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Abstract：
Patients with hematological diseases are considered to be at high risk for intestinal colonization by carbapenem-resistant Gram-negative bacteria (CR-GNB). However, the epidemiological data regarding risk factors and molecular characteristics of intestinal colonized CR-GNB isolates in this population are insufficient in China. A multicenter case‒control study involving 4,641 adult patients with hematological diseases from 92 hospitals across China was conducted. Following culture of collected rectal swabs, mass spectrometry and antimicrobial susceptibility tests were performed to identify GNB species and CR phenotype. Risk factors were assessed through retrospective clinical information. Whole-genome sequencing was used to analyze the molecular characteristics of CR-GNB isolates. This trial is registered with ClinicalTrials.gov as NCT05002582. Our results demonstrated that among 4,641 adult patients, 10.8% had intestinal colonization by CR-GNB. Of these, 8.1% were colonized by carbapenem-resistant Enterobacterales (CRE), 2.6% were colonized by carbapenem-resistant Pseudomonas aeruginosa (CRPA), and 0.3% were colonized by carbapenem-resistant Acinetobacter baumannii (CRAB). The risk factors for CR-GNB colonization include male gender, acute leukemia, hematopoietic stem cell transplantation, β-lactam antibiotic usage, and the presence of non-perianal infections within 1 week. Compared with CRPA-colonized patients, patients using carbapenems were more likely to be colonized with CRE. NDM was the predominant carbapenemase in colonized CRE. This study revealed a high CR-GNB intestinal colonization rate among adult patients with hematological diseases in China, with CRE being the predominant one. Notably, a significant proportion of CRE exhibited metallo-β-lactamase production, indicating a concerning trend. These findings emphasize the importance of active screening for CR-GNB colonization in patients with hematological diseases.IMPORTANCECarbapenem-resistant Gram-negative bacteria (CR-GNB) has emerged as a significant threat to public health. Patients with hematological diseases are at high risk of CR-GNB infections due to their immunosuppressed state. CR-GNB colonization is an independent risk factor for subsequent infection. Understanding the risk factors and molecular characteristics of CR-GNB associated with intestinal colonization in patients with hematological diseases is crucial for empirical treatment, particularly in patients with febrile neutropenia. However, the epidemiology data are still insufficient, and our study aims to determine the intestinal colonization rate of CR-GNB, identify colonization risk factors, and analyze the molecular characteristics of colonized CR-GNB isolates.
摘要：
患有血液病的患者被认为具有耐碳青霉烯的革兰氏阴性细菌（CR-GNB）的肠道定植的风险很高。然而,在中国，有关该人群中肠道定植的CR-GNB分离株的危险因素和分子特征的流行病学数据不足。进行了一项多中心病例对照研究，涉及来自中国92家医院的4,641名成人血液病患者。收集的直肠拭子培养后，进行了质谱和抗菌药物敏感性试验以鉴定GNB物种和CR表型。通过回顾性临床资料评估危险因素。全基因组测序用于分析CR-GNB分离株的分子特征。该试验在ClinicalTrials.gov注册为NCT05002582。我们的结果表明，在4,641名成年患者中，10.8％的人通过CR-GNB进行肠道定植。其中,8.1%被耐碳青霉烯类肠杆菌（CRE）定植，2.6%被耐碳青霉烯类铜绿假单胞菌(CRPA)定植,耐碳青霉烯鲍曼不动杆菌（CRAB）定植了0.3％。CR-GNB定植的危险因素包括男性,急性白血病,造血干细胞移植,β-内酰胺抗生素的使用，1周内出现非肛周感染。与CRPA定植患者相比，使用碳青霉烯类抗生素的患者更有可能被CRE定植.NDM是定植CRE中主要的碳青霉烯酶。这项研究揭示了在中国成人血液病患者中CR-GNB肠道定植率较高,CRE是主要的。值得注意的是,相当比例的CRE表现出金属β-内酰胺酶的产生，表明了一个令人担忧的趋势。这些发现强调了积极筛查血液疾病患者CR-GNB定植的重要性。耐IMPORTANCECarbapenem的革兰氏阴性菌（CR-GNB）已成为对公共卫生的重大威胁。血液病患者由于其免疫抑制状态而处于CR-GNB感染的高风险中。CR-GNB定植是后续感染的独立危险因素。了解CR-GNB与血液病患者肠道定植相关的危险因素和分子特征,对经验性治疗至关重要。特别是发热性中性粒细胞减少症患者。然而,流行病学数据仍然不足，我们的研究旨在确定CR-GNB的肠道定植率，确定定殖风险因素，并分析CR-GNB分离株的分子特征。
