Empiric therapy for bacterial meningitis.

Population studies from three counties indicate that meningitis occurs with a frequency of approximately 10 episodes per 100,000 population annually in the United States. Estimates based on this prevalence and a population of 2.3 X 10(8) suggest that approximately 23,000 episodes of meningitis occur annually in the United States. Available studies indicate that rapid and reasonably accurate identification of the etiologic agent can be made in greater than or equal to 75% of patients with meningitis by gram-staining of the cerebrospinal fluid, counterimmunoelectrophoresis, or other antigen detection techniques. These means of rapid diagnosis theoretically leave only approximately 7,000 episodes of meningitis annually in the United States in which empiric, as opposed to specific, therapy is necessary. Age-dependent variation in etiologic agents of meningitis markedly influences selection of therapeutic regimens. The preponderance of Enterobacteriaceae and group B streptococci as causes of meningitis in neonates has resulted in utilization of a penicillin (often ampicillin) combined with an aminoglycoside for empiric therapy. Continued high morbidity and mortality, especially in neonatal meningitis caused by Enterobacteriaceae, have been felt to reflect inadequate penetration of aminoglycosides into the cerebrospinal fluid, but careful prospective randomized studies of intrathecal and intraventricular administration of aminoglycosides failed to demonstrate any enhancement of therapeutic results. Ampicillin appeared to be an ideal agent for empiric therapy in older children, in whom meningitis is usually caused by Haemophilus influenzae, with Streptococcus pneumoniae and Neisseria meningitidis being less frequently implicated as etiologic agents. The occurrence of beta-lactamase-mediated resistance to ampicillin in as high as 15% of isolates of H. influenzae has resulted in combined use of ampicillin and chloramphenicol for meningitis in children. This approach is complicated by evidence of clinically important antagonism between ampicillin and chloramphenicol. Since almost all community-acquired meningitis in otherwise healthy adults is caused by meningococci and pneumococci, penicillin remains the agent of choice. In contrast, meningitis following trauma to and surgery involving the central nervous system and in the elderly is often caused by gram-negative bacilli and other "unusual" organisms; therapeutic problems in this group parallel those observed in neonatal meningitis.