[Fundamental and clinical investigations of cefotaxime in neonates]

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 20-200 mg/kg of cefotaxime 2 or 3 times daily (60-400 mg/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 patient and 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 0-7 postpartum. A single intravenous injection of 20 mg/kg produced peak serum concentrations of 31.8-49.7 mcg/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 0-2 postpartum 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 177-180 ml/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 10(8)/ml and 10(6)/ml were respectively 3.13-25 mcg/ml and 3.13-25 mcg/ml against S. aureus, 0.024 mcg/ml and 0.012 mcg/ml against Group A Streptococcus, 0.05 mcg/ml and 0.05 mcg/ml against Group B Streptococcus and 0.39 mcg/ml and 0.1 mcg/ml against E. coli. MBCs for an inoculum size of 10(6)/ml were 3.13-100 mcg/ml or over against S. aureus, 0.012 mcg/ml against Group A Streptococcus, 0.39 mcg/ml against Group B Streptococcus and 1.56 mcg/ml against E. coli.