Fundamental and clinical evaluations of ceftazidime in neonates

Abstract

Ceftazidime (CAZ) intravenous injection was evaluated from fundamental and clinical aspects in neonates, and the results obtained are summarized below. Following a 60-minute intravenous drip infusion of CAZ at 10 mg/kg, the peak serum level was 19.8 micrograms/ml at 30 minutes after the completion of the infusion(half-life: 2.75 hours). Following 30 to 60-minute intravenous drip infusions of CAZ at 20 mg/kg, the mean peak serum levels of CAZ were 33.1-33.0 micrograms/ml. Mean levels at 6 hours were 5.2-6.7 micrograms/ml (half-life: 1.6-4.1 hours). Following 30 to 60-minute intravenous drip infusions of CAZ at 25-30 mg/kg, peak serum levels were 51.7-64.6 micrograms/ml (half-life: 1.6-2.05 hours). Dose response relationship was clearly observed in peak serum levels after intravenous drip infusion, and half-lives of serum CAZ levels in neonates aged 0-10 days tended to be longer than those in infants. Following intravenous administration of CAZ at 20-30 mg/kg, urinary excretion rates during the first 6 hours were 18.7-66.5%, and the rates were low in neonates compared to those in infants and children. Following a 60-minute intravenous drip infusion of CAZ at 28.7 mg/kg, the cerebrospinal fluid level was 5.0 micrograms/ml at 3 hours, the ratio of cerebrospinal fluid level to serum level was 22.5%. Eleven neonates were subjected to the present study. Clinical efficacy of CAZ was excellent in sepsis caused by A. anitratus, which showed higher sensitivity to CAZ compared with other cephem antibiotics of the third generation. In all of the other cases, including those of pertussis and acute urinary tract infections and in the prophylaxis of amniotic infection, clinical efficacy of CAZ was excellent or good. S. epidermidis, E. coli and A. anitratus, identified from cultures of pharynx, urine or blood, were rapidly eliminated during the CAZ treatment. Doses of CAZ used in the present study were 29-133 mg/kg/day, mostly in the range of 40-60 mg/kg/day. Durations of treatment ranged from 3 to 10 days. Neither systemic nor local adverse effect was observed, nor was any abnormality observed in laboratory findings.