Acute bacterial meningitis

Emma C Wall, Jia Mun Chan, Eliza Gil, Robert S Heyderman, Emma C Wall, Jia Mun Chan, Eliza Gil, Robert S Heyderman

Abstract

Purpose of review: Community-acquired bacterial meningitis is a continually changing disease. This review summarises both dynamic epidemiology and emerging data on pathogenesis. Updated clinical guidelines are discussed, new agents undergoing clinical trials intended to reduce secondary brain damage are presented.

Recent findings: Conjugate vaccines are effective against serotype/serogroup-specific meningitis but vaccine escape variants are rising in prevalence. Meningitis occurs when bacteria evade mucosal and circulating immune responses and invade the brain: directly, or across the blood-brain barrier. Tissue damage is caused when host genetic susceptibility is exploited by bacterial virulence. The classical clinical triad of fever, neck stiffness and headache has poor diagnostic sensitivity, all guidelines reflect the necessity for a low index of suspicion and early Lumbar puncture. Unnecessary cranial imaging causes diagnostic delays. cerebrospinal fluid (CSF) culture and PCR are diagnostic, direct next-generation sequencing of CSF may revolutionise diagnostics. Administration of early antibiotics is essential to improve survival. Dexamethasone partially mitigates central nervous system inflammation in high-income settings. New agents in clinical trials include C5 inhibitors and daptomycin, data are expected in 2025.

Summary: Clinicians must remain vigilant for bacterial meningitis. Constantly changing epidemiology and emerging pathogenesis data are increasing the understanding of meningitis. Prospects for better treatments are forthcoming.

Trial registration: ClinicalTrials.gov NCT03480191.

Conflict of interest statement

There are no conflicts of interest.

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

Figures

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Box 1
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FIGURE 1
FIGURE 1
Model of BBB environment during bacterial meningitis. ABM pathogen (depicted here as blue diplococci) in the bloodstream cross the capillary endothelium using both transcellular and paracellular routes. Bacteria may also be carried across the BBB by infiltrating phagocytes (Trojan Horse strategy). Recognition of the pathogen via sensing of PAMPs leads to the activation of resident immune cells such as microglia, macrophages, astrocytes and pericytes and production of DAMPs. These cells produce a coordinated inflammatory response to contain bacteria and recruit more neutrophils to the CSF compartment. This host response, while important for killing bacteria, activates a fibrinolytic and coagulation cascade. When advanced, these processes lead to sustained tissue damage, BBB breakdown and leakage, causing death or lifelong neurological sequalae in survivors. ABM, acute bacterial meningitis; BBB, blood–brain barrier.

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Source: PubMed

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