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急性白血病患者复发性肠球菌血流感染的临床与基因组特征

Clinical and Genomic Characterization of Recurrent Enterococcal Bloodstream Infection in Patients With Acute Leukemia.

作者信息

Messina Julia A, Sinha Rohita, Starr Kimberly, Arshad Mehreen, Alexander Barbara D, Chao Nelson J, Sung Anthony D

机构信息

Division of Infectious Diseases, Department of Medicine, Durham, North Carolina.

Division of Hematologic Malignancies and Cellular Therapies, Department of Medicine, Duke University, Durham, North Carolina.

出版信息

Open Forum Infect Dis. 2018 May 5;5(6):ofy107. doi: 10.1093/ofid/ofy107. eCollection 2018 Jun.

Abstract

BACKGROUND

Rates and risk factors for recurrent enterococcal bloodstream infection (R-EBSI) and whether the same genetic lineage causes index EBSI and R-EBSI are unknown in patients with acute leukemia (AL) receiving chemotherapy.

METHODS

Ninety-two AL patients with EBSI from 2010 to 2015 were included. Enterococcal bloodstream infection was defined by 31 positive blood cultures for or and fever, hypotension, or chills. Clearance was defined by 31 negative cultures 324 hours after last positive culture and defervescence. Recurrent enterococcal bloodstream infection was defined by a positive blood culture for 324 hours after clearance. Categorical variables were reported as proportions and compared by the χ test. Continuous variables were summarized by median and interquartile range (IQR) and compared by the Wilcoxon-Mann-Whitney Test. values <.05 were considered significant. Whole-genome sequencing was performed on available paired BSI isolates from 7 patients.

RESULTS

Twenty-four patients (26%) had 31 episodes of R-EBSI. Median time to R-EBSI (IQR) was 26 (13-50) days. Patients with R-EBSI had significantly longer durations of fever and metronidazole exposure during their index EBSI. Thirty-nine percent of R-EBSI isolates became daptomycin-nonsusceptible (DNSE) following daptomycin therapy for index EBSI. Whole-genome sequencing analysis confirmed high probability of genetic relatedness of index EBSI and R-EBSI isolates for 4/7 patients.

CONCLUSIONS

Recurrent enterococcal bloodstream infection and DNSE are common in patients with AL and tend to occur within the first 30 days of index EBSI. Duration of fever and metronidazole exposure may be useful in determining risk for R-EBSI. Whole-genome sequencing analysis demonstrates that the same strain causes both EBSI and R-EBSI in some patients.

摘要

背景

接受化疗的急性白血病(AL)患者中,复发性肠球菌血流感染(R-EBSI)的发生率、危险因素以及引发初次肠球菌血流感染(EBSI)和R-EBSI的是否为同一基因谱系尚不清楚。

方法

纳入2010年至2015年期间92例发生EBSI的AL患者。肠球菌血流感染定义为3次或以上血培养阳性且有 或 ,同时伴有发热、低血压或寒战。清除定义为末次阳性培养后324小时血培养阴性且热退。复发性肠球菌血流感染定义为清除后324小时血培养阳性。分类变量以比例形式报告,并通过χ检验进行比较。连续变量以中位数和四分位数间距(IQR)进行总结,并通过Wilcoxon-Mann-Whitney检验进行比较。P值<.05被认为具有统计学意义。对7例患者可获得的配对血流感染分离株进行全基因组测序。

结果

24例患者(26%)发生了31次R-EBSI发作。R-EBSI的中位时间(IQR)为26(13 - 50)天。发生R-EBSI的患者在初次EBSI期间发热持续时间和甲硝唑暴露时间明显更长。初次EBSI接受达托霉素治疗后,39%的R-EBSI分离株对达托霉素不敏感(DNSE)。全基因组测序分析证实,4/7的患者初次EBSI和R-EBSI分离株具有高度遗传相关性。

结论

复发性肠球菌血流感染和DNSE在AL患者中很常见,且往往发生在初次EBSI的前30天内。发热持续时间和甲硝唑暴露时间可能有助于确定R-EBSI的风险。全基因组测序分析表明,在一些患者中,同一菌株可引发EBSI和R-EBSI。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f56/6016419/292bc4a974b5/ofy10701.jpg

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