Basic and clinical studies of cefotiam in neonates and premature infants

The effect of cefotiam (CTM) on neonates and premature infants was examined in basic and clinical studies. Minimum inhibitory concentrations of CTM against 190 clinically isolated strains kept by this department were investigated. This drug was found to have a strong antibacterial effect against Escherichia coli, Klebsiella spp., Proteus mirabilis and Streptococcus agalactiae, Staphylococcus aureus and Staphylococcus epidermidis, although some strains were resistant. The CTM was given to 0–3, 4–7, and ⪴8 day-old premature infants and neonates by intravenous injection at the dose of 20 mg/kg, and we studied changes in serum CTM levels over time. Mean serum CTM levels were 62.3 µg/ml at 15 minutes and 16.4 µg/ml at 6 hours after the injection, with the half-life of 3.6 hours, for the 0–3 day-old premature infants. They were 38.5 µg/ml at 15 minutes and 10.1 µg/ml at 6 hours, with the half-life of 2.9 hours, for the 0–3 day-old neonates. Those levels were 22.5 µg/ml at 15 minutes and 2.9 µg/ml at 6 hours, with the half-life of 1.9 hours, for the 4–7 day-old neonates, and 51.8 µg/ml at 15 minutes and 1.0 µg/ml at 6 hours, with the half-life of 1.1 hours, for the ⪴8 day-old neonates. The CTM was given to 0–3 and ⪴8 day-old premature infants and neonates by 1-hour intravenous drip infusion at the dose of 20 mg/kg, and changes in serum CTM levels after the infusion were followed. The 0–3 day-old premature infant (there was only one subject) had a peak serum CTM level of 21.0 µg/ml 1 hour after the start of the infusion (that is, at the time of its completion), with the level decreased to 8.6 µg/ml at 7 hours and the half-life was 5.4 hours. The mean peak serum CTM level in 0–3 day-old neonates were 36.7 µg/ml at 1 hour, which decreased to a mean of 7.0 µg/ml at 7 hours; the half-life was 2.3 hours. The ⪴8 day-old neonate (1 subject) had 2 peaks of serum CTM levels, 28.4 µg/ml at 30 minutes, deceasing to 21.7 µg/ml at 1 hour, then increasing again to 23.7 µg/ml at 2 hours, and decreasing to 1.9 µg/ml at 7 hours, with the half-life of 1.7 hours after the completion of the infusion. Rates of CTM excretion into the urine of these premature infants and neonates after the injection were examined. Although there were some differences in rates of CTM excretion with different day-ages, excretion rates at 6 hours after the end of the administration were about 10–20% for the 0–3 day-old group and about 40–50% for the ⪴4 day-old group. The CTM was given to 21 neonates and premature infants with bacterial infections. Clinical results were good or excellent in 20 of the 21 patients, and the efficacy rate was 95%. The bacteriological effect of CTM was studied in patients with infection caused by one of 6 strains (2 strains of S. aureus, 2 of S. epidermidis, and 2 of E. coli). Five of the 6 strains were eradicated (the exception was S. aureus), so the efficacy rate was 83%. Side effects of CTM were studied in 27 patients treated. Although no serious side effect was observed, diarrhea occurred in 1 patient, eosinophilia in 1, an elevated GOT level in 2 patients, elevated GOT and GPT level in 1 patient, and the protein induced by vitamin K absence or antagonist (PIVKA II) became detectable in 1 patient.