Dual Transmission Dynamics of Carbapenem Resistance in Pediatric Oncology: Plasmid-Mediated and Clonal Spread of blaNDM-5 Enterobacterales.

INTRODUCTION: Carbapenem-resistant Enterobacterales (CRE) pose a major threat to immunocompromised pediatric oncology patients. However, the routes of resistance spread in this vulnerable population remain poorly understood, despite their importance for guiding infection control. METHODS: We analyzed 189 CRE bloodstream isolates (106 Escherichia coli, 72 Klebsiella pneumoniae, and 11 other Enterobacterales) collected at the Children's Cancer Hospital Egypt 57357 (August 2021-October 2022). Whole genome sequencing was used to assess sequence types, resistance genes, virulence factors, plasmid content, and transmission dynamics. RESULTS: Carbapenem resistance was primarily mediated by blaNDM-5, carried on species-specific plasmids: IncFIA/IncFII in E. coli and IncFIB/IncHIB megaplasmids in K. pneumoniae, frequently co-harboring additional aminoglycoside, sulfonamide, and fluoroquinolone resistance genes. The most common sequence types were ST361, ST167, and ST405 in E. coli, and ST11, ST383, and ST147 in K. pneumoniae. Clonal clustering was observed in 62.5% of K. pneumoniae but only 17% of E. coli. Plasmid phylogenetics and patient movement data indicated extensive horizontal plasmid transfer across unrelated lineages and patients, including ICU cases. A nonfunctional rmpA variant was found in 30 K. pneumoniae isolates, but no hypermucoviscous phenotype was observed. CONCLUSION: CRE bloodstream infections in pediatric oncology patients are driven by both clonal expansion and plasmid-mediated dissemination, with plasmids playing a dominant role, especially in E. coli. These findings highlight the limitations of strain-based surveillance and the need for integrated genomic and plasmid-level monitoring to inform infection control in high-risk hospital settings. A Graphical Abstract is available for this article.