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

Abstract

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.Ninety-two AL patients with EBSI from 2010 to 2015 were included. Enterococcal bloodstream infection was defined by 31 positive blood cultures for Enterococcus faecium or Enterococcus faecalis 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 Enterococcus 324 hours after clearance. Categorical variables were reported as proportions and compared by the χ2 test. Continuous variables were summarized by median and interquartile range (IQR) and compared by the Wilcoxon-Mann-Whitney Test. P values <.05 were considered significant. Whole-genome sequencing was performed on available paired BSI isolates from 7 patients.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 E. faecium R-EBSI isolates became daptomycin-nonsusceptible Enterococcus (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.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.

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Citation

Published Version (Please cite this version)

10.1093/ofid/ofy107

Publication Info

Messina, Julia A, Rohita Sinha, Kimberly Starr, Mehreen Arshad, Barbara D Alexander, Nelson J Chao and Anthony D Sung (2018). Clinical and Genomic Characterization of Recurrent Enterococcal Bloodstream Infection in Patients With Acute Leukemia. Open Forum Infectious Diseases, 5(6). p. ofy107. 10.1093/ofid/ofy107 Retrieved from https://hdl.handle.net/10161/18163.

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Scholars@Duke

Messina

Julia Antoinette Messina

Assistant Professor of Medicine

I am a Transplant Infectious Diseases Physician who specializes in the care of immunocompromised patients including solid organ and bone marrow transplant recipients and patients with HIV. My research interests are in infections and clinical outcomes in patients with hematologic malignancies.

Alexander

Barbara Dudley Alexander

Professor of Medicine

Clinical research related to infectious complications of solid organ and bone marrow transplantation, with a particular interest in the treatment and rapid diagnosis of fungal disease. Training the next generation of Transplant Infectious Disease Physicians is a special focus of mine as the Principal Investigator of our Interdisciplinary T32 Training Program funded the NIH. 

Chao

Nelson Jen An Chao

Donald D. and Elizabeth G. Cooke Cancer Distinguished Research Professor

My research interests are in two broad areas, clinical hematopoietic stem cell and cord blood transplantation and in the laboratory studies related to graft vs. host disease and immune reconstitution. On the clinical side we are currently conducting approximately 50 different clinical protocols ranging from preparatory regimens, supportive care studies and disease specific protocols. Most of these clinical studies are centered around studies of the sources of stem cells and the methods to improve the long term outcome. There are exploratory protocols for novel therapies such as dendritic cell therapy for several malignancies, antiangiogenesis therapy, graft engineering to prevent graft-versus-host disease and antigen specific T cells or non specific NK cells to prevent relapse. Moreover a strong focus of the program is to develop cord-blood transplantation for adult patients with hematologic malignancies. The laboratory studies center on understanding the immunological events that occur with graft-vs-host disease and methods to prevent this disease. The current efforts focus on understanding murine reconstitution following transplantation, use of a peptide polymer to block MHC class II recognition of minor histocompatibility antigens, use of T cell engineering to prevent graft-versus-host disease at the same time preserving a graft-versus-malignancy effect.

For more information see http://ed-media.mc.duke.edu/BMT.nsf

Sung

Anthony D Sung

Associate Professor of Medicine

I am dedicated to the treatment of hematologic malignancies through cellular therapies such as hematopoietic stem cell transplantation (HCT). My research focuses on strategies to reduce complications of HCT and ranges from preclinical studies using murine models of HCT to Phase 1 and Phase 2 clinical trials. Areas of interest include the role of the microbiota (the trillions of bacteria living in and on our bodies), nutrition, and exercise in modulating HCT outcomes such as graft-versus-host disease (GVHD) and infections. In addition to advancing new pharmacological and cellular immunotherapies in support of these goals, we also are developing mobile health technologies (mHealth) to monitor patients at home, both as part of our innovative home transplant program as well as to improve follow up care of all our patients when they return home after transplant.


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