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

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. 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 STs, virulence genes, and antibiotic resistance genes of three CRKp strains. Whole-genome sequencing revealed that all three CRKp strains belonged to the sequence type (ST) 11 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 Kp has developed resistance to colistin. The mechanism found to be responsible for the colistin resistance was a deletion mutation of approximately 9000 bp including mgrB gene. This study characterizes the colistin resistance of ST11 clone hv-CRKp during colistin treatment and its rapid evolution within the host.