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Few diseases ignite the fear that develops when bacterial meningitis strikes a community. Its potential for communicability and fatality scares families and health care workers alike. Physicians, particularly pediatricians, recognize it as a disease with potentially subtle presentation but devastating consequences if misdiagnosed. Over the last decade, advances in the understanding of pathophysiological aspects of the disease and in vaccine development have provided opportunities to improve outcome but have simultaneously generated controversies regarding therapy because of the rapidly changing epidemiological factors involved. In this review, we highlight the changing perspectives on bacterial meningitis that have evolved as a result of experimental models, clinical intervention trials, and epidemiological trends.

Predisposing conditions for acute bacterial meningitis include prematurity, young age, management in an intensive care setting, low socioeconomic background, and crowded living conditions. Clinical findings vary with age and may be nonspecific (altered feeding behavior) or specific (Kernig and Brudzinski signs). Examination and culture of cerebrospinal fluid (CSF) are essential for diagnosis. Antigen identification in CSF, serum, or urine by latex agglutination or other techniques can be useful in the identification of the pathogen. Randomized, controlled studies with a single-, double-, or evaluator-blinded design are encouraged. Among neonates, infants, and children, CSF should be examined again 24-36 hours after initiation of therapy. Outcomes should be judged by both clinical and microbiological criteria. Assessment of microbiological outcome is paramount.

Viral encephalitis may develop subsequent to viremia, via neuronal spread, or by arthropod vector. Diagnosis often requires invasive studies such as lumbar puncture and brain biopsy. This guideline addresses herpes simplex, rabies, and arbovirus infections of the central nervous system. Clinical trials should be designed according to the availability of approved therapeutic agents. Study designs with an active control (herpesvirus), a placebo control (arbovirus), or no control (rabies virus) are recommended. Outcome should be assessed 4-6 weeks, 4-6 months, and 11-13 months after the completion of therapy. For newborns with encephalitis, outcome should be assessed yearly through the age of 5 years. Assessment of clinical outcome is paramount.

The rationale for use of quinolones in the treatment of central nervous system (CNS) infections is reviewed. Quinolones exert potent activity in vitro against many gram-negative meningeal pathogens. Given the concentrations attained in cerebrospinal fluid (CSF), however, activity against gram-positive organisms is marginal. As a group, the quinolones enter (penetrate) the CSF better than do any other class of antimicrobial agents. The percentage penetration into CSF is remarkably similar in animal models and in humans with meningitis receiving concurrent therapy. The relative rank order for CSF penetration is as follows: enoxacin and pefloxacin (approximately 50%) greater than ciprofloxacin and ofloxacin (approximately 20%-30%). Certain quinolones have proven to be equivalent to conventional agents (e.g., third-generation cephalosporins) in the rate with which they eradicate bacterial gram-negative organisms from the CSF in experimental animal models of meningitis, but the serum concentrations have usually been higher than those achieved in humans. Despite these advantages, the concentrations in CSF remain low (e.g., ciprofloxacin, approximately 0.25-0.5 mg/L; pefloxacin, 4-8 mg/L) in humans because of the relatively low concentrations attained in serum. Thus, quinolones will continue to be most useful in the treatment of infections due to problem pathogens or to multiresistant pathogens (e.g., Pseudomonas species). Although quinolones appear to enter brain tissue readily, it is unlikely that they can be used as single agents for the treatment of brain abscess because of poor activity against anaerobes and streptococci, and no animal or human studies have been reported. A single dose of ciprofloxacin administered orally appears promising for use in eradication of the meningococcal carrier state.