Infants in the neonatal ICU (NICU) have a high incidence of bacterial sepsis, predominantly caused by Gram-negative enteric pathogens and staphylococcal species, with antibiotic resistant infections increasing. Symptoms of sepsis in newborns are non-specific, leading to an overuse of antibiotics in this population. Current methods for pathogen detection and antibiotic susceptibility testing are time and labor intensive and often inadequate. Rapid, real-time diagnostics, with the capability to detect, identify and characterize pathogens with respect to antibiotic sensitivities are critically needed for improved patient care, patient outcomes and antibiotic stewardship. This application proposes development of NeoDIRECT (Detection and Identification of Resistance Equals Correct Treatment), a rapid real-time PCR-based diagnostic assay for the detection and identification of the primary pathogens of sepsis in the NICU.
My Specific Aims are: 1) to complete development of NeoDIRECT to include nested-multiplex PCR (nmPCR) to detect and identify the most common pathogens of neonatal sepsis and their genetic determinants of antibiotic resistance, 2) to adapt NeoDIRECT for direct-from-specimen testing using whole blood as a model and 3) perform a clinical study to evaluate the potential impact of NeoDIRECT on vancomycin use in the NICU and a survey to evaluate physician attitudes. Development of NeoDIRECT will be of significant benefit to infants in the NICU and will provide a model for pathogen detection in the "FilmArray", an innovative real-time PCR platform developed at Idaho Technology, Inc., with myriad future applications for hospitalized children and adults. In addition to my research aims, my Specific Career Development Aims include: 1) to expand my existing skills in the development of PCR-based diagnostics, 2) to expand my knowledge about hospital- acquired infection and antibiotic-resistant organisms, 3) to learn about the validation, implementation, and FDA approval of clinical assays, 4) to develop skills in clinical and health services research that will enable me to validate novel diagnostic tests in clinical settings and use them to conduct hypothesis-driven patient- oriented research,5) to develop research management skills to lead future projects and 6) to develop leadership skills through leadership training. Optimal development of new diagnostic technologies will involve an interdisciplinary approach including academia, industry, basic- and clinician- scientists. As a highly- trained physician and scientist-collaborating with biotechnology at the outset of my career-I am uniquely positioned to make significant contributions to this field.

Public Health Relevance

My overarching career goal is to improve the healthcare of children and adults through improved diagnostic testing for infectious agents and antimicrobial resistance. Development of NeoDIRECT will be of significant benefit to infants in the NICU and will provide a model for pathogen detection in the "FilmArray", an innovative real-time PCR platform developed at Idaho Technology, Inc., with myriad future applications for hospitalized children and adults

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AI079401-04
Application #
8214555
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Ritchie, Alec
Project Start
2009-03-01
Project End
2013-06-28
Budget Start
2012-03-01
Budget End
2013-06-28
Support Year
4
Fiscal Year
2012
Total Cost
$137,160
Indirect Cost
$10,160
Name
University of Utah
Department
Pediatrics
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Glissmeyer, Eric W; Korgenski, E Kent; Wilkes, Jacob et al. (2014) Dipstick screening for urinary tract infection in febrile infants. Pediatrics 133:e1121-7
Simon, Tamara D; Van Yserloo, Brian; Nelson, Kevin et al. (2014) Use of quantitative 16S rRNA PCR to determine bacterial load does not augment conventional cerebrospinal fluid (CSF) cultures among children undergoing treatment for CSF shunt infection. Diagn Microbiol Infect Dis 78:188-95
Blaschke, Anne J; Byington, Carrie L; Ampofo, Krow et al. (2013) Species-specific PCR improves detection of bacterial pathogens in parapneumonic empyema compared with 16S PCR and culture. Pediatr Infect Dis J 32:302-3
Doby, Elizabeth H; Benjamin Jr, Daniel K; Blaschke, Anne J et al. (2012) Therapeutic monitoring of voriconazole in children less than three years of age: a case report and summary of voriconazole concentrations for ten children. Pediatr Infect Dis J 31:632-5
Stockmann, Chris; Ampofo, Krow; Hersh, Adam L et al. (2012) Evolving epidemiologic characteristics of invasive group a streptococcal disease in Utah, 2002-2010. Clin Infect Dis 55:479-87
Blaschke, Anne J (2011) Interpreting assays for the detection of Streptococcus pneumoniae. Clin Infect Dis 52 Suppl 4:S331-7
Blaschke, Anne J; Allison, Mandy A; Meyers, Lindsay et al. (2011) Non-invasive sample collection for respiratory virus testing by multiplex PCR. J Clin Virol 52:210-4
Blaschke, Anne J; Heyrend, Caroline; Byington, Carrie L et al. (2011) Molecular analysis improves pathogen identification and epidemiologic study of pediatric parapneumonic empyema. Pediatr Infect Dis J 30:289-94
Poritz, Mark A; Blaschke, Anne J; Byington, Carrie L et al. (2011) FilmArray, an automated nested multiplex PCR system for multi-pathogen detection: development and application to respiratory tract infection. PLoS One 6:e26047
Ampofo, Krow; Pavia, Andrew T; Stockmann, Chris R et al. (2011) Evolution of the epidemiology of pneumococcal disease among Utah children through the vaccine era. Pediatr Infect Dis J 30:1100-3

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