Bacterial Meningitis: Recent Advances in Pathophysiology and Treatment

Abstract

To review recent advances in the understanding of pathogenic and pathophysiologic mechanisms underlying bacterial meningitis that may lead to the development of adjunctive strategies for treating this disorder. Studies published from 1975 to 1989 were identified using Index Medicus and by reviewing the bibliographies of identified articles. We reviewed the experimental and human studies evaluating pathogenesis, pathophysiology, and antimicrobial treatment of bacterial meningitis, as well as those reviews that have contributed to our understanding of meningitis. We evaluated the data on the pathogenesis, pathophysiology, and treatment of bacterial meningitis and considered in depth the information from animal models that may have potentially important applications in the treatment of human disease. Penicillin and ampicillin remain the drugs of choice for meningitis caused by Streptococcus pneumoniae and Neisseria meningitidis. The third-generation cephalosporins have revolutionized the treatment of gram-negative bacillary meningitis; one such agent, ceftazidime, is also useful for treating Pseudomonas aeruginosa meningitis. Modification of subarachnoid space inflammation by anti-inflammatory agents may lessen many of the pathophysiologic consequences of bacterial meningitis. A recent study of adjunctive dexamethasone therapy in infants and children with bacterial meningitis showed that the incidence of long-term neurologic sequelae was lower in the corticosteroid group. Future therapy for bacterial meningitis will use recent developments in the understanding of pathogenic and pathophysiologic mechanisms underlying this disease. Additional studies using monoclonal antibodies against specific virulence factors and investigations into the production of inflammatory cytokines in response to bacterial cell products may lead to additional treatments that decrease the high morbidity and mortality in patients with bacterial meningitis.