Serum Concentrations of Cefotaxime and its Metabolite Desacetyl-cefotaxime in Infants and Children During Continuous Infusion

Abstract

Continuous infusion of cefotaxime, as opposed to intermittent infusion, seems to be advantageous for a number of reasons. However, few data exist on pharmacokinetics of cefotaxime and its metabolite in infants and children. As part of a quality assessment program, concentrations of cefotaxime and its metabolite desacetyl-cefotaxime were examined. Infants and children (age 0-17 years) routinely received cefotaxime by continuous intravenous infusion and had blood samples taken on days 1, 3, and 5 after start of therapy. Measurements were performed by high-performance liquid chromatography (HPLC) of cefotaxime and desacetyl-cefotaxime. Patients receiving a dosage of 100 mg/kg/day had a mean cefotaxime concentration of 24.9 mg/l on day 1, ranging from 0.6 to 182.6 mg/l (N = 222). Cefotaxime concentrations in infants younger than 1 week of age showed the largest variation and significantly decreased on consecutive days (p < 0.001, N = 17), together with a significant drop in the cefotaxime-desacetyl-cefotaxime (cef-des) ratio (p = 0.003, N = 16). Cefotaxime clearance increased significantly during the first days after birth (p = 0.024, N = 16). Patients older than 1 week showed negative and significant correlations of cefotaxime concentrations with calculated glomerular filtration rates (p < 0.0001, N = 73), with no significant change in the cef- des ratio on consecutive days. Overall, cefotaxime concentrations varied widely between patients, in particular in those younger than 1 week. Our data suggest that liver metabolism as well as renal excretion contribute to total body clearance of cefotaxime and increase during the first few days of live.