Intestinal colonization of carbapenem-resistant gram-negative bacteria in pediatric hematology patients: risk factors and molecular characteristics, a multicenter case-control study

儿童血液病患者肠道内耐碳青霉烯类革兰氏阴性菌定植:危险因素和分子特征——一项多中心病例对照研究

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Abstract

OBJECTIVES: Aims to investigate the prevalence, risk factors, and molecular characteristics of intestinal colonized carbapenem-resistant gram-negative bacteria (CR-GNB) in pediatric hematology inpatients across China. METHODS: In this multicenter case control study, 412 pediatric inpatients with hematological diseases across China were screened for CR-GNB intestinal colonization. Antimicrobial susceptibility testing and whole-genome sequencing were performed on colonizing isolates. Logistic regression models were used to identify risk factors and construct a predictive nomogram. Comparative analyses between pediatric and adult patients were conducted to assess differences in colonization rates, resistance phenotypes, and resistance gene profiles. RESULTS: A total of 13.3% (55/412) of pediatric inpatients were colonized with CR-GNB, with carbapenem-resistant Enterobacterales (CRE) being the dominant group (10.0%, 41/412), followed by carbapenem-resistant Pseudomonas aeruginosa (CRPA) (3.2%, 13/412) and carbapenem-resistant Acinetobacter baumannii (CRAB) (0.2%, 1/412). Independent risk factors for colonization included younger age, acute leukemia, lymphoma, and hematopoietic stem cell transplantation (HSCT). Phylogenetic analyses showed no clonal dissemination and no regional clustering. NDM enzyme was prevalent in carbapenem-resistant E. coli (CREC) and Enterobacter spp., while CRKP isolates were mostly non-carbapenemase-producing, with resistance likely driven by extended-spectrum beta-lactamases (ESBLs) overexpression and porin loss. Compared with adults, pediatric CRE isolates exhibited significantly lower resistance to aminoglycosides and β-lactamase inhibitor combinations. CONCLUSIONS: This large-scale multicenter study highlights the substantial burden and molecular diversity of CR-GNB colonization in children with hematological diseases. Our findings underscore the need for pediatric-focused surveillance and infection control strategies that reflect species-specific resistance patterns and clinical vulnerabilities unique to this population. TRIAL REGISTRATION: ClinicalTrials.gov, registration number NCT05002582. (Registration date: 08 April 2021).

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