Child mortality in the United States is most commonly attributed to trauma and sepsis, the major research focus of our research team at the Children's Hospital of Pittsburgh Site of the National Institutes of Child Health and Development (NICHD) Collaborative Pediatric Critical Care Research Network (CPCCRN). This is a renewal application to continue participation in the third cycle of the NICHD-CPCCRN with the goals of collaboratively supporting existing and new studies developed by the Pediatric Trauma and Critical Illness Branch network and also extending our center's novel work within the CPCCRN in host-pathogen interactions in trauma and sepsis. Over the past 9 years our center has provided 24,000 patients to over 22 CPCCRN studies. Our center's program of research in host-pathogen interactions has led to three CPCCRN approved studies. In the first cycle we showed that trauma patients have a two-fold increased risk of developing nosocomial infection and sepsis compared to non-trauma patients. In the second cycle we commenced the ongoing NIGMS-R01 funded Inflammation Phenotypes in Pediatric Severe Sepsis study (PI: Carcillo) which examines the influence of host inflammation phenotype response on nosocomial infection and sepsis outcomes in trauma and non-trauma patients. In our new concept proposal for this third cycle we respond to the NIH roadmap initiative's call for improved understanding of the role of the microbiome in health and disease by evaluating microbiome perturbations in critical illness. In our single center pilot study we found that critically ill children suffered `dysbiosis with loss of microbiome diversity and site specificity with a tendency to formation of an abundant microorganism (> 30% of the microbiome) which could be found in the patient's room and in the patient two days before the onset of nosocomial infection. If we demonstrate that these findings are generalizable across the CPCCRN then this will open the possibility of a new era of microbiome based medicine for prevention and treatment of nosocomial infection and sepsis in critically injured children.

Public Health Relevance

Presently, doctors wait until critically ill children become infected and then treat these children with antibiotics. In our single site we have found that new microbiome technology allows us to measure good bacteria as well as bad bacteria, and when we find that a single bad bacteria becomes abundant (becomes 30% of all bacteria) then the balance of good vs bad is perturbed and the child goes on to develop infection and sepsis with this bad bacteria two or more days later. If we find this to be true across the nation then we will have a new way to recognize, prevent and/or treat at-risk patients before they get overwhelming infection and sepsis.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Clinical Research Cooperative Agreements - Single Project (UG1)
Project #
5UG1HD049983-14
Application #
9394022
Study Section
Special Emphasis Panel (ZHD1)
Program Officer
Maholmes, Valerie
Project Start
2005-05-01
Project End
2019-11-30
Budget Start
2017-12-01
Budget End
2018-11-30
Support Year
14
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Podd, Bradley S; Simon, Dennis W; Lopez, Santiago et al. (2017) Rationale for Adjunctive Therapies for Pediatric Sepsis Induced Multiple Organ Failure. Pediatr Clin North Am 64:1071-1088
Carcillo, Joseph A; Podd, Bradley; Simon, Dennis W (2017) From febrile pancytopenia to hemophagocytic lymphohistiocytosis-associated organ dysfunction. Intensive Care Med 43:1853-1855
Carcillo, Joseph A; Podd, Bradley; Aneja, Rajesh et al. (2017) Pathophysiology of Pediatric Multiple Organ Dysfunction Syndrome. Pediatr Crit Care Med 18:S32-S45
Newth, Christopher J L; Sward, Katherine A; Khemani, Robinder G et al. (2017) Variability in Usual Care Mechanical Ventilation for Pediatric Acute Respiratory Distress Syndrome: Time for a Decision Support Protocol? Pediatr Crit Care Med 18:e521-e529
Carcillo, Joseph A; Sward, Katherine; Halstead, E Scott et al. (2017) A Systemic Inflammation Mortality Risk Assessment Contingency Table for Severe Sepsis. Pediatr Crit Care Med 18:143-150
Carcillo, Joseph A; Halstead, E Scott; Hall, Mark W et al. (2017) Three Hypothetical Inflammation Pathobiology Phenotypes and Pediatric Sepsis-Induced Multiple Organ Failure Outcome. Pediatr Crit Care Med 18:513-523
Carcillo, Joseph A; Dean, J Michael; Holubkov, Richard et al. (2016) Inherent Risk Factors for Nosocomial Infection in the Long Stay Critically Ill Child Without Known Baseline Immunocompromise: A Post Hoc Analysis of the CRISIS Trial. Pediatr Infect Dis J 35:1182-1186
Holubkov, Richard; Clark, Amy E; Moler, Frank W et al. (2015) Efficacy outcome selection in the therapeutic hypothermia after pediatric cardiac arrest trials. Pediatr Crit Care Med 16:1-10
Pollack, Murray M; Holubkov, Richard; Funai, Tomohiko et al. (2015) Simultaneous Prediction of New Morbidity, Mortality, and Survival Without New Morbidity From Pediatric Intensive Care: A New Paradigm for Outcomes Assessment. Crit Care Med 43:1699-709
Meert, Kathleen L; Keele, Linda; Morrison, Wynne et al. (2015) End-of-Life Practices Among Tertiary Care PICUs in the United States: A Multicenter Study. Pediatr Crit Care Med 16:e231-8

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