Cefotaxime and
ceftriaxone have proven to be effective in pyogenic
infections of the central nervous system. Since in some bacterial
central nervous system infections the blood-cerebrospinal fluid (CSF) barrier is either minimally impaired or recovers in the course of the illness, we studied the penetration of both
antibiotics in the absence of inflamed meninges. Patients who had undergone external
ventriculostomies for noninflammatory occlusive
hydrocephalus received either
cefotaxime (2 g/30 min) or
ceftriaxone (2 g/30 min) to treat extracerebral
infections. Serum and CSF were drawn repeatedly after the first dose. With
ceftriaxone, they were also drawn after the last dose. The concentrations of
cefotaxime, its metabolite
desacetylcefotaxime, and
ceftriaxone were determined by high-performance liquid chromatography with UV detection. Maximum concentrations of
cefotaxime in CSF were reached 0.5 to 8 h (median = 3 h; n = 6) after the end of the infusion and ranged from 0.14 to 1.81 mg/liter (median = 0.44 mg/liter; n = 6). Maximum levels of
ceftriaxone in CSF ranging from 0.18 to 1.04 mg/liter (median = 0.43 mg/liter; n = 5) were seen 1 to 16 h (median = 12 h; n = 5) after the infusion. The elimination half-life of
cefotaxime in CSF was 5.0 to 26.9 h (median = 9.3 h; n = 5), and that of
ceftriaxone was 15.7 to 18.4 h (median = 16.8 h; n = 3). It is concluded that after a single dose of 2 g, maximal concentrations of
cefotaxime and
ceftriaxone in CSF do not differ substantially. The long elimination half-lives guarantee uniform concentrations in CSF. These concentrations reliably inhibit highly susceptible bacteria but cannot be relied on to inhibit staphylococci and
penicillin G-resistant Streptococcus pneumoniae.