Pathophysiology
Clinical meaning
Bacterial meningitis is a medical emergency in which pathogenic organisms (Streptococcus pneumoniae, Neisseria meningitidis, Listeria monocytogenes, Haemophilus influenzae) invade the subarachnoid space and multiply rapidly in the immunologically privileged cerebrospinal fluid. Bacterial cell wall components (lipopolysaccharide, peptidoglycan, teichoic acid) trigger a massive inflammatory cascade: resident macrophages and microglia release tumor necrosis factor-alpha and interleukin-1, which recruit neutrophils and increase blood-brain barrier (BBB) permeability, producing vasogenic edema. Antibiotic-induced bacterial lysis paradoxically releases a burst of cell wall fragments that amplifies this inflammatory response โ this is the pathophysiological basis for adjunctive dexamethasone therapy. Dexamethasone, administered 15-20 minutes before or with the first antibiotic dose, suppresses the inflammatory cascade by inhibiting NF-kB, phospholipase A2, and pro-inflammatory cytokine production, reducing BBB disruption, cerebral edema, and neuronal damage. Clinical evidence demonstrates that dexamethasone reduces mortality in pneumococcal meningitis and hearing loss in H. influenzae meningitis, but provides no benefit if administered more than one hour after the first antibiotic dose (the inflammatory surge has already occurred). Empiric antibiotic selection is age-based: adults 18-50 years receive ceftriaxone plus vancomycin (covering penicillin-resistant pneumococcus); adults over 50...