Neonatal Meningitis: Overcoming Challenges in Diagnosis, Prognosis, and Treatment with Omics

Abstract

Neonatal meningitis is a devastating condition. Prognosis has not improved in decades, despite the advent of improved antimicrobial therapy and heightened index of suspicion among clinicians caring for affected infants. One in ten infants die from meningitis, and up to half of survivors develop significant lifelong complications, including seizures, impaired hearing and vision, and delayed or arrested development of such basic skills as talking and walking. At present, it is not possible to predict which infants will suffer poor outcomes. Early treatment is critical to promote more favorable outcomes, though diagnosis of meningitis in infants is technically challenging, time-intensive, and invasive. Profound neuronal injury has long been described in the setting of neonatal meningitis, as has elevated levels of many pro- and anti-inflammatory cytokines. Mechanisms of the host immune response that drive clearance of the offending organism and underlie brain injury due to meningitis are not well understood, however. In this review, we will discuss challenges in diagnosis, prognosis, and treatment of neonatal meningitis. We will highlight transcriptomic, proteomic, and metabolomic data that contribute to suggested mechanisms of inflammation and brain injury in this setting with a view toward fruitful areas for future investigation.

Keywords: cytokines; meningitis; metabolomics; neonatology; proteomics; transcriptomics.

Figure 1

Bacterial meningitis of the neonate leads to profound brain injury, characterized by cortical necrosis and hippocampal apoptosis. Selected transcripts (highlighted in red), cytokines (highlighted in blue), other proteins (highlighted in purple), and metabolites (highlighted in green) identified from omics analyses have been integrated into a proposed model of immune activation in the setting of bacterial meningitis.