PASSAGE OF CEFOTAXIME AND CEFTRIAXONE INTO CEREBROSPINAL-FLUID OF PATIENTS WITH UNINFLAMED MENINGES

Cefotaxime and ceftriaxone have proven to be effective in pyogenic inf ections 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 inf lamed 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 infec tions. Serum and CSF were drawn repeatedly after the first dose. With ceftriaxone, they were also drawn after the last dose. The concentrati ons of cefotaxime, its metabolite desacetylcefotaxime, and ceftriaxone were determined by high-performance liquid chromatography with UV det ection. Maximum concentrations of cefotaxime in CSF were reached 0.5 t o 8 h (median = 3 h; n = 6) after the end of the infusion and ranged f rom 0.14 to 1.81 mg/liter (median = 0.44 mg/liter; n = 6). Maximum lev els 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) afte r 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 t o 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 guara ntee uniform concentrations in CSF. These concentrations reliably inhi bit highly susceptible bacteria but cannot be relied on to inhibit sta phylococci and penicillin G-resistant Streptococcus pneumoniae.