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Klebsiella pneumoniae (KP) bloodstream infections (BSIs) are more common in immunocompromised patients and are associated with high rates of morbidity and mortality. Infants with an immature immune system and a lack of specific protective antibodies are susceptible to KP-BSIs. This study aimed to comprehensively investigate the clinical characteristics, antibiotic susceptibility profiles, treatment outcomes, and molecular characteristics of KP infections in these infants. Between January 2017 and December 2024, a retrospective study was conducted at Guangxi Children’s Hospital, China. We used logistic regression to identify risk factors for carbapenem-resistant KP BSI (CRKP-BSI) and extended-spectrum β-lactamase KP BSI (ESBL-KP-BSI), as well as mortality-associated factors in KP-BSI patients. Whole-genome sequencing (WGS) was conducted on CRKP isolates. Subsequent genomic analyses included multilocus sequence typing (MLST), capsular serotyping, virulence gene, and antimicrobial resistance gene through Pathogenwatch, complemented by plasmid replicon identification via PlasmidFinder. During the study period, 98 patients with KP-BSIs were enrolled. Of these patients, 16 were infected with CRKP and 82 with carbapenem-susceptible KP (CSKP). Among 82 CSKP cases, 29 had ESBL-KP and 53 had non-ESBL-KP. Multivariate analysis identified carbapenem exposure as an independent predictor of CRKP-BSIs (OR: 4.37, 95% CI: 1.12–16.98, p = 0.03), and β-lactam/β-lactamase inhibitor administration independently predicted ESBL-KP BSIs (OR: 3.59, 95% CI: 1.12–11.56, p = 0.03). The independent risk factors for the 30-day mortality in KP-BSIs was mechanical ventilation (OR: 4.71, 95% CI: 0.97–22.94, p = 0.05). MLST analysis identified four sequence types, with ST7 being the most prevalent, followed by ST24, ST20, and ST37. Capsular serotyping revealed KL54 as the predominant serotype. Antimicrobial resistance gene profiling indicated that all isolates harbored multiple resistance determinants, with blaNDM−1 and blaCTX−M−14 being universally present. The most prevalent replicons were IncX3, IncFII(K), IncR, and IncFIB(K), which frequently co-occurred. Furthermore, bioinformatic analysis indicated that these CRKP strains carried multiple resistance genes, with the likelihood that they are localized on plasmids. This study underscores the need for stricter antibiotic stewardship, especially in limiting exposure to carbapenems and β-lactam/β-lactamase inhibitors, as well as minimizing invasive procedures (e.g., mechanical ventilation) to reduce multidrug-resistant KP-BSI incidence and improve survival outcomes in infants.