Zhang Yan, Ni Shuangling, Hu Hangbin, Zhang Sheng, Feng Haiting, Ni Lingmei, Chen Hongchao, Yang Qing, Yu Meihong, Qu Tingting
State Key Laboratory for Diagnosis and Treatment of Infectious Disease, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, People's Republic of China.
Infectious Disease Department, Lishui People's Hospital, Lishui, 323000, People's Republic of China.
Infect Drug Resist. 2025 May 27;18:2687-2701. doi: 10.2147/IDR.S514373. eCollection 2025.
To describe the clinical and molecular characteristics of β-lactam/β-lactamase inhibitor combinations (BLBLIs) non-susceptible ESBL-producing Enterobacteriaceae (BnESBL-E) bloodstream infections (BSIs).
A cohort study was performed with ESBL-E-BSI cases from 2017 to 2019 in East China. Clinical characteristics, risk factors, and all-course mortality were evaluated. Whole-genome sequencing and antibiotic susceptibility testing were performed.
Among the 187 patients with ESBL-E-BSI, 39.57% (74/187) had BnESBL-E-BSI. Nosocomial infections constituted 63.51% of BnESBL-E-BSIs, and 39.19% of cases originated from intra-abdominal sources. Risk factors for BnESBL-E-BSI included BLBLIs exposure within the preceding 3 months, ICU admission within the last 3 months, and the duration of hospital stay prior to BSI. Notably, a urinary source of bacteremia emerged as a protective factor against BnESBL-E-BSI(OR, 0.177; 95% CI, 0.049-0.647; =0.009). BnESBL-E-BSIs were associated with a higher 28-day mortality compared to BLBLIs-susceptible cases (31.08%vs.16.81%; =0.031). Multivariate analysis identified the Pitt bacteremia score, CRP level, and hospitalization within the preceding 3 months as risk factors for BnESBL-E-BSI-related mortality, while receipt of carbapenems within 72 hours of symptom onset improved survival(OR, 0.128; 95% CI, 0.018-0.912; = 0.04). BnESBL-E isolates demonstrated no clonal transmission and remained highly susceptible to amikacin, carbapenems and tigecycline. Coexistence of multiple ESBL types was frequently observed, occurring in 40.6% of BnESBL- and 72.7% of BnESBL- isolates.
Given the high prevalence and mortality of BnESBL-E-BSI, carbapenems may be preferable treatment option for non-urinary ESBL-E-BSIs. BnESBL-E represents an underestimated clinical threat, warranting timely identification of risk factors and the consideration of appropriate empirical therapy.
描述对β-内酰胺/β-内酰胺酶抑制剂复方制剂（BLBLIs）不敏感的产超广谱β-内酰胺酶肠杆菌科细菌（BnESBL-E）血流感染（BSIs）的临床和分子特征。
对2017年至2019年华东地区的产ESBL-E血流感染病例进行队列研究。评估临床特征、危险因素和全病程死亡率。进行全基因组测序和药敏试验。
在187例产ESBL-E血流感染患者中，39.57%（74/187）为BnESBL-E血流感染。医院感染占BnESBL-E血流感染的63.51%，39.19%的病例源自腹腔内感染源。BnESBL-E血流感染的危险因素包括前3个月内暴露于BLBLIs、过去3个月内入住重症监护病房（ICU）以及血流感染前的住院时间。值得注意的是，菌血症的泌尿道来源是预防BnESBL-E血流感染的保护因素（比值比[OR]，0.177；95%置信区间[CI]，0.049 - 0.647；P = 0.009）。与对BLBLIs敏感的病例相比，BnESBL-E血流感染的28天死亡率更高（31.08%对16.81%；P = 0.031）。多因素分析确定皮特菌血症评分、C反应蛋白（CRP）水平和前3个月内住院是BnESBL-E血流感染相关死亡的危险因素，而症状出现后72小时内接受碳青霉烯类药物治疗可改善生存情况（OR，0.128；95% CI，0.018 - 0.912；P = 0.04）。BnESBL-E分离株未显示克隆传播，并且对阿米卡星、碳青霉烯类药物和替加环素仍高度敏感。经常观察到多种ESBL类型共存，在40.6%的BnESBL-和72.7%的BnESBL-分离株中出现。
鉴于BnESBL-E血流感染的高患病率和死亡率，碳青霉烯类药物可能是治疗非泌尿道产ESBL-E血流感染的更优选择。BnESBL-E代表了一种被低估的临床威胁，需要及时识别危险因素并考虑适当的经验性治疗。
