title: Emergence of tigecycline- and carbapenem-nonsusceptible Klebsiella pneumoniae ST11 clone in patients without exposure to tigecycline.
abstract: OBJECTIVE
  Currently, tigecycline-nonsusceptible Klebsiella pneumoniae (TNSKP) is mainly reported to emerge following clinical use of tigecycline and is usually polyclonal. This study aimed to characterize TNSKP isolated from patients without prior tigecycline use.
  
  
  METHODS
  Twenty-six TNSKP clinical isolates were collected, and carbapenemase and 16S rRNA methylase genes were identified by polymerase chain reaction and sequencing. Molecular typing was conducted by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Clinical data of patients in the carbapenem-susceptible TNSKP group and the tigecycline- and carbapenem-nonsusceptible K. pneumoniae (TCNSKP) group were compared.
  
  
  RESULTS
  Of the 26 TNSKP isolates, eight contained both blaKPC-2and 16S rRNA methylase genes. In the remaining 18 TNSKP isolates, no carbapenemase gene was detected, and only three had the 16S rRNA methylase gene. Among the 26 isolates, 24 distinct pulsotypes and 19 sequence types (STs) were identified by PFGE and MLST, respectively. Six of the eight TCNSKP were ST11, whereas the remaining 18 TNSKP isolates were assigned to 17 different STs. No patient received tigecycline prior to the isolation of TNSKP. By comparison, intensive care unit exposure, mechanical ventilation, prior β-lactam/β-lactamase use, and longer hospitalization were more common for the TCNSKP group than for the carbapenem-susceptible TNSKP group.
  
  
  CONCLUSIONS
  TNSKP can occur without tigecycline use, and TCNSKP ST11 is predominant among them. Further, this report proposes potential risk factors for the occurrence of carbapenem-nonsusceptibility in TNSKP.
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China; Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Zi-Ke
authors.initials: ZK
authors.lastname: Sheng
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China; Institute of Biomedical Science, Fudan University, Shanghai, China.
authors.forename: Weixia
authors.initials: W
authors.lastname: Wang
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.
authors.forename: Qinglan
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Xu
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Wang
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China; Institute of Biomedical Science, Fudan University, Shanghai, China. Electronic address: mgwang@fudan.edu.cn.
authors.forename: Minggui
authors.initials: M
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000235:genetics*; D015780:Carbapenems / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D007710:Klebsiella Infections / Q000188:drug therapy* / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000302:isolation & purification; D008297:Male; D008780:Methyltransferases / Q000235:genetics; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008911:Minocycline / Q000031:analogs & derivatives* / Q000627:therapeutic use; D058885:Multilocus Sequence Typing; D016133:Polymerase Chain Reaction; D000078304:Tigecycline; D055815:Young Adult; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D000078304:Tigecycline; D008780:Methyltransferases; C035181:rRNA (adenosine-O-2'-)methyltransferase; D001618:beta-Lactamases; C547585:beta-lactamase KPC-2, Klebsiella pneumoniae; C063912:carbapenemase; D008911:Minocycline
keywords: Klebsiella pneumoniae; carbapenem resistance; risk factors; tigecycline resistance