A nosocomial outbreak of colistin and carbapenem-resistant hypervirulent Klebsiella pneumoniae in a large teaching hospital

• Published in: Scientific reports 2024-11, Vol.14 (1), p.27744-12, Article 27744
• Main Authors: Jian, Zijuan, Liu, Yanjun, Wang, Zhiqian, Zeng, Lanman, Yan, Qun, Liu, Wenen
• Format: Article
• Language: English
• Subjects: 631/326; 692/4017; Aged; Amino acid sequence; Amino acids; Animal models; Animals; Anti-Bacterial Agents - pharmacology; Antibiotics; Antimicrobial agents; Antimicrobial resistance; Carbapenem-resistance; Carbapenems; Carbapenems - pharmacology; Colistin; Colistin - pharmacology; Colistin-resistance; Complementation; Cross Infection - epidemiology; Cross Infection - microbiology; Disease Outbreaks; Drug resistance; Drug Resistance, Multiple, Bacterial - genetics; Female; Genes; Hospitals; Hospitals, Teaching; Humanities and Social Sciences; Humans; Hypervirulent; Infection prevention and control; Insertion sequences; Klebsiella Infections - epidemiology; Klebsiella Infections - microbiology; Klebsiella pneumoniae; Klebsiella pneumoniae - drug effects; Klebsiella pneumoniae - genetics; Klebsiella pneumoniae - isolation & purification; Klebsiella pneumoniae - pathogenicity; Male; Mice; Microbial Sensitivity Tests; Middle Aged; multidisciplinary; Mutation; Nosocomial infection; Nosocomial infections; Nucleotide sequence; Outbreaks; Phenotypes; Phylogeny; PmrA gene; PmrB gene; Prevention; Science; Science (multidisciplinary); Virulence - genetics; Virulence factors; Virulence Factors - genetics; Whole Genome Sequencing
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-79030-w

Recently, colistin and carbapenem-resistant hypervirulent Klebsiella pneumoniae (CCR-hvKP) has been observed sporadically. The aim of this study was to report a nosocomial outbreak due to CCR-hvKP, so as to control the transmission of CCR-hvKP and prevent future outbreaks. The clinical characteristics of five involved cases were analyzed and infection prevention and control measures were documented. Five CCR-hvKP isolates were discovered from the five involved cases. Molecular features of the isolates including sequence type, capsule locus, antimicrobial resistance genes, virulence factors and phylogenetic relationship were analyzed by whole-genome sequencing. Validation of the role of the deleterious amino acid mutations to colistin resistance was examined by complementation assays. PCR was performed to identify insertion sequences within the mgrB gene. Mouse intraperitoneal infection models were used to assess virulence phenotype. Five cases infected with CCR-hvKP were identified with a high attributable mortality rate of 60% in the patients. The five outbreak isolates belonged to the high-risk ST11-KL64 clone and were closely clustered. They were highly resistant to commonly used antibiotics and showed hypervirulent in vivo. WGS revealed multiple antimicrobial resistance genes such as bla KPC-2 and bla CTX-M-65 and important virulence factors. Concerning colistin resistance, amino acid mutations G53S in pmrA gene, and T157P, T246A and R256G in pmrB gene were indentified. Among them, the deleterious mutation T157P in pmrB gene was validated to be responsible for the resistance phenotype of isolate KP01, KP03 and KP05. In addition, disruption of mgrB gene by insertion sequences of IS Kpn26 and IS 903B was indentified in isolate KP02 and KP04, respectively. This is the first report of an outbreak caused by CCR-hvKP. The study highlights infection prevention and control measures are key to successfully fight against CCR-hvKP dissemination and nosocomial infections. Continuous surveillance should be performed to limit the spread of these isolates.