Pharmacokinetics of cefotaxime in neonates and children: clinical aspects

The chemotherapeutic prerequisites for treating infection in neonates are based on the specific pathogenic spectrum, the immature immunological system and the physiological process of maturation and adaptation. This explains why there is such a large range of attainable antibiotic concentrations. The matter is complicated even more in that the initial blind treatment should be as accurate as possible. There are, however, no major differences between the prerequisites for the treatment of older children and adults. Two examples show that the pharmacokinetic aspects are basically the same for older children and adults. We set 4 to 5 mg/l as the upper limiting value (easily attainable) in our pharmacokinetic study, based on the suspected pathogens causing serious infections in neonates, and on the cefotaxime serum concentrations during the treatment of seven critically ill neonates and premature infants. The computer calculations are based on doses of 100 mg/kg/day given to eight children, divided into either two or three equally spaced dosages. The patients ranged from premature infants (1.2 kg) to a 31½year-old child; the half-lives from 6 h to 28 min. Total clearance was between 0.031 and 0.479 1.kg/h. The volume of distribution ranged from 0.16 1/kg for a patient with renal insufficiency and 0.78 1/kg for a neonate with normal weight. Whereas the dosage is too high in the case of premature infants, there were intervals in the cefotaxime schedule studied where there was no antibiotic detectable in serum concentrations from non-premature infants and older children.