PHARMACOKINETICS AND CLINICAL STUDIES ON AZTREONAM IN NEONATES AND PREMATURE INFANTS (THE SECOND REPORT)

Pharmacokinetics and clinical effects were studied in a combination therapy with aztreonam (AZT) and ampicillin (ABPC) in neonates and premature infants. The results obtained are summarized as follows.<BR>1. Pharmacokinetics<BR>(1) Average serum concentrations at 30 minutes after one-shot intravenous injection of AZT 20 mg/kg and ABPC 25 mg/kg to a 4-7 days age-group of neonates were 41.3 (AZT) and 30.5 (ABPC) μg/ml, respectively. They gradually decreased to 14.7 and 2.7 μg/ml at 6 hours after the administration, but the concentration of AZT was always higher than that of ABPC.<BR>(2) Serum half-lives (T 1/2) in the 4-7 days age-group were 3.61 hours for AZT and 1.42 hours for ABPC, thus T 1/2 of AZT was longer. However, T 1/2 of AZT was scarcely affected in the concomitant administration of ABPC.<BR>(3) Urinary excretion of AZT in the concomitant administration to the 4-7 days age-group was 52.7%, which was the same or a little higher comparing to that in AZT alone administration.<BR>2. Clinical studies<BR>(1) AZT and ABPC were concomitantly administered to 160 cases and 133 cases were evaluated for efficacy. Pathogenic organisms were identified in 29 cases (Group A) and the efficacy rate was 86.2% (25/29). The number of cases in which pathogenic organisms were not identified (Group B) was 50 and in this group, the efficacy rate was excellent, 94.0% (47/50). AZT and ABPC were concomitantly administered to 54 cases for prophylaxis and in all the cases the administrations showed prophylactic effect.<BR>(2) Bacterial changes were confirmed in 21 of the 29 cases in which pathogenic organisms were identified initially and all of these 21 cases showed bacterial eradication, i.e., the bacterial eradication rate in the treatment was 100%.<BR>(3) There were 2 cases in which side-effects were observed among the analyzed 152 cases (1.3%). The side effects found were 1 case each of diarrhea and eruption. Abnormal laboratory values were found in 23 cases (15.9%), i.e., eosinophilia (9 cases), platelet-increase (4), elevation of GOT (4), elevation of GOT and GPT (3) and others (3).<BR>From the above pharmacokinetics and clinical results, the combination therapy of AZT and ABPC is considered to be one of the useful empiric antibiotic-therapies when pathogenic organisms are unknown in the infections of neonates and premature infants.