Pharmacokinetics and clinical evaluation of cefotaxime in children suffering with purulent meningitis.

Seventy-five children with bacterial meningitis were included in a multicentre trial for evaluation of cerebrospinal fluid (CSF) pharmacokinetics and clinical efficacy of cefotaxime. Mean age of patients was 4 years. Causative pathogens were Haemophilus influenzae in 28 patients (37%), Neisseria meningitidis in 27 patients (36%), Streptococcus pneumoniae in 10 patients (13%), group B streptococcus in 2 patients (2%) and unknown in 8 patients. All isolated pathogens were susceptible to cefotaxime. Seven ampicillin-resistant H. influenzae (9.4%) were found. Cefotaxime was 50 mg/kg intravenously, 4 times daily. The duration of treatment ranged from 5 to 22 days (mean: 13.8). Blood and CSF concentrations of cefotaxime were performed in 50 patients 3 h after infusion at day one and seven cefotaxime levels were determinated both by microbiological assay procedure and high pressure liquid chromatography. On day 1, CSF levels ranged from 0.39 to 2.0 mg/l by microbiological assay procedure (median 3.6) and from 0.0 to 17.4 mg/l (median 2.2) for cefotaxime and from 0.0 to 11.5 mg/l (median 2.2) for desacetyl-cefotaxime by HPLC. We observed a decrease in CSF levels of cefotaxime on day 7. They ranged from 0.3 to 7.0 mg/l (median 1.1) by microbiological assay and from 0.0 to 3.3 mg/l (median 0.8) for cefotaxime and from 0.0 to 6.0 mg/l (median 1.0) for desacetyl-cefotaxime by HPLC. On day 1 and day 7, CSF levels determined by microbiological assay and HPLC were correlated as follows: day 1:r = 0.59 (P less than 0.001). All children (100%) were cured and efficacy of cefotaxime was excellent in 72 cases (96%).(ABSTRACT TRUNCATED AT 250 WORDS)