title: High prevalence of extended-spectrum β-lactamases and qnr determinants in Citrobacter species from Japan: dissemination of CTX-M-2.
abstract: OBJECTIVE
  Extended-spectrum β-lactamases (ESBLs) have become a problem among AmpC-producing Enterobacteriaceae and the emergence of concomitant quinolone resistance in β-lactamase-producing isolates poses a global threat. In this study we investigated the prevalence and regional variation of ESBLs in Japanese clinical isolates of Citrobacter spp. and analysed plasmid-mediated quinolone resistance (PMQR) determinants in ESBL-producing Citrobacter spp.
  
  
  METHODS
  A total of 348 clinical isolates of Citrobacter spp. collected throughout Japan were studied. Screening and the boronic acid disc test were performed to detect ESBLs in Citrobacter spp. with chromosomal AmpC β-lactamases. PCR and sequencing were done to identify ESBL and PMQR genes. For ESBL-producing Citrobacter spp., PFGE was performed using the SfiI restriction enzyme.
  
  
  RESULTS
  The number of ESBL-producing isolates confirmed phenotypically was 67 (19.3%). The prevalence of ESBL-producing Citrobacter koseri was significantly higher (32.1%) than that of ESBL-producing Citrobacter freundii (4.6%) (P < 0.01). Moreover, the prevalence of ESBLs was notably higher among C. koseri from southern Japan (60.0%). CTX-M-2 was predominant in C. koseri. Of the ESBL-producing C. koseri analysed, 23.2% possessed PMQR determinants, and there was a significant association between qnrB4 and bla(SHV-12). The 57 ESBL-producing Citrobacter spp. possessing bla(CTX-M), bla(SHV) or bla(TEM) were divided into 18 unique PFGE types.
  
  
  CONCLUSIONS
  This is the first report about the prevalence of PMQR determinants among ESBL-producing Citrobacter spp. from Japan. Our data suggest that ESBLs and PMQR determinants are spreading among C. koseri in Japan.
authors: Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan. kanamori@med.tohoku.ac.jp
authors: Hajime
authors: H
authors: Kanamori
authors: Hisakazu
authors: H
authors: Yano
authors: Yoichi
authors: Y
authors: Hirakata
authors: Shiro
authors: S
authors: Endo
authors: Kazuaki
authors: K
authors: Arai
authors: Miho
authors: M
authors: Ogawa
authors: Masahiro
authors: M
authors: Shimojima
authors: Tetsuji
authors: T
authors: Aoyagi
authors: Masumitsu
authors: M
authors: Hatta
authors: Mitsuhiro
authors: M
authors: Yamada
authors: Katsushi
authors: K
authors: Nishimaki
authors: Miho
authors: M
authors: Kitagawa
authors: Hiroyuki
authors: H
authors: Kunishima
authors: Mitsuo
authors: M
authors: Kaku
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D002954:Citrobacter / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics* / Q000302:isolation & purification; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004756:Enterobacteriaceae Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D006801:Humans; D007564:Japan; D008826:Microbial Sensitivity Tests; D015363:Quinolones / Q000494:pharmacology; D017422:Sequence Analysis, DNA; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015363:Quinolones; C071167:beta-lactamase CTX-2; C048795:AmpC beta-lactamases; D001618:beta-Lactamases