Bacteremia in solid organ transplant recipients as compared to immunocompetent patients: Acute phase cytokines and outcomes in a prospective, matched cohort study.
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2021-06
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Abstract
We undertook a prospective, matched cohort study of patients with Staphylococcus aureus bacteremia (SAB) and gram-negative bacteremia (GNB) to compare the characteristics, outcomes, and chemokine and cytokine response in transplant recipients to immunocompetent, nontransplant recipients. Fifty-five transplant recipients (GNB n = 29; SAB n = 26) and 225 nontransplant recipients (GNB n = 114; SAB n = 111) were included for clinical analysis. Transplant GNB had a significantly lower incidence of septic shock than nontransplant GNB (10.3% vs 30.7%, p = .03). Thirty-day mortality did not differ significantly between transplant and nontransplant recipients with GNB (10.3% vs 15.8%, p = .57) or SAB (0.0% vs 11.7%, p = .13). Next, transplant patients were matched 1:1 with nontransplant patients for the chemokine and cytokine analysis. Five cytokines and chemokines were significantly lower in transplant GNB vs nontransplant GNB: IL-2 (median [IQR]: 7.1 pg/ml [7.1, 7.1] vs 32.6 pg/ml [7.1, 88.0]; p = .001), MIP-1β (30.7 pg/ml [30.7, 30.7] vs 243.3 pg/ml [30.7, 344.4]; p = .001), IL-8 (32.0 pg/ml [5.6, 53.1] vs 59.1 pg/ml [39.2, 119.4]; p = .003), IL-15 (12.0 pg/ml [12.0, 12.0] vs 12.0 pg/ml [12.0, 126.7]; p = .03), and IFN-α (5.1 pg/mL [5.1, 5.1] vs 5.1 pg/ml [5.1, 26.3]; p = .04). Regulated upon Activation, Normal T Cell Expressed and Secreted (RANTES) was higher in transplant SAB vs nontransplant SAB (mean [SD]: 750.2 pg/ml [194.6] vs 656.5 pg/ml [147.6]; p = .046).
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Eichenberger, Emily M, Felicia Ruffin, Michael Dagher, Reginald Lerebours, Sin-Ho Jung, Batu Sharma-Kuinkel, Andrew N Macintyre, Joshua T Thaden, et al. (2021). Bacteremia in solid organ transplant recipients as compared to immunocompetent patients: Acute phase cytokines and outcomes in a prospective, matched cohort study. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 21(6). pp. 2113–2122. 10.1111/ajt.16388 Retrieved from https://hdl.handle.net/10161/24331.
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Scholars@Duke
Felicia Ruffin
Reginald (Gino) Lerebours
Education: Masters Degree, Biostatistics. Harvard University. 2017
Bachelors Degree, Statistics. North Carolina State University. 2015
Overview: Gino currently collaborates with researchers, residents, and clinicians in the Departments of Surgery, Radiology and Infectious Diseases. His main research interests and experience are in statistical programming, data management, statistical modeling, statistical consulting and statistical education.
Sin-Ho Jung
Design of Clinical Trials
Survival Analysis
Longitudinal Data Analysis
Clustered Data Analysis
ROC Curve Analysis
Design and Analysis of Microarray Studies
Big Data Analysis
Andrew Neil Macintyre
Andrew Macintyre, PhD, directs the Immunology Unit within the Duke Regional Biocontainment Laboratory. The Macintyre lab team designs and performs assays to quantify immune reconstitution and immune responses. The lab specializes in multiplex cytokine arrays, flow cytometry, high-throughput ELISAs, qRT-PCR, and other molecular tests.
The assays his team develops and runs support research into biodefense and critical public health challenges. Long-running collaborative projects include the evaluation of radiation countermeasures and the development of vaccines for influenza, gonorrhea, SARS-CoV2, and other pathogens.
Joshua Thomas Thaden
Matthew Sinclair
Scott Michael Palmer
Dr. Palmer leads a successful program of clinical, basic and translational research in lung transplantation, idiopathic pulmonary fibrosis (IPF), bronchiolitis obliterans (BO) and other lung diseases. He directs the Medicine Plus Therapeutic Area at the Duke Clinical Research Institute (DCRI) and serves as Vice Chair for Research in the Department of Medicine. He is also the Director of Clinical Research, Duke Transplant Center.
Dr. Palmer has over 250 peer reviewed publications, received numerous awards, including election into the American Society for Clinical Investigation (ASCI) in 2012, chaired many sessions at national and international meetings, serves regularly on NIH study sections, and is on the editorial board of many prominent journals. He is a dedicated mentor to trainees and junior faculty, having personally mentored over 40 pre-and post-doctoral trainees, many of whom are now engaged in their own successful research careers. He is multiple PI on two Duke R38 awards supporting dedicated resident research, and multiple PI for a Duke Pulmonary T32 training program, all reflecting his deep commitment to support and train the next generation of physician investigators. He has received continuous NIH funding since 2002.
His scientific accomplishments include high impact studies that have demonstrated the importance of innate immunity in transplant rejection, a clinical trial that improved cytomegalovirus (CMV) prevention after lung transplantation, and work that identified rare protein coding exome variants that contribute to the development of IPF. In addition to these studies he has led numerous multicenter studies, registries and clinical trials. His program of translational research focuses on the use of human tissue and samples in studying pulmonary transplant rejection, and the use of human airway cells epithelial cells in the study of bronchiolitis obliterans including in the transplant and occupational setting. Recent work has employed single cell RNAseq to discover novel cell types and mechanisms involved in lung disease and transplant rejection.
Vance Garrison Fowler
Determinants of Outcome in Patients with Staphylococcus aureus Bacteremia
Antibacterial Resistance
Pathogenesis of Bacterial Infections
Tropical medicine/International Health
Stacey Ann Maskarinec
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