https://orcid.org/0000-0003-0249-0755
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Abstract
Background
The rising prevalence of infections caused by carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKP) has outpaced our understanding of their evolutionary diversity. By straining the antimicrobial options and constant horizontal gene transfer of various pathogenic elements, CR-hvKP poses a global health threat.
Methods
Six KP isolates (KP1~KP6) from urine, sputum and groin infection secretion of a single patient were characterized phenotypically and genotypically. The antimicrobial susceptibility, carbapenemase production, hypermucoviscosity, serum resistance, virulence factors, MLST and serotypes were profiled. Genomic variations were identified by whole-genome sequencing and the phylogenetic differentiation was analyzed by Enterobacterial repetitive intergenic consensus (ERIC)-PCR.
Results
All KP strains were multi-drug resistant. Four of them (KP1, KP3, KP5 and KP6) belonged to ST11-K64, with high genetic closeness (relatedness coefficient above 0.96), sharing most resistance and virulence genes. Compared with KP1, the later isolates KP3, KP5 and KP6 acquired blaKPC-1 and lost blaSHV-182 genes. KP2 and KP4 had the same clonal origin of ST35-K16 (relatedness coefficient 0.98), containing almost identical genes for resistance and virulence. They were non-mucoid and carried blaNDM-5 gene.
Conclusion
A co-infection with two types of CR-hvKP affiliated with different clades within a single patient amplified the treatment difficulties. In addition to source control and epidemiological surveillance, investigation of the in-host interactions between CR-hvKP variants may provide valuable treatment solutions.
Abbreviations
KP, Klebsiella pneumoniae; ESBLs, extended-spectrum ß-lactamases; hvKP, hypervirulent KP; hmKP, hypermucoviscous KP; cKP, classical KP; CR-hvKP, carbapenem resistant hyper-virulent KP; KPC, Klebsiella pneumoniae carbapenemase; OXA-48, oxacillin-hydrolyzing β-lactamase; VIM, verona integron-encodes metallo-β-lactamase; IMP, imipenem-resistant phenotype; NDM, New Delhi metallo-β-lactamase; MLST, multi-locus sequence typing; ST, sequence type; ERIC (enterobacterial repetitive intergenic consensus); PCR, polymerase chain reaction; CFU, colony-forming units; WGS, whole-genome sequencing.
Ethics Approval and Patient Consent
The study was approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University. Since the patient is deceased, written informed consent for publication of his clinical details and clinical images was obtained from the next of kin. We confirm that informed consent obtained from all study participants prior to study commencement, and Guidelines outlined in the Declaration of Helsinki were followed.
Acknowledgment
The authors would like to thank Mr Dou-Dou Liu, a native English speaker, for helping us proofread the article.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas. HC and SL have contributed equally to the work, and are co-first authors. YF and HC conceived and designed the study. HC, SL and CZ collected the clinical specimen and performed the laboratory analyses. SL took part in drafting, and critically reviewing the article. HC and BL substantially reviewed the data analyses and revised the manuscript. All authors gave final approval of the version to be published. All authors have agreed on the journal to which the article has been submitted, and agree to be accountable for all aspects of the work.
Disclosure
The authors declare no potential conflict of interest.