title: Risk Factors, Outcomes, and Mechanisms of Tigecycline-Nonsusceptible Klebsiella pneumoniae Bacteremia.
abstract: A rise in tigecycline resistance in Klebsiella pneumoniae has been reported recently worldwide. We sought to identify risk factors, outcomes, and mechanisms for adult patients with tigecycline-nonsusceptible K. pneumoniae bacteremia in Taiwan. We conducted a matched case-control study (ratio of 1:1) in a medical center in Taiwan from January 2011 through June 2015. The cases were patients with tigecycline-nonsusceptible K. pneumoniae bacteremia, and the controls were patients with tigecycline-susceptible K. pneumoniae bacteremia. Logistic regression was performed to evaluate the potential risk factors for tigecycline-nonsusceptible K. pneumoniae bacteremia. Quantitative reverse transcription-PCR was performed to analyze acrA, oqxA, ramA, rarA, and kpgA expression among these isolates. A total of 43 cases were matched with 43 controls. The 14-day mortality of patients with tigecycline-nonsusceptible K. pneumoniae bacteremia was 30.2%, and the 28-day mortality was 41.9%. The attributable mortalities of tigecycline-nonsusceptible K. pneumoniae at 14 and 28 days were 9.3 and 18.6%, respectively. Fluoroquinolone use within 30 days prior to bacteremia was the only independent risk factor for tigecycline-nonsusceptible K. pneumoniae bacteremia. The tigecycline-nonsusceptible K. pneumoniae bacteremia was mostly caused by overexpression of AcrAB and/or OqxAB efflux pumps, together with the upregulation of RamA and/or RarA, respectively. One isolate demonstrated isolated overexpression of kpgA In conclusion, tigecycline-nonsusceptible K. pneumoniae bacteremia was associated with high mortality, and prior fluoroquinolone use was the independent risk factor for the acquisition of tigecycline-nonsusceptible K. pneumoniae The overexpression of AcrAB and/or OqxAB contributes to tigecycline nonsusceptibility in K. pneumoniae.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chih-Han
authors.initials: CH
authors.lastname: Juan
authors.affiliation: Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Huang
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan ytlin8@vghtpe.gov.tw.|Institute of Emergency and Critical Care Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yi-Tsung
authors.initials: YT
authors.lastname: Lin
authors.affiliation: Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Tsuey-Ching
authors.initials: TC
authors.lastname: Yang
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Fu-Der
authors.initials: FD
authors.lastname: Wang
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D016022:Case-Control Studies; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D007710:Klebsiella Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000235:genetics; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012307:Risk Factors; D013624:Taiwan; D000078304:Tigecycline; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D026901:Membrane Transport Proteins; D014157:Transcription Factors; D000078304:Tigecycline; D008911:Minocycline