Investigation of the Rapid Emergence of Colistin Resistance in a Newborn Infected with KPC-2-Producing Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae

J Glob Antimicrob Resist. 2024 Sep:38:265-270. doi: 10.1016/j.jgar.2024.05.021. Epub 2024 Jun 6.

Abstract

Objectives: Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKp) poses a significant threat to public health. This study reports an infection related to hv-CRKp in a premature infant and reveals its colistin resistance and evolutionary mechanisms within the host.

Methods: Three KPC-producing CRKp strains were isolated from a patient with sepsis and CRKp osteoarthritis who had been receiving colistin antimicrobial therapy. The minimum inhibitory concentrations (MICs) of ceftazidime, ceftazidime-avibactam (CAZ-AVI), meropenem, imipenem, tigecycline, amikacin, minocycline, sulfamethoxazole/trimethoprim, ciprofloxacin, levofloxacin, aztreonam, cefepime, cefoperazone/sulbactam, piperacillin/tazobactam, and colistin were determined using the microbroth dilution method. The whole-genome sequencing analysis was conducted to determine the sequence types (STs), virulence genes, and antibiotic resistance genes of the three CRKp strains.

Results: Whole-genome sequencing revealed that all three CRKp strains belonged to the ST11 clone and carried a plasmid encoding blaKPC-2. The three strains all possessed the iucABCDiutA virulence cluster, peg-344 gene, and rmpA/rmpA2 genes, defining them as hv-CRKp. Further experiments and whole-genome analysis revealed that a strain of K. pneuomniae had developed resistance to colistin. The mechanism found to be responsible for colistin resistance was a deletion mutation of approximately 9000 bp including the mgrB gene.

Conclusion: This study characterizes colistin resistance of the ST11 clone hv-CRKp during colistin treatment and its rapid evolution within the host.

Keywords: Hypervirulent carbapenem-resistant Klebsiella pneumoniae; KPC-2; Whole-genome sequencing; Within-host evolution; mgrB.

Publication types

  • Case Reports

MeSH terms

  • Anti-Bacterial Agents* / pharmacology
  • Carbapenem-Resistant Enterobacteriaceae / drug effects
  • Carbapenem-Resistant Enterobacteriaceae / genetics
  • Carbapenem-Resistant Enterobacteriaceae / isolation & purification
  • Carbapenems / pharmacology
  • Colistin* / pharmacology
  • Drug Resistance, Bacterial / genetics
  • Drug Resistance, Multiple, Bacterial / genetics
  • Female
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Klebsiella Infections* / drug therapy
  • Klebsiella Infections* / microbiology
  • Klebsiella pneumoniae* / drug effects
  • Klebsiella pneumoniae* / genetics
  • Klebsiella pneumoniae* / isolation & purification
  • Klebsiella pneumoniae* / pathogenicity
  • Male
  • Microbial Sensitivity Tests*
  • Whole Genome Sequencing*
  • beta-Lactamases* / genetics

Substances

  • Colistin
  • beta-Lactamases
  • Anti-Bacterial Agents
  • Carbapenems