Pathogenesis and pathophysiology of bacterial meningitis
- Author:
- Rodrigo Hasbun, MD, MPH, FIDSA
- Section Editors:
- Allan R Tunkel, MD, PhD, MACP
- Sheldon L Kaplan, MD
- Deputy Editor:
- Jennifer Mitty, MD, MPH
INTRODUCTION
From its original recognition in 1805 until the early 1900s, bacterial meningitis due to Haemophilus influenzae and Streptococcus pneumoniae was virtually 100 percent fatal. In 1913, Simon Flexner's introduction of intrathecal meningococcal antiserum decreased the mortality of meningococcal meningitis from 75 to 31 percent, but the clinical outcome did not dramatically improve for all three meningeal pathogens until the advent of systemic antimicrobial therapy in the 1930s [1].Despite the effectiveness of antibiotics in clearing bacteria from the cerebrospinal fluid (CSF), bacterial meningitis in adults continues to cause significant morbidity and mortality worldwide. As an example, in the largest prospective study to date of 1412 episodes of community-acquired bacterial meningitis, the case-fatality rate was 17 percent, and unfavorable outcomes occurred in 38 percent [2]. (See "Neurologic complications of bacterial meningitis in adults".)
The pathogenesis and pathophysiology of bacterial meningitis involve a complex interplay between virulence factors of the pathogens and the host immune response [3,4]. Much of the damage from this infection is believed to result from cytokines released within the CSF as the host mounts an inflammatory response. (See "Neurologic complications of bacterial meningitis in adults".)
The clinically important issues related to the pathogenesis and pathophysiology of bacterial meningitis will be reviewed here. The clinical features, treatment, prognosis, and prevention of bacterial meningitis in adults and children and issues related to chronic and recurrent meningitis are discussed separately. (See "Clinical features and diagnosis of acute bacterial meningitis in adults" and "Initial therapy and prognosis of bacterial meningitis in adults" and "Treatment of bacterial meningitis caused by specific pathogens in adults" and "Bacterial meningitis in children older than one month: Clinical features and diagnosis" and "Bacterial meningitis in children older than one month: Treatment and prognosis" and "Approach to the patient with chronic meningitis" and "Approach to the adult with recurrent infections", section on 'Meningitis'.)
PATHOGENESIS
Bacterial meningitis develops when virulence factors of the pathogen overcome host defense mechanisms [3,5].To continue reading this article, you must log in with your personal, hospital, or group practice subscription.
Literature review current through: Apr 2022. | This topic last updated: Dec 09, 2021.
This generalized information is a limited summary of diagnosis, treatment, and/or medication information. It is not meant to be comprehensive and should be used as a tool to help the user understand and/or assess potential diagnostic and treatment options. It does NOT include all information about conditions, treatments, medications, side effects, or risks that may apply to a specific patient. It is not intended to be medical advice or a substitute for the medical advice, diagnosis, or treatment of a health care provider based on the health care provider's examination and assessment of a patient's specific and unique circumstances. Patients must speak with a health care provider for complete information about their health, medical questions, and treatment options, including any risks or benefits regarding use of medications. This information does not endorse any treatments or medications as safe, effective, or approved for treating a specific patient. UpToDate, Inc. and its affiliates disclaim any warranty or liability relating to this information or the use thereof.
The use of this information is governed by the Terms of Use, available at https://www.wolterskluwer.com/en/know/clinical-effectiveness-terms ©2022 UpToDate, Inc. and its affiliates and/or licensors. All rights reserved.
REFERENCES
- Schwentker FF, Gelman S, Long PH. Landmark article April 24, 1937. The treatment of meningococcic meningitis with sulfanilamide. Preliminary report. By Francis F. Schwentker, Sidney Gelman, and Perrin H. Long. JAMA 1984; 251:788.
- Bijlsma MW, Brouwer MC, Kasanmoentalib ES, et al. Community-acquired bacterial meningitis in adults in the Netherlands, 2006-14: a prospective cohort study. Lancet Infect Dis 2016; 16:339.
- McGill F, Heyderman RS, Panagiotou S, et al. Acute bacterial meningitis in adults. Lancet 2016; 388:3036.
- van de Beek D, Brouwer M, Hasbun R, et al. Community-acquired bacterial meningitis. Nat Rev Dis Primers 2016; 2:16074.
- Doran KS, Fulde M, Gratz N, et al. Host-pathogen interactions in bacterial meningitis. Acta Neuropathol 2016; 131:185.
- Kim KS. Investigating Bacterial Penetration of the Blood-Brain Barrier for the Pathogenesis, Prevention, and Therapy of Bacterial Meningitis. ACS Infect Dis 2020; 6:34.
- Plaut AG. The IgA1 proteases of pathogenic bacteria. Annu Rev Microbiol 1983; 37:603.
- Stephens DS, Farley MM. Pathogenic events during infection of the human nasopharynx with Neisseria meningitidis and Haemophilus influenzae. Rev Infect Dis 1991; 13:22.
- Quagliarello V. Dissemination of Neisseria meningitidis. N Engl J Med 2011; 364:1573.
- Picard C, von Bernuth H, Ghandil P, et al. Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency. Medicine (Baltimore) 2010; 89:403.
- Read RC. Neisseria meningitidis; clones, carriage, and disease. Clin Microbiol Infect 2014; 20:391.
- Weinberger DM, Harboe ZB, Sanders EA, et al. Association of serotype with risk of death due to pneumococcal pneumonia: a meta-analysis. Clin Infect Dis 2010; 51:692.
- Tazi A, Disson O, Bellais S, et al. The surface protein HvgA mediates group B streptococcus hypervirulence and meningeal tropism in neonates. J Exp Med 2010; 207:2313.
- Kim KS. Pathogenesis of bacterial meningitis: from bacteraemia to neuronal injury. Nat Rev Neurosci 2003; 4:376.
- Agarwal S, Vasudhev S, DeOliveira RB, Ram S. Inhibition of the classical pathway of complement by meningococcal capsular polysaccharides. J Immunol 2014; 193:1855.
- Kasanmoentalib ES, Valls Serón M, Engelen-Lee JY, et al. Complement factor H contributes to mortality in humans and mice with bacterial meningitis. J Neuroinflammation 2019; 16:279.
- Johswich KO, Zhou J, Law DK, et al. Invasive potential of nonencapsulated disease isolates of Neisseria meningitidis. Infect Immun 2012; 80:2346.
- Daum RS, Scheifele DW, Syriopoulou VP, et al. Ventricular involvement in experimental Hemophilus influenzae meningitis. J Pediatr 1978; 93:927.
- Prager O, Friedman A, Nebenzahl YM. Role of neural barriers in the pathogenesis and outcome of Streptococcus pneumoniae meningitis. Exp Ther Med 2017; 13:799.
- Orihuela CJ, Mahdavi J, Thornton J, et al. Laminin receptor initiates bacterial contact with the blood brain barrier in experimental meningitis models. J Clin Invest 2009; 119:1638.
- Bernard SC, Simpson N, Join-Lambert O, et al. Pathogenic Neisseria meningitidis utilizes CD147 for vascular colonization. Nat Med 2014; 20:725.
- Coureuil M, Bourdoulous S, Marullo S, Nassif X. Invasive meningococcal disease: a disease of the endothelial cells. Trends Mol Med 2014; 20:571.
- Koedel U, Scheld WM, Pfister HW. Pathogenesis and pathophysiology of pneumococcal meningitis. Lancet Infect Dis 2002; 2:721.
- Koelman DLH, Brouwer MC, van de Beek D. Targeting the complement system in bacterial meningitis. Brain 2019; 142:3325.
- Kasanmoentalib ES, Seron MV, Ferwerda B, et al. Erratum to: Mannose-binding lectin-associated serine protease 2 (MASP-2) contributes to poor disease outcome in humans and mice with pneumococcal meningitis. J Neuroinflammation 2017; 14:77.
- Chiavolini D, Pozzi G, Ricci S. Animal models of Streptococcus pneumoniae disease. Clin Microbiol Rev 2008; 21:666.
- Tuomanen E, Tomasz A, Hengstler B, Zak O. The relative role of bacterial cell wall and capsule in the induction of inflammation in pneumococcal meningitis. J Infect Dis 1985; 151:535.
- Tuomanen E, Liu H, Hengstler B, et al. The induction of meningeal inflammation by components of the pneumococcal cell wall. J Infect Dis 1985; 151:859.
- Schneider O, Michel U, Zysk G, et al. Clinical outcome in pneumococcal meningitis correlates with CSF lipoteichoic acid concentrations. Neurology 1999; 53:1584.
- Brouwer MC, Heckenberg SG, de Gans J, et al. Nationwide implementation of adjunctive dexamethasone therapy for pneumococcal meningitis. Neurology 2010; 75:1533.
- Hasbun R, Rosenthal N, Balada-Llasat JM, et al. Epidemiology of Meningitis and Encephalitis in the United States, 2011-2014. Clin Infect Dis 2017; 65:359.
- Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004; 39:1267.
- Bewersdorf JP, Grandgirard D, Koedel U, Leib SL. Novel and preclinical treatment strategies in pneumococcal meningitis. Curr Opin Infect Dis 2018; 31:85.
- Grandgirard D, Gäumann R, Coulibaly B, et al. The causative pathogen determines the inflammatory profile in cerebrospinal fluid and outcome in patients with bacterial meningitis. Mediators Inflamm 2013; 2013:312476.
- Moser R, Schleiffenbaum B, Groscurth P, Fehr J. Interleukin 1 and tumor necrosis factor stimulate human vascular endothelial cells to promote transendothelial neutrophil passage. J Clin Invest 1989; 83:444.
- Quagliarello V, Scheld WM. Bacterial meningitis: pathogenesis, pathophysiology, and progress. N Engl J Med 1992; 327:864.
- Grandgirard D, Schürch C, Cottagnoud P, Leib SL. Prevention of brain injury by the nonbacteriolytic antibiotic daptomycin in experimental pneumococcal meningitis. Antimicrob Agents Chemother 2007; 51:2173.
- Engelen-Lee JY, Brouwer MC, Aronica E, van de Beek D. Pneumococcal meningitis: clinical-pathological correlations (MeninGene-Path). Acta Neuropathol Commun 2016; 4:26.