title: Tigecycline resistance among carbapenem-resistant Klebsiella Pneumoniae: Clinical characteristics and expression levels of efflux pump genes.
abstract: OBJECTIVE
  Tigecycline is a treatment option for infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Emerging tigecycline resistance in CRKP represents a growing threat. Knowledge of the clinical, microbiological, and molecular characteristics of tigecycline- and carbapenem-resistant Klebsiella pneumoniae (TCRKP) is limited.
  
  
  METHODS
  Patients infected with TCRKP were identified from a Taiwanese national surveillance study. Clinical data were collected from medical records. We performed susceptibility tests, carbapenemase gene detection, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Furthermore, we performed quantitative real-time polymerase chain reaction (qRT-PCR) analyses to assess the expression levels of the efflux pump genes acrB and oqxB.
  
  
  RESULTS
  We identified 16 patients infected with TCRKP, with urinary tract infection (UTI) being the most common type of infection (63%). The all-cause 30-day mortality rate was 44% in patients with TCRKP infection. Patients with a site of infection other than the urinary tract had a significantly higher mortality rate than patients with UTIs (83% vs. 20%, p = 0.035). PFGE and MLST revealed no dominant clone or sequence type. Using qRT-PCR, overexpression of both the acrB and oqxB genes was identified in seven isolates, and overexpression of the oqxB gene was observed in another seven. There was poor correlation between acrB or oqxB expression and tigecycline MICs (r = -0.038 and -0.166, respectively).
  
  
  CONCLUSIONS
  The mortality rate in patients infected with TCRKP in this study was 44% and this is an important subset of patients. The absence of a linear relationship between efflux pump genes expression and MICs indicates that tigecycline resistance may be mediated by other factors. Continuous monitoring of tigecycline resistance among CRKP isolates and resistance mechanisms are necessary.
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.|Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Sheng-Kang
authors.initials: SK
authors.lastname: Chiu
authors.affiliation: Infection Control Office, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Ming-Chin
authors.initials: MC
authors.lastname: Chan
authors.affiliation: Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan, ROC.
authors.forename: Li-Yueh
authors.initials: LY
authors.lastname: Huang
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, National Yan-Ming University, Taipei, Taiwan, ROC.
authors.forename: Yi-Tsung
authors.initials: YT
authors.lastname: Lin
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Jung-Chung
authors.initials: JC
authors.lastname: Lin
authors.affiliation: Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC.
authors.forename: Po-Liang
authors.initials: PL
authors.lastname: Lu
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.|Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan, ROC.|Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, ROC.
authors.forename: L Kristopher
authors.initials: LK
authors.lastname: Siu
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Feng-Yee
authors.initials: FY
authors.lastname: Chang
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Kuo-Ming
authors.identifier: http://orcid.org/0000-0003-0446-7305
authors.initials: KM
authors.lastname: Yeh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001692:Biological Transport / Q000235:genetics; D015780:Carbapenems / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005260:Female; D005798:Genes, Bacterial; D006801:Humans; D007710:Klebsiella Infections / Q000188:drug therapy / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D060888:Real-Time Polymerase Chain Reaction; D000078304:Tigecycline; D014552:Urinary Tract Infections / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D000078304:Tigecycline; D008911:Minocycline