title: High prevalence of carbapenem resistance among plasmid-mediated AmpC β-lactamase-producing Klebsiella pneumoniae during outbreaks in liver transplantation units.
abstract: During a prospective surveillance using PCR for the detection of plasmid-mediated AmpC β-lactamase (pAmpC)-producing Enterobacteriaceae, outbreaks due to pAmpC-producing Klebsiella pneumoniae (pAmpC-Kp) occurred in an adult liver transplantation unit (aLTU) and a paediatric liver transplantation unit (pLTU), with carbapenem-resistant (CR) variants. Between April 2010 and March 2012, a total of 32 patients infected with pAmpC-Kp were found by prospective surveillance using PCR detection at a Japanese university hospital. Multilocus sequence typing, analysis of outer membrane proteins, and detection of carbapenemases were performed. Clinical courses of patients with bloodstream infection (BSI) were reviewed. Of 32 pAmpC-Kp isolates from each patient, 20 (18 from aLTU patients) were DHA-1-producing sequence type 11 (DHA-1-ST11), 9 were CMY-2-ST45/778 (all from pLTU patients) and the other 3 isolates had different sequence types. CR variants were isolated from 8 aLTU patients with DHA-1-ST11 and from 1 pLTU patient with CMY-2-ST45. All of the pAmpC-Kp isolates, including CR variants, were negative for carbapenemases. All of the DHA-1-ST11 and CMY-2-ST45 isolates lacked OmpK35, and seven CR variants also lacked OmpK36. BSIs due to DHA-1-ST11 isolates, including CR variants, occurred in six aLTU patients, four of whom died. The outbreaks were controlled after application of intensified infection control measures. During pAmpC-Kp outbreaks involving 27 liver transplants, CR variants with porin loss developed in nine patients, and DHA-1-ST11 K. pneumoniae caused BSIs with high mortality.
authors.affiliation: Department of Infection Control and Prevention, Kyoto University Hospital, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan; Department of Clinical Laboratory Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: yazblood@kuhp.kyoto-u.ac.jp.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Matsumura
authors.affiliation: Department of Clinical Laboratory Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Infection Control and Prevention, Kyoto University Hospital, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan; Department of Clinical Laboratory Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Infection Control and Prevention, Kyoto University Hospital, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan; Department of Clinical Laboratory Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Nagao
authors.affiliation: Department of Clinical Laboratory Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Kiyomasa
authors.initials: K
authors.lastname: Machida
authors.affiliation: Department of Clinical Laboratory Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan; Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Infection Control and Prevention, Kyoto University Hospital, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan; Department of Clinical Laboratory Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Takakura
authors.affiliation: Department of Hepato-pancreato-biliary, Transplant, and Pediatric Surgery, Kyoto University Hospital, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Ogawa
authors.affiliation: Department of Hepato-pancreato-biliary, Transplant, and Pediatric Surgery, Kyoto University Hospital, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yoshizawa
authors.affiliation: Department of Hepato-pancreato-biliary, Transplant, and Pediatric Surgery, Kyoto University Hospital, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujimoto
authors.affiliation: Department of Hepato-pancreato-biliary, Transplant, and Pediatric Surgery, Kyoto University Hospital, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Okamoto
authors.affiliation: Department of Hepato-pancreato-biliary, Transplant, and Pediatric Surgery, Kyoto University Hospital, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
authors.affiliation: Department of Infection Control and Prevention, Kyoto University Hospital, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan; Department of Clinical Laboratory Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ichiyama
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016470:Bacteremia / Q000453:epidemiology / Q000382:microbiology; D001426:Bacterial Proteins / Q000235:genetics*; D015780:Carbapenems / Q000494:pharmacology*; D016022:Case-Control Studies; D004269:DNA, Bacterial / Q000235:genetics; D004196:Disease Outbreaks; D005260:Female; D006785:Hospitals, University; D006801:Humans; D017053:Infection Control; D007564:Japan; D007710:Klebsiella Infections / Q000453:epidemiology* / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000302:isolation & purification; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D058885:Multilocus Sequence Typing; D010957:Plasmids; D016133:Polymerase Chain Reaction; D055815:Young Adult; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D004269:DNA, Bacterial; C048795:AmpC beta-lactamases; D001618:beta-Lactamases
keywords: AmpC; Carbapenems; Molecular epidemiology; Outer membrane protein