title: Strain-specific transmission in an outbreak of ESBL-producing Enterobacteriaceae in the hemato-oncology care unit: a cohort study.
abstract: Extended-spectrum β-lactamase (ESBL)-producing bacteria are resistant to several types of antibiotics excluding carbapenems. A transmissibility of ESBL-producing Enterobacteriaceae would be depending on each bacterial property, however, that has not been elucidated in clinical setting. In this study, we attempted to identify the source of an outbreak of ESBL-producing bacteria in a medical oncology and immunology care unit.
  
  
  
  An ESBL-producing Enterobacteriaceae (ESBL-E) outbreak observed between July 2012 and August 2012 in Kagawa University Hospital was surveyed using various molecular microbiology techniques. We used Pulsed-field gel electrophoresis (PFGE), PCR-based ESBL gene typing, and direct sequence of ESBL gene as molecular microbiology typing method to distinguish each strain.
  
  
  
  The typical prevalence of ESBL-E isolation in the unit was 7.0 per month (1.7 per week). The prevalence of ESBL-E isolation during the target research period was 20.0 per month (5.0 per week). In total, 19 isolates (11 K. pneumoniae and 8 E. coli) were obtained from clinical samples, including four control strains (two each of both bacteria), that were physically different from those obtained from other inpatient units in our hospital. Pulsed-field gel electrophoresis (PFGE) for K. pneumoniae (digested by XbaI) produced similar patterns excluding one control strain. PCR classification of the ESBL gene for K. pneumoniae revealed that all strains other than the control strain carried SHV and CTX-M-9. This result was reconfirmed by direct DNA sequencing. Although the outbreak of K. pneumoniae was considered to be "clonal," PFGE and PCR classification of the ESBL genes for E. coli uncovered at least six different "non-clonal" strains possessing individual ESBL gene patterns. According to the result of an antibiogram, the pattern of antimicrobial susceptibility was more variable for K. pneumoniae than for E. coli.
  
  
  
  Typing by PFGE and ESBL gene PCR analysis is practical for discriminating various organisms. In our cohort, two outbreaks were concomitantly spread with different transmission strategies, namely clonal and non-clonal, in the same unit. This might represent clinical evidence that transmissibility differs according to the type of strain. We speculated that patient-to-patient transmission of ESBL-E occurred according to the properties of each individual strain.
authors.affiliation: Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Uemura
authors.affiliation: Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan. oima@med.kagawa-u.ac.jp.
authors.forename: Osamu
authors.identifier: 0000-0001-5332-1316
authors.initials: O
authors.lastname: Imataki
authors.affiliation: Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.
authors.forename: Shumpei
authors.initials: S
authors.lastname: Uchida
authors.affiliation: Division of Molecular Microbiology, Kagawa University, Kagawa, Japan.
authors.forename: Haruyuki
authors.initials: H
authors.lastname: Nakayama-Imaohji
authors.affiliation: Nursing Division, Kagawa University Hospital, Kagawa, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ohue
authors.affiliation: Nursing Division, Kagawa University Hospital, Kagawa, Japan.
authors.forename: Harumi
authors.initials: H
authors.lastname: Matsuka
authors.affiliation: Nursing Division, Kagawa University Hospital, Kagawa, Japan.
authors.forename: Hatsune
authors.initials: H
authors.lastname: Mori
authors.affiliation: Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Dobashi
authors.affiliation: Division of Molecular Microbiology, Kagawa University, Kagawa, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kuwahara
authors.affiliation: Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.
authors.forename: Norimitsu
authors.initials: N
authors.lastname: Kadowaki
mesh_terms: D000328:Adult; D000368:Aged; D015780:Carbapenems; D015331:Cohort Studies; D004196:Disease Outbreaks; D016521:Electrophoresis, Gel, Pulsed-Field; D004755:Enterobacteriaceae / Q000235:genetics* / Q000302:isolation & purification* / Q000472:pathogenicity; D004756:Enterobacteriaceae Infections / Q000453:epidemiology / Q000382:microbiology / Q000635:transmission*; D004926:Escherichia coli / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000453:epidemiology / Q000382:microbiology / Q000635:transmission; D005260:Female; D006757:Hospital Units; D006801:Humans; D007564:Japan / Q000453:epidemiology; D007710:Klebsiella Infections / Q000382:microbiology / Q000635:transmission; D007711:Klebsiella pneumoniae / Q000302:isolation & purification / Q000472:pathogenicity; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D058889:Molecular Typing; D016133:Polymerase Chain Reaction; D055815:Young Adult; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D015780:Carbapenems; D001618:beta-Lactamases
keywords: Escherichia coli; Extended-spectrum β-lactamase (ESBL); Klebsiella pneumoniae; Multidrug resistance; Non-clonal outbreak