Date of Award

January 2020

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Paul L. Aronson

Abstract

Objectives: The aims of this body of work are several fold. Aim 1: To describe the cerebrospinal fluid (CSF) profile of infants ≤60 days old with bacterial meningitis and characterize the clinical and laboratory features of infants with bacterial meningitis who present with no CSF abnormalities. Aim 2: To evaluate the performance characteristics of the BioFire® FilmArray® Meningitis/Encephalitis panel (ME panel), the only Food and Drug Administration (FDA)-cleared multiplexed panel for the evaluation of CSF samples. Aim 3: To identify themes to be included in a parent-reported outcome measure for febrile infants ≤60 days old and to describe the process of developing a software application for use with parents of febrile infants ≤60 days old evaluated in the emergency department.

Methods: Aim 1: Clinical and laboratory data was abstracted from electronic medical records of infants ≤60 days old with culture-positive bacterial meningitis from 11 children’s hospitals in the U.S. in a 5-year period. Aim 2: A thorough review of the literature was performed to gather data required for the evaluation of the ME panel. Aim 3: Semi-structured qualitative interviews, as well as design impression and usability testing of the software application were conducted with parents of febrile infants ≤60 days old evaluated in the emergency department.

Results: Aim 1: The sensitivity of a CSF Gram stain was 71.9% (95% CI: 59.2–82.4), and the sensitivity of corrected CSF pleocytosis was 80.3% (95% CI: 68.7–89.1) among infants ≤60 days old with bacterial meningitis. Of 9 infants with meningitis who had a negative Gram stain result and no corrected CSF pleocytosis, 8 (88.9%) had either an abnormal peripheral WBC count (>15 000 or <5000 cells per μL) or bandemia >10%. Aim 2: The ME panel has a pooled sensitivity of 90.2% (95% CI: 86.2-93.1) and specificity of 97.7% (95% CI: 94.6-99.0). The overall sensitivity for 5 of the 6 bacterial organisms in the panel was 96.8% (95% CI: 92.7-99.0). Aim 3: After preliminary qualitative data analysis of interviews with parents, themes for the parent-reported outcome measure include feeling informed, involvement in decisions, stress, infant and family outcomes, which emerged as possibilities for further validation. Testing of the software application has identified elements in the structure, navigability and content to be modified prior to field testing.

Conclusions: Aim 1: Infants with no CSF pleocytosis and a negative Gram stain result are unlikely to have bacterial meningitis in the absence of other laboratory abnormalities. Aim 2: The ME panel is a rapid diagnostic tool with an overall high sensitivity and specificity for CNS infections, with potential to improve diagnosis and optimize utilization of healthcare resources. Aim 3: Semi-structured qualitative interviews have allowed for the preliminary identification of themes to be considered for validation in the generation of a parent-reported outcome measure of febrile infants ≤60 days of life. Design impression and usability testing of the application have enabled the identification of changes needed to optimize the effectiveness of the application for parents of febrile infants.

Comments

This thesis is restricted to Yale network users only. It will be made publicly available on 09/10/2021

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