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儿童恶性肿瘤及造血干细胞移植后继发肠球菌菌血症:15 年单中心经验。

Enterococcal Bacteremia in Children With Malignancies and Following Hematopoietic Stem Cell Transplantation: A 15-Year Single-Center Experience.

机构信息

From the Pediatric Infectious Diseases.

Pediatric Department.

出版信息

Pediatr Infect Dis J. 2020 Apr;39(4):318-324. doi: 10.1097/INF.0000000000002579.

DOI:10.1097/INF.0000000000002579
PMID:31990889
Abstract

BACKGROUND

Data on enterococcal bacteremia (EB) in immunocompromised children are scarce. We aimed to describe EB in children with hematologic malignancies (HM), solid tumors and/or following allogeneic hematopoietic stem cell transplantation (HSCT) and analyze their ampicillin and vancomycin resistance.

METHODS

We conducted an observational retrospective study in the tertiary-care Hadassah University Medical Center (2001-2015). We collected demographic, clinical and laboratory data on EB and compared ampicillin and vancomycin sensitive with resistant episodes.

RESULTS

Fifty-six of 1123 children developed 74 episodes of EB; 62.1% Enterococcus faecium, 36.5% Enterococcus faecalis; and 1.4% Enterococcus gallinarum. EB developed in 12.1% of HSCT patients, 5.1% of HM, 6.3% of neuroblastoma and 1.0% of other solid tumors patients. Of these episodes, 85.1% were nosocomial, and 71.6% developed while on antibiotic therapy. Resistance rates were: to ampicillin, 57.6%; to vancomycin (vancomycin-resistant enterococci), 21.6%; and higher rates among E. faecium. Among vancomycin-resistant enterococci, 1 of 16 was linezolid and 2 of 10 daptomycin resistant. Overall 7- and 30-day mortality rates were 2.7% and 5.4%, respectively. Thirty-day mortality was 18.2% in recurrent episodes and 0% in the first-time EB episodes (P = 0.006). In multivariate analysis, high treatment intensity was associated with ampicillin resistance [odds ratio (OR) = 3.18, 95% confidence interval (CI): 1.31-9.12], prior penicillin exposure (OR = 7.50, 95% CI: 1.41-39.81) and breakthrough on vancomycin (OR = 18.83, 95% CI: 3.31-101.14) with vancomycin resistance.

CONCLUSIONS

EB occurs mainly as a nosocomial infection in children receiving high-intensity chemotherapy, especially in those with neuroblastoma, HM and following HSCT. Antibiotic resistance is common. Vancomycin resistance can occur regardless of previous vancomycin use. Prognosis in immunocompromised children with EB is better than previously reported. Recurrent EB is associated with increased mortality.

摘要

背景

免疫功能低下儿童的肠球菌菌血症(Enterococcal bacteremia,EB)数据较为匮乏。本研究旨在描述血液系统恶性肿瘤(hematologic malignancies,HM)、实体瘤患儿以及接受异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,HSCT)后的患儿发生 EB 的情况,并分析其氨苄西林和万古霉素耐药情况。

方法

本研究为回顾性观察性研究,在三级医疗中心哈达萨大学医学中心(2001-2015 年)开展。我们收集了 EB 的人口统计学、临床和实验室数据,并比较了氨苄西林和万古霉素敏感与耐药的感染情况。

结果

1123 例患儿中有 56 例发生 74 例 EB;粪肠球菌占 62.1%,屎肠球菌占 36.5%,鸡肠球菌占 1.4%。12.1%的 HSCT 患者、5.1%的 HM 患者、6.3%的神经母细胞瘤患者和 1.0%的其他实体瘤患者发生了 EB。这些感染中有 85.1%为医院获得性感染,71.6%在接受抗生素治疗时发生。耐药率为:氨苄西林 57.6%,万古霉素(耐万古霉素肠球菌)21.6%,粪肠球菌的耐药率更高。耐万古霉素肠球菌中,利奈唑胺耐药 1 例,达托霉素耐药 2 例。总的 7 天和 30 天死亡率分别为 2.7%和 5.4%。复发性 EB 的 30 天死亡率为 18.2%,首次 EB 感染的死亡率为 0%(P=0.006)。多变量分析显示,高强度治疗与氨苄西林耐药相关(比值比[OR]为 3.18,95%置信区间[CI]:1.31-9.12),青霉素暴露史(OR 为 7.50,95%CI:1.41-39.81)和万古霉素治疗中出现突破(OR 为 18.83,95%CI:3.31-101.14)与万古霉素耐药相关。

结论

EB 主要发生在接受高强度化疗的儿童中,尤其是神经母细胞瘤、HM 和接受 HSCT 后的儿童中,且为医院获得性感染。抗生素耐药很常见。无论之前是否使用过万古霉素,都可能出现万古霉素耐药。免疫功能低下儿童 EB 的预后优于之前报道的预后。复发性 EB 与死亡率升高相关。

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