In vitro activity of flomoxef and comparators against Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis producing extended-spectrum β-lactamases in China

Qiwen Yang; Hui Zhang; Jingwei Cheng; Zhipeng Xu; Yingchun Xu; Bin Cao; Haishen Kong; Yuxing Ni; Yunsong Yu; Ziyong Sun; Bijie Hu; Wenxiang Huang; Yong Wang; Anhua Wu; Xianju Feng; Kang Liao; Dingxia Shen; Zhidong Hu; Yunzhuo Chu; Juan Lu; Jianrong Su; Bingdong Gui; Qiong Duan; Shufang Zhang; Haifeng Shao

doi:10.1016/j.ijantimicag.2014.11.012

In vitro activity of flomoxef and comparators against Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis producing extended-spectrum β-lactamases in China

Int J Antimicrob Agents. 2015 May;45(5):485-90. doi: 10.1016/j.ijantimicag.2014.11.012. Epub 2014 Dec 31.

Authors

Qiwen Yang¹, Hui Zhang¹, Jingwei Cheng¹, Zhipeng Xu¹, Yingchun Xu², Bin Cao³, Haishen Kong⁴, Yuxing Ni⁵, Yunsong Yu⁶, Ziyong Sun⁷, Bijie Hu⁸, Wenxiang Huang⁹, Yong Wang¹⁰, Anhua Wu¹¹, Xianju Feng¹², Kang Liao¹³, Dingxia Shen¹⁴, Zhidong Hu¹⁵, Yunzhuo Chu¹⁶, Juan Lu¹⁷, Jianrong Su¹⁸, Bingdong Gui¹⁹, Qiong Duan²⁰, Shufang Zhang²¹, Haifeng Shao²²

Affiliations

¹ 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.
² 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.
³ Chaoyang Hospital of Capital Medical College, Beijing 100020, China.
⁴ The First Affiliated Hospital of Zhejiang University, Hangzhou 310003, China.
⁵ Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China.
⁶ Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China.
⁷ Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
⁸ Zhongshan Hospital of Fu Dan University, Shanghai 200032, China.
⁹ The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
¹⁰ Shandong Provincial Hospital, Jinan 250021, China.
¹¹ Xiangya Hospital, Central Southern University, Changsha 410008, China.
¹² The First Affiliated Hospital of Zhengzhou University, Zhenzhou 450052, China.
¹³ The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
¹⁴ General Hospital of PLA, Beijing 100853, China.
¹⁵ General Hospital of Tianjin Medical University, Tianjing 300052, China.
¹⁶ The First Affiliated Hospital of Chinese Medical University, Shenyang 110001, China.
¹⁷ The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
¹⁸ Friendship Hospital of Capital Medical College, Beijing 100020, China.
¹⁹ The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
²⁰ People's Hospital of Jilin Province, Jilin 130021, China.
²¹ People's Hospital of Haikou City, Haikou 570208, China.
²² General Hospital of Nanjing Military Command, Nanjing 210002, China.

PMID: 25600890
DOI: 10.1016/j.ijantimicag.2014.11.012

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.

Keywords: Escherichia coli; Extended-spectrum β-lactamases; Flomoxef; Klebsiella pneumoniae; Proteus mirabilis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / pharmacology*
Cephalosporins / pharmacology*
China
Enterobacteriaceae Infections / microbiology
Escherichia coli / drug effects*
Escherichia coli / enzymology
Escherichia coli / isolation & purification
Hospitals
Humans
Klebsiella pneumoniae / drug effects*
Klebsiella pneumoniae / enzymology
Klebsiella pneumoniae / isolation & purification
Microbial Sensitivity Tests
Polymerase Chain Reaction
Proteus mirabilis / drug effects*
Proteus mirabilis / enzymology
Proteus mirabilis / isolation & purification
Sequence Analysis, DNA
beta-Lactamases / analysis
beta-Lactamases / genetics
beta-Lactamases / metabolism*

Substances

Anti-Bacterial Agents
Cephalosporins
beta-Lactamases
flomoxef