Bacterial meningitis is the most common serious infection of the central nervous system (CNS) and leads to significant morbidity and mortality. An improved understanding of the pathogenesis of this condition might lead to advances in management and ultimately improve outcome in patients. This article aims to describe currently held concepts about the pathogenesis of bacterial meningitis from nasopharyngeal acquisition, mucosal invasion and entry into the circulation through to the sequelae of subarachnoid space invasion and inflammation, alterations in cerebral blood flow, the blood-brain barrier and intracranial pressure. Finally, the implications of advances in the understanding of the disease process for adjunctive therapy are discussed.
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References
1.
QuagliarelloV, ScheldWM. Bacterial meningitis: pathogenesis, pathophysiology, and progress. New Engl J Med1992; 327(12):864–72.
2.
PlautAG. The IgA1 proteases of pathogenic bacteria. Annu Rev Microbiol1983; 37:603–22.
3.
TunkelAR, WispelweyB, ScheldWM. Bacterial meningitis: recent advances in pathophysiology and treatment (see comments). Ann Intern Med1990; 112(8):610–23.
QuagliarelloVJ. Recombinant human interleukin-1 induces meningitis and blood-brain barrier injury in the rat. Characterization and comparison with tumor necrosis factor. J Clinical Invest1991; 87(4):1360–6.
6.
HandaS. Concentrations of interleukin-1 beta, interleukin-6, interleukin-8 and TNF-alpha in cerebrospinal fluid from children with septic or aseptic meningitis. Kurume Med J1992; 39(4):257–65.
7.
LowPS. Inflammatory response in bacterial meningitis: cytokine levels in the cerebrospinal fluid. Ann Trop Paediatr1995; 15(1):55–9.
8.
CeyhanM. Tumor necrosis factor-alpha and interleukin-1 beta levels in children with bacterial, tuberculous and aseptic meningitis. Turk J Pediatr1997; 39(2):177–84.
9.
TunkelAR, ScheldWM. Pathogenesis and pathophysiology of bacterial meningitis. Annu Rev Med1993; 44:103–20.
10.
KieseierBC. Differential expression of matrix metalloproteinases in bacterial meningitis. Brain1999. 122(Part 8):1579–87.
11.
CauwelsA. The origin and function of soluble CD14 in experimental bacterial meningitis. J Immunol1999; 162(8):4762–72.
12.
MertsolaJ. Endotoxin concentrations in cerebrospinal fluid correlate with clinical severity and neurologic outcome of Haemophilus influenzae type B meningitis. Am J Diseases of Children1991; 145(10):1099–103.
13.
ArditiML, AblesL, YogevR. Cerebrospinal fluid endotoxin levels in children with H. influenzae meningitis before and after administration of intravenous ceftriaxone (see comments). J Infect Dis1989; 160(6):1005–11.
14.
FriedlandIR. Comparison of endotoxin release by different antimicrobial agents and the effect on inflammation in experimental Escherichia coli meningitis (published erratum appears in J Infect Dis1993; 168(5):1342). J Infect Dis 1993; 168(3):657–62.
15.
QuagliarelloVJ. Ultrastructural localization of albumin transport across the cerebral microvasculature during experimental meningitis in the rat. J Exp Med1991; 174(3):657–72.
16.
FassbenderK. Inflammatory cytokines in CSF in bacterial meningitis: association with altered blood flow velocities in basal cerebral arteries. J Neurol Neurosurg Psychiatry1996; 61(1):57–61.
17.
BeggN. Consensus statement on diagnosis, investigation, treatment and prevention of acute bacterial meningitis in immunocompetent adults. J Infect1999; 39(1):1–15.
18.
PfisterHW. Mechanisms of brain injury in bacterial meningitis: workshop summary. Clin Infect Dis1994; 19(3):463–79.
19.
GirgisNI. Dexamethasone treatment for bacterial meningitis in children and adults. Pediatr Infect Dis J1989; 8(12):848–51.
WeissJ. Human bactericidal/permeability-increasing protein and a recombinant NH2–terminal fragment cause killing of serum-resistant gram-negative bacteria in whole blood and inhibit tumor necrosis factor release induced by the bacteria. J Clin Invest1992; 90(3):1122–30.
22.
GiroirBP. Preliminary evaluation of recombinant amino-terminal fragment of human bactericidal/permeability-increasing protein in children with severe meningococcal sepsis (see comments). Lancet1997; 350(9089):1439–43.
