combined ciprofloxacin and 1-(1-napthylmethyl)-piperazine. The efflux pump genes adeA/adeB/adeC and regulatory elements adeR/adeS were detected in 23 of 31 quinolone-resistant isolates. The qnrA/qnrB/qnrS genes were not detected in any A. baumannii isolates analyzed. Mutations in quinolone resistance-determining regions were observed in all 31 quinolone-resistant isolates. Multilocus sequence typing analyses revealed that 22 of 31 quinolone-resistant isolates belonged to ST-2, corresponding to international clonal lineage II. In conclusion, DS-8587 exhibits potent antibacterial activity against quinolone-resistant A. baumannii isolates that harbor mutations in quinolone resistance-determining regions. In the presence of the efflux pump inhibitor 1-(1-napthylmethyl)-piperazine, no significant changes were observed in the MIC for DS-8587. DS-8587 should be considered as a treatment option for A. baumannii including ST-2 strains that are predominant among the quinolone-resistant A. baumannii isolates found in Japan.
Biological Research Laboratories, Daiichi Sankyo, Co., Ltd., Tokyo, Japan; Department of Microbiology and Infection Control Science, Kyoto Pharmaceutical University, Yamashina, Kyoto, Japan. Electronic address: higuchi.saito.ir@daiichisankyo.co.jp.
Saito
S
Higuchi
Department of Microbiology and Infection Control Science, Kyoto Pharmaceutical University, Yamashina, Kyoto, Japan.
Mototsugu
M
Shikata
Biological Research Laboratories, Daiichi Sankyo, Co., Ltd., Tokyo, Japan.
Megumi
M
Chiba
Biological Research Laboratories, Daiichi Sankyo, Co., Ltd., Tokyo, Japan.
Kazuki
K
Hoshino
Department of Microbiology and Infection Control Science, Kyoto Pharmaceutical University, Yamashina, Kyoto, Japan.
Naomasa
N
Gotoh
D000151:Acinetobacter Infections / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D007564:Japan; D008826:Microbial Sensitivity Tests
D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; C000594795:DS-8587; D024841:Fluoroquinolones
Acinetobacter baumannii; Antibiotic resistance; Efflux pump; Quinolone resistance-determining regions; Quinolones