Host defense and antimicrobial therapy in adult gram-negative bacillary meningitis.

Effective therapy for aerobic gram-negative bacillary meningitis is limited by antibiotic resistance among many pathogens and by poor diffusion of some antibiotics into the subarachnoid space. The host response to suppurative meningitis caused by all encapsulated bacteria is impaired by a deficiency of complement and opsonic activity in infected spinal fluid; consequently, therapy with bactericidal antibiotics is preferred. Chloramphenicol diffuses well into cerebrospinal fluid, but is bacteristatic against enteric gram-negative bacilli. Although aminoglycosides are bactericidal, their use requires daily intralumbar or intraventricular injections. Newer cephalosporin compounds, moxalactam and cefotaxime, are bactericidal at very low concentrations and diffuse well from serum to infected spinal fluid. Clinical trials with moxalactam suggest that it is the most effective regimen for enteric gram-negative bacillary meningitis in adults; Pseudomonas aeruginosa and acinetobacter meningitis are most susceptible to a combination of intravenous ticarcillin and aminoglycoside, plus intrathecal aminoglycoside.