Central nervous system (CNS) infections, including meningitis, encephalitis, and myelitis cause significant long-term morbidity, mortality and health care costs, with an increased incidence in children. Rapid identification of an infectious agent in the cerebrospinal fluid (CSF) is essential to guiding the targeted use of effective antimicrobials in children with suspected CNS infection. Currently utilized diagnostic techniques are low-yield, slow, and expensive leading to widespread use of unnecessary empiric antimicrobial therapies and increased health care costs. Newly developed multiplex PCR panels allow for rapid identification of the most common organisms to cause CNS infections within one hour. However, optimal implementation strategies to translate these more rapid test results into more rapid, appropriate clinical action are unknown. This project seeks to optimize implementation of new rapid molecular CSF diagnostic technology in a tertiary care children?s hospital in conjunction with real-time antimicrobial stewardship decision support using RE-AIM methodology for implementation and evaluation. The research detailed in this proposal meets the critical unmet need for clinical outcomes and cost-effectiveness data for new rapid diagnostic technologies.
This research aims to develop reproducible and sustainable strategies for implementing rapid diagnostics to optimally impact the clinical care of children through the following specific aims: (1) To optimize a reproducible implementation strategy for rapid cerebrospinal fluid diagnostics in children with suspected central nervous system infection, (2)To measure the impact of a rapid cerebrospinal fluid diagnostics program on the clinical care and health care costs of children with suspected central nervous system infection. This project is the culmination of the candidate?s interest and experience in CNS infections and rapid molecular diagnostic technologies. The overall objective of this career development award is to develop the candidate into an independent principal investigator in clinical research with expertise in the implementation and evaluation of infectious disease diagnostics to facilitate timely and efficient clinical care of children. Through experiential mentored research training and didactic coursework in a doctoral clinical sciences program, essential skills in clinical research, implementation and dissemination science, clinical outcomes, and cost-effectiveness analysis will be developed. The candidate has assembled a multidisciplinary team of mentors and advisors with extensive clinical research experience and topical expertise in the above realms to ensure his success in achieving the stated specific aims and career goals.

Public Health Relevance

This proposal seeks to optimize a reproducible implementation strategy for rapid cerebrospinal fluid diagnostic technology in the clinical setting, in order to improve the care of children with suspected central nervous system infections. Clinical impact and cost-effectiveness will be determined to evaluate this technology and implementation strategy.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Mentored Patient-Oriented Research Career Development Award (K23)
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Microbiology and Infectious Diseases B Subcommittee (MID)
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Brown, Liliana L
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University of Colorado Denver
Schools of Medicine
United States
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Messacar, Kevin; Fischer, Marc; Dominguez, Samuel R et al. (2018) Encephalitis in US Children. Infect Dis Clin North Am 32:145-162
Martin, Jan A; Messacar, Kevin; Yang, Michele L et al. (2017) Outcomes of Colorado children with acute flaccid myelitis at 1 year. Neurology 89:129-137
Messacar, Kevin; Parker, Sarah K; Todd, James K et al. (2017) Implementation of Rapid Molecular Infectious Disease Diagnostics: the Role of Diagnostic and Antimicrobial Stewardship. J Clin Microbiol 55:715-723
Messacar, Kevin; Robinson, Christine C; Pretty, Kristin et al. (2017) Surveillance for enterovirus D68 in colorado children reveals continued circulation. J Clin Virol 92:39-41