Abstract
Fundamental and clinical investigations of cefotaxime were carried out in neonates. The following results were obtained.
1. Seven neonates with serious infections caused by identifiable pathogens, including Group B streptococcal meningitis and Group A streptococcal sepsis, were treated by intravenous bolus injection of 20-200mg/kg of cefotaxime 2 or 3 times daily (60-400mg/kg/day). The clinical efficacy of cefotaxime was assessed to be good in 6 patients and fair in 1 patient. Bacteriological efficacy was evaluable in 4 patients, all of whom displayed complete eradication of pathogens.
2. Among 22 neonates administered cefotaxime, adverse reactions appeared in 3 patients. Adverse reactions consisted of a transient skin rash in 1 patientand elevation of GOT in 2 patients.
3. Serum concentrations of cefotaxime and desacetyl cefotaxime were investigated in 8 mature infants and 5 immature infants on days 0-7postpartum.A single intravenous injection of 20 mg/kg produced peak serum concentrations of 31.8-49.7mcg/ml, associated with a half-life of 1.38-4.47 hours, in mature infants and peak serum concentrations of 35.5-55.0 mcg/ml, associated with a half-life of 3.22-6.43 hours, in immature infants. On days 0-2postpartum the half-life was longer than on subsequent days. This tendency was particularly remarkable in immature infants.Serum concentrations of desacetyl cefotaxime displayed high individual variations; no consistent trends were noted.
4. Cefotaxime and desacetyl cefotaxime serum concentrations were studied in 3 neonates undergoing exchanged transfusion (exchanged volume 177 ti 180ml/kg) on 1-4 days postpartum.Serum concentrations of cefotaxime after exchanged transfusion were equivalent to 32.6-63.9% of the pretransfusion level, while those of desacetyl cefotaxime were 75.2-106% of the pretransfusion level.
5. Minimal inhibitory concentration (MICs) and minimal bactericidal concentration (MBCs) of cefotaxime were determined against clinical isolates.MICs for inoculum sizes of 108/ml and 106/ml were respectively 3.13-25mcg/ml and 3.13-25mcg/ml against S.aureus, 0.024mcg/ml and 0.012mcg/ml against Group A Streptococcus, 0.05 mcg/ml and 0.05mcg/ml against Group B Streptococcus and 0.39mcg/ml and 0.1mcg/ml against E. coli.MBCs for an inoculum size of 108/ml were 3.13-100mcg/ml or over against S. aureus, 0.012mcg/ml against GroupA Streptococcus, 0.39mcg/ml against Group B Streptococcus and 1.56mcg/ml against E. coli.
