title: Clinical and microbiologic characteristics of cefotaxime-non-susceptible Enterobacteriaceae bacteremia: a case control study.
abstract: Cefotaxime plays an important role in the treatment of patients with bacteremia due to Enterobacteriaceae, although cefotaxime resistance is reported to be increasing in association with extended-spectrum β-lactamase (ESBL) and AmpC β-lactamase (AmpC).
  
  
  
  We conducted a case-control study in a Japanese university hospital between 2011 and 2012. We assessed the risk factors and clinical outcomes of bacteremia due to cefotaxime-non-susceptible Enterobacteriaceae (CTXNS-En) and analyzed the resistance mechanisms.
  
  
  
  Of 316 patients with Enterobacteriaceae bacteremia, 37 patients with bacteremia caused by CTXNS-En were matched to 74 patients who had bacteremia caused by cefotaxime-susceptible Enterobacteriaceae (CTXS-En). The most common CTXNS-En was Escherichia coli (43%), followed by Enterobacter spp. (24%) and Klebsiella spp. (22%). Independent risk factors for CTXNS-En bacteremia included previous infection or colonization of CTXNS-En, cardiac disease, the presence of intravascular catheter and prior surgery within 30 days. Patients with CTXNS-En bacteremia were less likely to receive appropriate empirical therapy and to achieve a complete response at 72 h than patients with CTXS-En bacteremia. Mortality was comparable between CTXNS-En and CTXS-En patients (5 vs. 3%). CTXNS-En isolates exhibited multidrug resistance but remained highly susceptible to amikacin and meropenem. CTX-M-type ESBLs accounted for 76% of the β-lactamase genes responsible for CTXNS E. coli and Klebsiella spp. isolates, followed by plasmid-mediated AmpC (12%). Chromosomal AmpC was responsible for 89% of CTXNS Enterobacter spp. isolates.
  
  
  
  CTXNS-En isolates harboring ESBL and AmpC caused delays in appropriate therapy among bacteremic patients. Risk factors and antibiograms may improve the selection of appropriate therapy for CTXNS-En bacteremia. Prevalent mechanisms of resistance in CTXNS-En were ESBL and chromosomal AmpC.
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: Taro
authors.initials: T
authors.lastname: Noguchi
authors.affiliation: Department of Clinical Laboratory Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. yazblood@kuhp.kyoto-u.ac.jp.
authors.forename: Yasufumi
authors.identifier: 0000-0001-8595-8944
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: Masaki
authors.initials: M
authors.lastname: Yamamoto
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: 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: Shunji
authors.initials: S
authors.lastname: Takakura
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: Satoshi
authors.initials: S
authors.lastname: Ichiyama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D001426:Bacterial Proteins / Q000235:genetics; D016022:Case-Control Studies; D002439:Cefotaxime / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010957:Plasmids; D016896:Treatment Outcome; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; C048795:AmpC beta-lactamases; D001618:beta-Lactamases; D002439:Cefotaxime
keywords: Bacteremia; Cefotaxime-non-susceptible; Enterobacteriaceae