[Pharmacokinetic, bacteriological and clinical studies on imipenem/cilastatin sodium in neonates].

Pharmacokinetic, bacteriological and clinical studies on imipenem/cilastatin sodium (IPM/CS) were performed in neonates. The results obtained are summarized as follows. 1. Plasma levels and urinary excretion of IPM and CS sodium were determined in 7 neonates with ages between 7 and 26 days (gestation periods were 37 to 41 weeks and birth weights were 2,410 to 3,890 g) upon 1 hour drip intravenous infusion of IPM/CS at 10 mg/10 mg/kg, or 20 mg/20 mg/kg. Mean plasma concentrations of IPM reached their peaks at the end of infusion with levels of 12.7 +/- 3.0 micrograms/ml for the group given 10 mg/10 mg/kg, and 19.1 +/- 4.1 micrograms/ml for 20 mg/20 mg/kg. The concentration of IPM in plasma showed a dose-response to the 10 mg/10 mg/kg and 20 mg/20 mg/kg dosages. Concentrations decreased with half-lives of 1.87 +/- 0.71 hours and 1.97 +/- 0.21 hours for the low and the high dosages, and plasma levels at 8 hours after administration were 0.3 +/- 0.1 microgram/ml and 0.8 +/- 0.3 microgram/ml, respectively. Mean urinary recovery rates in 8 hours after administration were 37.6 +/- 11.8% and 26.8 +/- 17.2% for the low and the high dosages. While, mean plasma concentrations and mean urinary recovery rates of CS were higher than those of IPM, mean plasma half-lives of CS were similar to IPM. 2. IPM/CS was administered to 11 neonatal patients (with ages between 1 and 26 days) of various bacterial infections, and clinical effectiveness, bacteriological efficacy and adverse reactions were evaluated. Clinical efficacies in cases including 7 with acute pneumonia and 1 each with suspected septicemia, intrauterine infection, acute urinary tract infection and periproctal abscess were judged excellent in 10 and good in 1 case, and the efficacy rate was 100%. Causative organisms isolated from these patients included 3 strains of Escherichia coli and 1 strain each of Streptococcus pyogenes, Streptococcus agalactiae Enterococcus faecalis and Haemophilus influenzae. All the organisms were eradicated by IPM/CS, thus the bacteriological eradication rate was 100%. No adverse reactions were observed, but decreased platelet in 1 patient and increased GOT in 2 patients were found as abnormal laboratory test values. These changes, however were transient, and returned to normal after discontinuation of IPM/CS. It was concluded that the clinical results of IPM/CS are indicative of excellent efficacy, safety and usefulness of the drug in the treatment of infections in neonates.