The candidates long-term goal is to explore novel therapeutic strategies to improve clinical outcomes in patients with sepsis by investigating the role of macrolide therapy as an immunomodulator. The proposed career development plan integrates didactic coursework and tutorials with mentored research experience in the design and conduct of pharmacoepidemiological and randomized control trials to provide the candidate the necessary components for a successful career in patient-oriented research. The candidate's educational aims are to 1) acquire sufficient knowledge to conduct pharmacoepidemiology studies using large secondary databases and randomized control trials to study the effect of novel immunomodulators for patients with sepsis;2) understand the potential physiologic and genetic mechanisms of novel immunomodulatory treatments;3) translate research findings into clinical practice with the goal of improving the short and long term outcomes of patients with sepsis. Under the mentorship of Drs. Anzueto, Coalson and Mortensen, the candidate will acquire the knowledge and skills required to investigate the effects of macrolide therapy as an immunomodulator in patients with sepsis. The objective of the proposed research is to examine whether the use of a macrolide in addition to standard therapy is associated with improved host immune response, and how this response will impact short and long-term clinical outcomes. The central hypothesis is that macrolide use in patients with pulmonary and extrapulmonary sources of severe sepsis is associated with improved immune response and other clinical outcomes. This proposal will facilitate and provide pilot data for future studies that will evaluate the potential impact of immunomodulatory therapies on improving clinical outcomes for patients with severe sepsis.
Three research aims will be examined: 1) The association between macrolide therapy and clinical outcomes, including short (30-day) and long-term (3, 6 and 12 months) mortality, length of stay, and rates of mechanical ventilation for patients with severe sepsis;2) The effects of macrolide therapy on inflammatory markers and clinical outcomes in patients with severe sepsis;3) The impact of macrolide use vs. non-use on long-term inflammatory markers and survival in patients with severe sepsis. The approach is innovative, because it utilizes macrolides as immunomodulators for an indication other than community-acquired pneumonia in order to improve outcomes in patients with severe sepsis. The proposed research is significant, because it will improve the level of understanding of the possible mechanisms of immunomodulation and the impact of macrolide therapy in patients with severe infections.

Public Health Relevance

This proposal will provide pilot data for future studies that will evaluate the potential impact of immunomodulatory therapies on improving clinical outcomes for patients with severe sepsis and other serious infectious diseases. (End of Abstract)

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL096054-04
Application #
8477237
Study Section
Special Emphasis Panel (ZHL1-CSR-R (O1))
Program Officer
Colombini-Hatch, Sandra
Project Start
2010-08-01
Project End
2015-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
4
Fiscal Year
2013
Total Cost
$137,700
Indirect Cost
$10,200
Name
University of Texas Health Science Center San Antonio
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Amalakuhan, B; Echevarria, K L; Restrepo, M I (2017) Managing community acquired pneumonia in the elderly - the next generation of pharmacotherapy on the horizon. Expert Opin Pharmacother 18:1039-1048
Ruiz, Luis A; España, Pedro P; Gómez, Ainhoa et al. (2017) Age-related differences in management and outcomes in hospitalized healthy and well-functioning bacteremic pneumococcal pneumonia patients: a cohort study. BMC Geriatr 17:130
Wiemken, Timothy L; Kelley, Robert R; Fernandez-Botran, Rafael et al. (2017) Using cluster analysis of cytokines to identify patterns of inflammation in hospitalized patients with community-acquired pneumonia: a pilot study. Univ Louisville J Respir Infect 1:3-11
Reyes, Luis F; Restrepo, Marcos I; Hinojosa, Cecilia A et al. (2017) Severe Pneumococcal Pneumonia Causes Acute Cardiac Toxicity and Subsequent Cardiac Remodeling. Am J Respir Crit Care Med 196:609-620
Kalil, Andre C; Metersky, Mark L; Klompas, Michael et al. (2016) Executive Summary: Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 63:575-82
Cubo-Romano, Pilar; Torres-Macho, Juan; Soni, Nilam J et al. (2016) Admission inferior vena cava measurements are associated with mortality after hospitalization for acute decompensated heart failure. J Hosp Med 11:778-784
Sibila, Oriol; Garcia-Bellmunt, Laia; Giner, Jordi et al. (2016) Airway Mucin 2 Is Decreased in Patients with Severe Chronic Obstructive Pulmonary Disease with Bacterial Colonization. Ann Am Thorac Soc 13:636-42
Cho, Jinmyoung; Copeland, Laurel A; Stock, Eileen M et al. (2016) Protective and Risk Factors for 5-Year Survival in the Oldest Veterans: Data from the Veterans Health Administration. J Am Geriatr Soc 64:1250-7
Attridge, Russell T; Frei, Christopher R; Pugh, Mary Jo V et al. (2016) Health care-associated pneumonia in the intensive care unit: Guideline-concordant antibiotics and outcomes. J Crit Care 36:265-271
Aliberti, Stefano; Lonni, Sara; Dore, Simone et al. (2016) Clinical phenotypes in adult patients with bronchiectasis. Eur Respir J 47:1113-22

Showing the most recent 10 out of 71 publications