Development of ceftriaxone resistance in Salmonella enterica serotype Oranienburg during therapy for bacteremia

J Microbiol Immunol Infect. 2016 Feb;49(1):41-5. doi: 10.1016/j.jmii.2014.01.011. Epub 2014 Mar 20.

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.

Conclusion: 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.

Keywords: Ceftriaxone resistance; IncI1 plasmid; Relapse bacteremia; Salmonella enterica serotype Oranienburg.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / therapeutic use*
  • Bacteremia / drug therapy*
  • Bacteremia / microbiology
  • Ceftriaxone / therapeutic use*
  • Drug Resistance, Bacterial*
  • Electrophoresis, Gel, Pulsed-Field
  • Female
  • Gene Transfer, Horizontal
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Typing
  • Recurrence
  • Salmonella Infections / drug therapy*
  • Salmonella Infections / microbiology
  • Salmonella enterica / classification
  • Salmonella enterica / drug effects*
  • Salmonella enterica / genetics
  • Salmonella enterica / isolation & purification
  • Treatment Failure

Substances

  • Anti-Bacterial Agents
  • Ceftriaxone