title: The Resistance Mechanism and Clonal Distribution of Tigecycline-Nonsusceptible Klebsiella pneumoniae Isolates in Korea.
abstract: OBJECTIVE
  Tigecycline is one of the drugs used to treat multi-drug resistant Klebsiella pneumoniae (K. pneumoniae) infections, including complicated skin and soft tissue infections, complicated intra-abdominal infection, and community-acquired pneumonia in the Republic of Korea. However, since its commercial release, K. pneumoniae resistance against tigecycline has been reported, and there is a serious concern about the spread of tigecycline resistant bacteria.
  
  
  METHODS
  In this study, we collected and analyzed 342 isolates from 23 hospitals in the Republic of Korea to determine the mechanisms of tigecycline susceptibility and their clonal types. The hospitals include several from each province in the Republic of Korea, except Jeju, an island province, and nonsusceptibility among the isolates was tested by the disk diffusion method. In our lab, susceptibility was checked again using the broth dilution method, and clonal types were determined using the multilocus sequence typing protocol. Real-time PCR was performed to measure the ramR mutation in the isolates nonsusceptible to tigecycline, which would suggest an increased expression of the AcrAB multidrug pump.
  
  
  RESULTS
  Fifty-six K. pneumoniae isolates were found to be nonsusceptible, 16% of the 342 collected. Twenty-seven and nine isolates of the tigecycline nonsusceptible isolates had mutations in the ramR and rpsJ genes, respectively; while 18 nonsusceptible isolates harbored the tetA gene. Comparison of isolates with and without ramR mutation showed a significant statistical difference (p<0.05) for expression of AcrAB. Moreover, the most common clonal types, as observed in our study, appear to be ST11 and ST789.
  
  
  CONCLUSIONS
  Several dominate clonal types infer tigecycline resistance to K. pneumoniae, including ST11, ST768, ST15, ST23, ST48, and ST307. There does not seem to be a transferrable medium, such as plasmid, for the resistance yet, although mutation of the ramR gene may be a common event, accounting for 48% of the nonsusceptibility in this study.
authors.affiliation: Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Korea.|Department of Environmental Medical Biology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Chulsoo
authors.initials: C
authors.lastname: Ahn
authors.affiliation: Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sang Sun
authors.initials: SS
authors.lastname: Yoon
authors.affiliation: Department of Environmental Medical Biology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Tae Soon
authors.initials: TS
authors.lastname: Yong
authors.affiliation: Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea.|Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Korea. KSCPJSH@yuhs.ac.
authors.forename: Seok Hoon
authors.initials: SH
authors.lastname: Jeong
authors.affiliation: Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea.|Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Kyungwon
authors.initials: K
authors.lastname: Lee
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001426:Bacterial Proteins; D024881:Drug Resistance, Bacterial; D006801:Humans; D007710:Klebsiella Infections / Q000188:drug therapy*; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification*; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D058885:Multilocus Sequence Typing; D010957:Plasmids; D016133:Polymerase Chain Reaction; D060888:Real-Time Polymerase Chain Reaction; D056910:Republic of Korea; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C095947:RamA protein, Klebsiella; D000078304:Tigecycline; D008911:Minocycline
keywords: Klebsiella pneumoniae; Tigecycline; ramR