title: In vitro activity of flomoxef and comparators against Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis producing extended-spectrum β-lactamases in China.
abstract: The objective of this study was to better understand the in vitro activity of flomoxef against clinical extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. A total of 401 ESBL-producing isolates, including 196 Escherichia coli, 124 Klebsiella pneumoniae and 81 Proteus mirabilis, were collected consecutively from 21 hospitals in China in 2013. Minimum inhibitory concentrations (MICs) were determined by broth microdilution methods. Phenotypic identification of ESBL production was detected as recommended by the Clinical and Laboratory Standards Institute (CLSI). ESBL genes were detected by PCR and sequencing. Flomoxef, doripenem, meropenem, ertapenem, cefmetazole and piperacillin/tazobactam exhibited good activity against ESBL-producing isolates, with susceptibility rates >90%. Tigecycline showed good activity against E. coli and K. pneumoniae (100% and 97.6%, respectively). Cefotaxime and cefepime showed very low activities against ESBL-producing isolates, with susceptibility rates of 0-0.8% and 1.0-13.6%, respectively. blaCTX-M were the major ESBL genes, with occurrence in 99.5% of E. coli, 91.1% of K. pneumoniae and 97.5% of P. mirabilis. blaCTX-M-14 was the predominant ESBL gene, detected in 46.9% (188/401) of the isolates, followed by blaCTX-M-15 (21.4%), blaCTX-M-55 (17.2%), blaCTX-M-65 (12.7%) and blaCTX-M-3 (6.7%). Flomoxef exhibited excellent activity against the different CTX-M-type ESBL-producing isolates, with MIC50 and MIC90 values of 0.064-0.125μg/mL and 0.25-0.5μg/mL, respectively. Against the isolates solely producing CTX-M-14, -15, -55, -3 or -65, flomoxef showed susceptibility rates of 98.6%, 98.0%, 98.1%, 100.0% and 97.4%, respectively. In conclusion, flomoxef showed good activity against ESBL-producing Enterobacteriaceae and may be a choice to treat infections caused by these isolates in China.
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, 1 Shuaifuyuan, Wangfujing Street, Beijing 100730, China.
authors.forename: Qiwen
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, 1 Shuaifuyuan, Wangfujing Street, Beijing 100730, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, 1 Shuaifuyuan, Wangfujing Street, Beijing 100730, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, 1 Shuaifuyuan, Wangfujing Street, Beijing 100730, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, 1 Shuaifuyuan, Wangfujing Street, Beijing 100730, China. Electronic address: xycpumch@139.com.
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Chaoyang Hospital of Capital Medical College, Beijing 100020, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Cao
authors.affiliation: The First Affiliated Hospital of Zhejiang University, Hangzhou 310003, China.
authors.forename: Haishen
authors.initials: H
authors.lastname: Kong
authors.affiliation: Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China.
authors.forename: Yuxing
authors.initials: Y
authors.lastname: Ni
authors.affiliation: Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China.
authors.forename: Yunsong
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Ziyong
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Zhongshan Hospital of Fu Dan University, Shanghai 200032, China.
authors.forename: Bijie
authors.initials: B
authors.lastname: Hu
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Huang
authors.affiliation: Shandong Provincial Hospital, Jinan 250021, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Xiangya Hospital, Central Southern University, Changsha 410008, China.
authors.forename: Anhua
authors.initials: A
authors.lastname: Wu
authors.affiliation: The First Affiliated Hospital of Zhengzhou University, Zhenzhou 450052, China.
authors.forename: Xianju
authors.initials: X
authors.lastname: Feng
authors.affiliation: The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Liao
authors.affiliation: General Hospital of PLA, Beijing 100853, China.
authors.forename: Dingxia
authors.initials: D
authors.lastname: Shen
authors.affiliation: General Hospital of Tianjin Medical University, Tianjing 300052, China.
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Hu
authors.affiliation: The First Affiliated Hospital of Chinese Medical University, Shenyang 110001, China.
authors.forename: Yunzhuo
authors.initials: Y
authors.lastname: Chu
authors.affiliation: The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Lu
authors.affiliation: Friendship Hospital of Capital Medical College, Beijing 100020, China.
authors.forename: Jianrong
authors.initials: J
authors.lastname: Su
authors.affiliation: The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Bingdong
authors.initials: B
authors.lastname: Gui
authors.affiliation: People's Hospital of Jilin Province, Jilin 130021, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Duan
authors.affiliation: People's Hospital of Haikou City, Haikou 570208, China.
authors.forename: Shufang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: General Hospital of Nanjing Military Command, Nanjing 210002, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Shao
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology*; D002681:China; D004756:Enterobacteriaceae Infections / Q000382:microbiology; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D006761:Hospitals; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D016133:Polymerase Chain Reaction; D011513:Proteus mirabilis / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D017422:Sequence Analysis, DNA; D001618:beta-Lactamases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D001618:beta-Lactamases; C045693:flomoxef
keywords: Escherichia coli; Extended-spectrum β-lactamases; Flomoxef; Klebsiella pneumoniae; Proteus mirabilis