Nosocomial dissemination of hypervirulent Klebsiella pneumoniae with high-risk clones among children in Shanghai

Qingqing Du; Fen Pan; Chun Wang; Fangyuan Yu; Yingying Shi; Wenxin Liu; Zhi Li; Ping He; Dingding Han; Hong Zhang

doi:10.3389/fcimb.2022.984180

Nosocomial dissemination of hypervirulent Klebsiella pneumoniae with high-risk clones among children in Shanghai

Front Cell Infect Microbiol. 2022 Aug 29:12:984180. doi: 10.3389/fcimb.2022.984180. eCollection 2022.

Authors

Qingqing Du¹, Fen Pan¹, Chun Wang¹, Fangyuan Yu¹, Yingying Shi¹, Wenxin Liu¹, Zhi Li², Ping He³, Dingding Han¹, Hong Zhang¹

Affiliations

¹ Department of Clinical Laboratory, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
² Department of Pathology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
³ Department of Medical Microbiology and Immunology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Abstract

Objectives: Although hypervirulent Klebsiella pneumoniae (hvKp) is an increasing public health problem, there remains limited epidemiological information regarding hvKp infections in children. Here, we conducted a clinical, molecular and phenotypic surveillance of hvKp strains in a pediatric population.

Methods: Non-repetitive K. pneumoniae (Kp) strains consecutively collected during 2019-2020 were screened for hypervirulence genes (prmpA, prmpA2, iucA, iroB, and peg344) using PCR. Positive strains were further characterized by four phenotypic assays (string test, serum killing assay, siderophore production, Galleria mellonella lethality assay), followed by murine sepsis model to determine virulence in vitro and in vivo. Also, capsular types, sequence types, plasmid replicon types, antimicrobial resistance determinants and susceptibility were analyzed.

Results: A total of 352 isolates were collected, wherein 83 (23.6%) were hypervirulence genes-positive Kp (hgKp). A significant increase in KPC-2-producing KL47-ST11 among hgKp strains was observed, from 5.3% (1/19) in 2019 to 67.6% (25/37) in 2020 (P<.0001), suggesting the potential dissemination of the hybrid virulence and carbapenem-resistance encoding plasmid among children. Further, hgKp isolates were classified into hvKp (n = 27) and hgKp-low virulence (hgKp-Lv) (n = 56) based on virulence phenotypic assays. In hvKp, diverse genetic clones were observed and K1-ST23 or K2-ST25 strains with sensitivity to multiple antibiotics were prevalent (25.9%, 7/27). Compared with hgKp-Lv, hvKp infection had a higher propensity to involve severe pneumonia (22.2% vs. 12.5%) in elder children and significant higher mortality in mice (P = 0.0086). Additionally, either hvKp or hgKp-Lv infections were mostly healthcare-associated and hospital-acquired (74.1% vs. 91.9%).

Conclusions: These data suggest that K1-ST23 and K2-ST25 are high-risk clones of hvKp, and the genetic convergence of virulence and carbapenem-resistance is increasing among children. Control measures are needed to prevent the dissemination in clinical settings.

Keywords: Klebsiella pneumoniae; carbapenem-resistant; child; hypervirulence; infection; surveillance.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Bacterial Agents / pharmacology
Carbapenems
Child
China / epidemiology
Clone Cells
Cross Infection* / epidemiology
Hospitals
Humans
Klebsiella Infections* / epidemiology
Klebsiella pneumoniae
Mice

Substances

Anti-Bacterial Agents
Carbapenems