Cerebrospinal fluid bactericidal activity against cephalosporin-resistant Streptococcus pneumoniae in children with meningitis treated with high-dosage cefotaxime

We determined cefotaxime and desacetyl-cefotaxime concentrations in children with bacterial meningitis receiving high-dose cefotaxime (300 mg/kg of body weight/day) and concomitant dexamethasone therapy, The median peak cerebrospinal fluid cefotaxime and desacetyl-cefotaxime concentrations were 4.7 and 8.1 mu g/ml, respectively, In vitro bactericidal activity (>99.9% killing in 6 h) was found in 17 (94%), 13 (72%), and 8 (44%) of 18 cerebrospinal fluid specimens against cefotaxime-susceptible, -intermediate (MIC, 1 mu g/ml), and -resistant (MIC, 4 mu g/ml) strains, respectively, High-dose cefotaxime, while safe, is not reliably sufficient therapy for cephalosporin-nonsusceptible pneumococcal meningitis, and combination therapy is recommended.