Clinicopharmacological evaluation of amoxicillin and probenecid against bacterial meningitis

Forty-three infants and children with bacterial meningitis were treated intravenously with 200 mg of amoxicillin sodium per kg per day for 10 days. (Patients were initially treated with ampicillin and chloramphenicol until the bacterial etiology was defined.) Patients were randomly treated with amoxicillin only or with amoxicillin and four doses of probenecid (10 mg/kg per dose) orally every 6 h for 24 h before the lumbar puncture at day 10. Serum and cerebrospinal fluid (CSF) were obtained on days 1, 5 and 10 of therapy for antibiotic assay. The mean peak serum concentration of amoxicillin of 49.2 μg/ml was increased to 61.4 μg/ml in patients who received probenecid. The half-life in serum (1.5 h) and area under the curve with probenecid (112.5 μg/ml.h) were increased compared with those of amoxicillin alone (1.3 h and 82.2 μg/ml.h). The mean peak CSF concentrations on days 1 and 5 were similar, but day 1 concentrations remained between 2.0 μg/ml and 5.0 μg/ml throughout the 4 h after a dose, whereas the day 5 values decreased at the same decay rate as that in serum. All CSF concentrations were lower on day 10, but patients receiving probenecid had peak values occurring at 1 h rather than at 0.5 h, and levels were significantly greater at 1 and 2 h after a dose. There were no deaths and patients responded well to treatment.