PHARMACOKINETIC AND CLINICAL EVALUATIONS OF AZTREONAM MONOTHERAPY AND AZTREONAM AND AMPICILLIN COMBINATION THERAPY IN NEONATES AND PREMATURE INFANTS

Abstract

One-shot intravenous injection of aztreonam (AZT), a monobactam-class β-lactam antibiotic, 20 mg/kg was administered to 4 neonates and 2 premature infants, a total of 6 cases, and plasma and urinary concentrations and urinary recovery rates were determined. Also, one-shot intravenous injection averaging 70.9 mg/kg/day of AZT alone was given to 0- to 43-day neonates and premature infants in b.i.d. to q.i.d. for an average of 8 days for the treatment (6 cases) and prophylaxis (11 cases) of infections. Furthermore, a combination therapy of AZT and ampicillin (ABPC) was applied to 0- to 79-day neonates and premature infants for the treatment (28 cases) and prophylaxis (18 cases) of infections. Average daily dosage of AZT 46.6 mg/kg was given by one-shot intravenous injection or by drip infusion in b.i.d. or t.i.d. for an average of 8 days. Average daily dosage of ABPC 78.6 mg/kg was given in the same daily frequency, route and average duration as AZT. Thus, clinical effects, prophylactic effects against infection, bacteriological effects as well as side effects and clinical laboratory test values were studied with the following results.
1. When AZT 20 mg/kg was administerd to 1 case each of 6- and 7-day neonates by oneshot intravenous injection, the plasma concentrations were the highest at 5 minutes after the administration in both cases. Specifically, they were 62.9 and 72.7 μg/ml with AUCs of 216.6 and 231.6 μg·hr/ml and half-lives of 2.80 and 2.97 hours, respectively. When AZT 20 mg/kg was administered to 5- and 6-day premature infants by one-shot intravenous injection, the plasma concentrations were the highest at 15 minutes after administration in the former and 5 minutes in the latter, at va·hr/ml, respectively, and larger than AUCs of the above-mentioned neonates. Half-lives were 5.74 and 4.87 hours, respectively and longer than those of the above-mentioned neonates. When AZT 20 mg/kg was administered to 8- and 13-day neonates by one-shot intravenous injection, the plasma concentrations were the highest at 30 minutes after administration in the former and 5 minutes in the latter, at values of 43.4 and 76.9 μg/ml, respectively. AUCs were 202.9 and 189.8 μg·hr/ml, respectively, and they were smaller than those of the above-mentioned neonates and premature infants. Half-lives were 3.11 and 2.00 hours and they were similar to or longer than those of the 6- and 7-day neonates.
2. Urinary concentrations were determined in the same cases as the determination of the plasma concentrations. The concentration was the highest in urine samples collected during 0 to 2 hours or 2 to 4 hours after administration showing values ranging 338 to 1,053 μg/ml and 48.6 to 75.3% of the administered drug was recovered in the first 8 hours in 5 out of 6 cases and in 6 hours in remaining 1 case after the administration. These recovery rates did not indicate significant differences in different day-ages determined.
3. Clinical effects of AZT against bacterial infections in the monotherapy were “excellent”for 2 of 6 cases and “good” for 3 and “good”; for the remaining 1 case. AZT showed prophylactic effect in every one of the 11 cases in which AZT administration was intended for the prophylaxis of infections. Meanwhile, clinical effects of AZT and ABPC in combination against bacterial infections were “good” for 25 cases, “fair” for 2 cases and “poor” for 1 case and the efficacy rate was 89.3%. In every case of the 18 cases in which administration of the drugs were intended for the prophylaxis of infections, the drug combination was prophylactically effective.
4. Bacteriological effects of AZT in the monotherapy were determined against 2 strains of Escherichia coli and a mixed infection of E. coli and Klebsiella pneumoniae and it was found that these bacteria were eradicated.