Genomic characterization of carbapenem-resistant organisms from pediatric patients with hematological malignancies and genomic comparison of infection versus intestinal colonizing strains
- 1Department of Clinical Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents' Health and Diseases, Hangzhou, Zhejiang, China
- 2Department of Hematology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents' Health and Diseases, Hangzhou, Zhejiang, China
Abstract
This study aimed to characterize the species distribution, sequence types, and antimicrobial resistance mechanisms of carbapenem-resistant organisms (CROs) in pediatric patients with hematological malignancies, and to clarify the genomic relationship between clinical infectious CROs and intestinal colonizing CROs. Non-duplicate infectious CRO strains and paired intestinal colonizing CROs were collected from 2020 to 2024. Whole-genome sequencing and bioinformatics analyses were performed to identify bacterial species, multilocus sequence types, resistance genes, mobile genetic elements, and genomic relatedness. Seven CRO species were identified, dominated by Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter hormaechei. A total of 34 carbapenem resistance-associated genes were detected, with efflux pump overexpression and antibiotic inactivation as the main mechanisms. Three patients carried both infectious and intestinal CROs. Two pairs showed nearly identical genomes (average nucleotide identity >99.99%), confirming infections originated from intestinal colonization. One pair belonged to different species but shared an identical KPC-2 gene located on the same Tn7247-like transposon, indicating potential horizontal gene transfer. Diverse CROs and corresponding resistance mechanisms are prevalent in pediatric patients with hematological malignancies. This study identifies the dominant CRO species and key resistance mechanisms in this high-risk population, supporting the gastrointestinal tract as a potential reservoir for CROs, and indicating the likelihood of horizontal transmission of carbapenemase genes. These findings underscore the necessity of intensive surveillance and strict infection control measures to curb the dissemination of CROs in vulnerable pediatric populations.IMPORTANCECarbapenem-resistant organisms (CROs) cause life-threatening infections in pediatric patients with hematological malignancies, who are highly vulnerable due to chemotherapy-induced immunosuppression. This study characterized CRO species, resistance mechanisms, and genomic links between infectious and intestinal colonizing strains in this population. We confirmed that intestinal colonization is an important source of subsequent CRO infections and identified interspecies horizontal transfer of the carbapenemase gene KPC-2 via a Tn7247-like transposon. These findings highlight the critical need for enhanced intestinal CRO screening and strict infection control measures to protect this vulnerable pediatric group.
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BibTeX
@article{fang2026genomic,
title = {{Genomic characterization of carbapenem-resistant organisms from pediatric patients with hematological malignancies and genomic comparison of infection versus intestinal colonizing strains}},
author = {Chao Fang and Zheng Zhou and Jianping Li and Xiucai Zhang and Jintao Xia and Shixing Liu and Yining Zhao and Xiaojun Xu and Shiqiang Shang and Mingming Zhou},
journal = {Microbiology Spectrum},
year = {2026},
month = oct,
doi = {10.1128/spectrum.01719-26},
url = {https://doi.org/10.1128/spectrum.01719-26},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Genomic characterization of carbapenem-resistant organisms from pediatric patients with hematological malignancies and genomic comparison of infection versus intestinal colonizing strains
AU - Chao Fang
AU - Zheng Zhou
AU - Jianping Li
AU - Xiucai Zhang
AU - Jintao Xia
AU - Shixing Liu
AU - Yining Zhao
AU - Xiaojun Xu
AU - Shiqiang Shang
AU - Mingming Zhou
PY - 2026
DA - 2026/10/02
JO - Microbiology Spectrum
DO - 10.1128/spectrum.01719-26
UR - https://doi.org/10.1128/spectrum.01719-26
AB - This study aimed to characterize the species distribution, sequence types, and antimicrobial resistance mechanisms of carbapenem-resistant organisms (CROs) in pediatric patients with hematological malignancies, and to clarify the genomic relationship between clinical infectious CROs and intestinal colonizing CROs. Non-duplicate infectious CRO strains and paired intestinal colonizing CROs were collected from 2020 to 2024. Whole-genome sequencing and bioinformatics analyses were performed to identify bacterial species, multilocus sequence types, resistance genes, mobile genetic elements, and genomic relatedness. Seven CRO species were identified, dominated by Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter hormaechei. A total of 34 carbapenem resistance-associated genes were detected, with efflux pump overexpression and antibiotic inactivation as the main mechanisms. Three patients carried both infectious and intestinal CROs. Two pairs showed nearly identical genomes (average nucleotide identity >99.99%), confirming infections originated from intestinal colonization. One pair belonged to different species but shared an identical KPC-2 gene located on the same Tn7247-like transposon, indicating potential horizontal gene transfer. Diverse CROs and corresponding resistance mechanisms are prevalent in pediatric patients with hematological malignancies. This study identifies the dominant CRO species and key resistance mechanisms in this high-risk population, supporting the gastrointestinal tract as a potential reservoir for CROs, and indicating the likelihood of horizontal transmission of carbapenemase genes. These findings underscore the necessity of intensive surveillance and strict infection control measures to curb the dissemination of CROs in vulnerable pediatric populations.IMPORTANCECarbapenem-resistant organisms (CROs) cause life-threatening infections in pediatric patients with hematological malignancies, who are highly vulnerable due to chemotherapy-induced immunosuppression. This study characterized CRO species, resistance mechanisms, and genomic links between infectious and intestinal colonizing strains in this population. We confirmed that intestinal colonization is an important source of subsequent CRO infections and identified interspecies horizontal transfer of the carbapenemase gene KPC-2 via a Tn7247-like transposon. These findings highlight the critical need for enhanced intestinal CRO screening and strict infection control measures to protect this vulnerable pediatric group.
SN - 2165-0497
ER -