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

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.984180

DOI=10.3389/fcimb.2022.984180

ISSN=2235-2988

ABSTRACT=<sec><title>Objectives</title><p>Although hypervirulent <italic>Klebsiella pneumoniae</italic> (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.</p></sec><sec><title>Methods</title><p>Non-repetitive <italic>K. pneumoniae</italic> (Kp) strains consecutively collected during 2019-2020 were screened for hypervirulence genes (<italic>prmpA</italic>, <italic>prmpA2</italic>, <italic>iucA</italic>, <italic>iroB</italic>, and <italic>peg344</italic>) using PCR. Positive strains were further characterized by four phenotypic assays (string test, serum killing assay, siderophore production, <italic>Galleria mellonella</italic> lethality assay), followed by murine sepsis model to determine virulence <italic>in vitro</italic> and <italic>in vivo</italic>. Also, capsular types, sequence types, plasmid replicon types, antimicrobial resistance determinants and susceptibility were analyzed.</p></sec><sec><title>Results</title><p>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 (<italic>P</italic>&lt;.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 (<italic>P</italic> = 0.0086). Additionally, either hvKp or hgKp-Lv infections were mostly healthcare-associated and hospital-acquired (74.1% vs. 91.9%).</p></sec><sec><title>Conclusions</title><p>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.</p></sec>