Cefotaxime pharmacokinetics and treatment of meningitis in neonates.

Pharmacokinetic studies on cefotaxime/desacetylcefotaxime were carried out in very low birth weight newborns (n = 18; 500-1500 g; 28.4 +/- 2.4 weeks gestational age) during the first week of life. We have previously reported that the elimination t 1/2 of cefotaxime (3.4-6.4 h) and desacetylcefotaxime (9.4 h) was longer than previously described in term infants and children. In very low birth weight neonates, a single 50 mg/kg daily dose of cefotaxime may produce accumulation of the metabolite desacetylcefotaxime in serum. In a non-comparative prospective clinical trail, 22 infants (one week - three months) were treated for gram-negative enteric bacillary meningitis with cefotaxime at a dosage of 50 mg/kg/day. The predominant pathogen was Escherichia coli in 14 cases and Enterobacter cloacae in four cases. Cultures of the cerebrospinal fluid obtained 24-48 h after the initiation of treatment were sterile in all subjects. Survival and complication rates of 95% and 19%, respectively, were observed. This compared favorably to previously published experiences with alternative treatment regimens for neonatal gram-negative enteric meningitis. In both the pharmacokinetic and meningitis studies, the safety profile for cefotaxime was excellent with no adverse reactions.