A pharmacokinetic and clinical evaluation of ceftazidime in neonates and premature infants. A study of ceftazidime in the perinatal co-research group

Abstract

Ceftazidime (CAZ) was evaluated for its pharmacokinetics and clinical usefulness in neonates and premature infants. The results obtained were summarized below. Following intravenous injection of CAZ 10 or 20 mg/kg to neonates and premature infants, dose response was observed in serum concentrations ranging from 5.1 to 21.9 micrograms/ml at 6 hours after the injection. The serum half-life tended to be longer in premature infants than in neonates; the half-life being longer for an infant with lower day-age. Urinary recovery rates during the first 6 hours after single administrations of 10 mg/kg of CAZ tended to be higher in neonates than in premature infants, and higher rates were observed in older infants. However, no noticeable difference was observed after the administration of CAZ 20 mg/kg. Clinical efficacy was evaluated in 99 neonates and 55 premature infants (156 infections), daily doses ranging from 21.1 to 246.4 mg/kg. Out of 105 cases of common infections, mainly 44 cases with causative organisms identified (including 17 of sepsis, 7 of pneumonia, 4 of purulent meningitis, 11 of urinary tract infections) were examined for the clinical efficacy. The efficacy of CAZ was excellent in 21, good in 18, fair in 1 and poor in 4, with the efficacy rate of 88.6%. In the remaining 61 cases, i.e., 37 with causative organisms unknown and 24 with signs of intrauterine infections, the efficacy rate was 95.1%. Other than these cases, additional 51 cases were given CAZ solely for prophylaxis of infections, and the results were found satisfactory. On the whole, clinical efficacy rate of CAZ was 94.9% in 156 cases. Out of the 44 cases examined for bacteriological responses, 38 were evaluated as 'eradicated', 3 'persisted' and 3 'unknown' with eradication rate of 92.7%. Replacement of organisms (superinfection) was observed in 3 cases. Out of 179 cases in which adverse effects were assessable, adverse effects were observed in a total of 4 cases (2.2%), i.e., 3 cases of diarrhea (1.7%) and 1 case of rash (0.6%), and abnormal laboratory findings were observed in a total of 14 cases (7.8%), i.e., increase in eosinophiles count in 8 (4.5%), elevation of GOT in 3 (1.7%), increase in platelet, elevation of GOT . GPT, and elevation of GOT . GPT . BUN in 1 case each (0.6%). None of them were severe and they were transient. Elevations of bilirubin and cases of positive PIVKA II associated with CAZ were not observed.(ABSTRACT TRUNCATED AT 400 WORDS)