Rationale for clinical trials evaluating ceftriaxone in the therapy of bacterial meningitis

Ceftriaxone is a promising antimicrobial agent in the therapy of bacterial meningitis. The rationale for the clinical evaluation of ceftriaxone in patients with meningitis is based on the following favorable characteristics: ceftriaxone has excellent in vitro activity (MBC90 0.25 microgram/ml or less) against the major meningeal pathogens including meningococci, pneumococci, group B streptococci, Hemophilus influenzae, and Escherichia coli, but it is inactive against Listeria monocytogenes; ceftriaxone is rapidly bactericidal within purulent cerebrospinal fluid in experimental animal models of meningitis induced by pneumococci, group B streptococci, H. influenzae, and E. coli; against most of the major meningeal pathogens, the activity attained in cerebrospinal fluid in human subjects with bacterial meningitis is high (1:512 or greater) and active concentrations of ceftriaxone persist in cerebrospinal fluid for prolonged periods compared with those of other cephalosporins; the results of clinical trials reported to date in patients with meningitis are encouraging. Ceftriaxone deserves further clinical evaluation in the treatment of bacterial meningitis; the optimal dose, frequency of administration, and duration of therapy remain to be determined.