title: Development of ceftriaxone resistance in Salmonella enterica serotype Oranienburg during therapy for bacteremia.
abstract: BACKGROUND
  The majority of nontyphoid Salmonella infection is identified in children. When an invasive or severe Salmonella infection is encountered, ceftriaxone is recommended for such patients. A 2-year-old girl was hospitalized for the treatment of Salmonella bacteremia and discharged with standard ceftriaxone treatment. She was readmitted to the hospital after 2 days due to the recurrence of the Salmonella bacteremia. The study aimed to unveil the mechanism for the relapse.
  
  
  METHODS
  Six isolates (4 blood and 2 stool) were recovered from the patient, with the last two blood isolates being ceftriaxone-resistant. Pulsed-field gel electrophoresis was used for genotyping. Ceftriaxone resistance genes and transferability of the resistance plasmid were examined by molecular methods.
  
  
  RESULTS
  All isolates were identified as Salmonella enterica serotype Oranienburg. Five isolates demonstrated almost identical electrophoresis patterns, except that in the two ceftriaxone-resistant isolates an extra band (>100 kb) was noted. A blaCMY-2 gene, carried by a 120-kb conjugative IncI1 plasmid of the sequence type 53, was identified in the two ceftriaxone-resistant isolates. Transfer of the resistance plasmid from one blood isolate to Escherichia coli J53 resulted in the increase of ceftriaxone minimum inhibitory concentration from 0.125 μg/mL to 32 μg/mL in the recipient.
  
  
  CONCLUSIONS
  Ceftriaxone is the standard therapeutic choice for invasive or serious Salmonella infections in children. Pediatricians should be aware of the possibility of resistance development during therapy, especially in areas with a widespread of ceftriaxone resistance genes that are carried by a self-transferrable plasmid, such as the blaCMY-2-carrying IncI1 plasmid identified herein.
authors.affiliation: Division of Pediatric Gastroenterology, Department of Pediatrics, Chang Gung Children's Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Wei-Chiun
authors.initials: WC
authors.lastname: Yang
authors.affiliation: Division of Pediatric Gastroenterology, Department of Pediatrics, Chang Gung Children's Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Oi-Wa
authors.initials: OW
authors.lastname: Chan
authors.affiliation: Department of Laboratory Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Tsu-Lan
authors.initials: TL
authors.lastname: Wu
authors.affiliation: Molecular Infectious Disease Research Centre, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Chyi-Liang
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan; Molecular Infectious Disease Research Centre, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Medical Biotechnology and Laboratory Science, Chang Gung University College of Medicine, Taoyuan, Taiwan. Electronic address: sulinhui@gmail.com.
authors.forename: Lin-Hui
authors.initials: LH
authors.lastname: Su
authors.affiliation: Molecular Infectious Disease Research Centre, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Children's Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan. Electronic address: chchiu@adm.cgmh.org.tw.
authors.forename: Cheng-Hsun
authors.initials: CH
authors.lastname: Chiu
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D002443:Ceftriaxone / Q000627:therapeutic use*; D024881:Drug Resistance, Bacterial; D016521:Electrophoresis, Gel, Pulsed-Field; D005260:Female; D022761:Gene Transfer, Horizontal; D006801:Humans; D008826:Microbial Sensitivity Tests; D058889:Molecular Typing; D012008:Recurrence; D012480:Salmonella Infections / Q000188:drug therapy* / Q000382:microbiology; D019779:Salmonella enterica / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D017211:Treatment Failure
chemical_list: D000900:Anti-Bacterial Agents; D002443:Ceftriaxone
keywords: Ceftriaxone resistance; IncI1 plasmid; Relapse bacteremia; Salmonella enterica serotype Oranienburg