Ceftazidime has proven to be effective for the treatment of
bacterial meningitis caused by multiresistant gram-negative bacteria. Since nosocomial
central nervous system infections are often accompanied by only a minor dysfunction of the blood-cerebrospinal fluid (CSF) barrier, patients with noninflammatory occlusive
hydrocephalus who had undergone external
ventriculostomy were studied (n = 8). Serum and CSF were drawn repeatedly after the administration of the first dose of
ceftazidime (3 g over 30 min intravenously), and concentrations were determined by high-performance liquid chromatography by using UV detection. The concentrations of
ceftazidime in CSF were maximal at 1 to 13 h (median, 5.5 h) after the end of the infusion and ranged from 0.73 to 2.80 mg/liter (median, 1.56 mg/liter). The elimination half-lives were 3.13 to 18.1 h (median, 10.7 h) in CSF compared with 2.02 to 5.24 h (median, 3.74 h) in serum. The ratios of the areas under the concentration-time curves in CSF and serum (AUCCSF/AUCS) ranged from 0.027 to 0.123 (median, 0.054). After the administration of a single dose of 3 g, the maximum concentrations of
ceftazidime in CSF were approximately four times higher than those after the administration of 2-g intravenous doses of
cefotaxime (median, 0.44 mg/liter) and
ceftriaxone (median, 0.43 mg/liter) (R. Nau, H. W. Prange, P. Muth, G. Mahr, S. Menck, H. Kolenda, and F. Sörgel, Antimicrob. Agents Chemother. 37:1518-1524, 1993). The median AUCCSF/AUCS ratio of
ceftazidime was slightly below that of
cefotaxime (0.12), but it was 1 order of magnitude above the median AUCCSF/AUCS of
ceftriaxone (0.007) (Nau et al., Antimicrob. Agents Chemother. 37:1518-1524, 1993). The concentrations of
ceftazidime observed in CSF were above the MICs for most Pseudomonas aeruginosa strains. However, they are probably not high enough to be rapidly bactericidal. For this reason, the daily dose should be increased to 12 g in cases of P. aeruginosa
infections of the central nervous system when the blood-CSF barrier is minimally impaired.