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[Fundamental and clinical evaluations of ceftazidime in neonates and premature infants]
Insights
Ceftazidime (CAZ) pharmacokinetics in neonates and infants show longer plasma half-lives and higher AUC values in younger infants, indicating age-dependent drug exposure. Dosing adjustments may be necessary for optimal therapeutic effects in this population.
Area of Science:
- Pharmacokinetics and Pharmacodynamics
- Pediatric Pharmacology
- Infectious Diseases
Context:
- Ceftazidime (CAZ) is a crucial antibiotic for treating bacterial infections in vulnerable pediatric populations.
- Understanding the pharmacokinetic profile of CAZ in neonates and infants is essential for safe and effective therapeutic use.
- Age-related differences in drug metabolism and elimination can significantly impact antibiotic efficacy and safety in early life.
Purpose:
- To determine the plasma concentration, urinary concentration, and urinary recovery rate of ceftazidime (CAZ) in neonates and premature infants.
- To evaluate the clinical efficacy, prophylactic effects, and bacteriological response to CAZ in infants.
- To assess the adverse effects and laboratory findings associated with CAZ administration in pediatric patients.
Summary:
- Ceftazidime (CAZ) pharmacokinetics were studied in 24 neonates and premature infants (0-31 days) at 10 mg/kg or 20 mg/kg IV doses.
- Higher AUC values and longer plasma half-lives were observed in younger infants, with dose-dependent responses noted.
- Clinical efficacy, prophylactic effects, and adverse events were evaluated in a larger cohort of 43 infants (0 days to 1 year 9 months).
Impact:
- Provides critical pharmacokinetic data for optimizing ceftazidime dosing in neonates and infants.
- Informs clinical decision-making regarding the use of ceftazidime for treating and preventing infections in pediatric patients.
- Highlights the importance of age-specific dosing strategies to ensure therapeutic success and minimize potential adverse events.
Abstract:
Ceftazidime (CAZ) was administered to 24 neonates and premature infants aged 0-31 days in a dose of 10 mg/kg or 20 mg/kg by an intravenous bolus injection, and plasma concentration, urinary concentration and urinary recovery rate during the first 6 hours after the administration were determined. The CAZ was also administered to a total of 43 patients consisting of neonates, premature infants and infants at ages ranging from 0 day to 1 year 9 months (21 suffering or suspectedly suffering with various bacterial infections, and 22 treated for prophylaxis of infections), by intravenous bolus injections in a mean daily dose of 59.6 mg/kg in 2 to 4 divided doses for 9 days on the average. The clinical efficacy, prophylactic effects and bacteriological response were evaluated. Adverse effects of the drug were examined in 65 cases including 22 drop-out cases, and in some of them, abnormal laboratory findings were also examined. The results obtained are summarized as follows: Patients given 10 mg/kg of CAZ were divided into 5 groups on the basis of age: 0-3 days, 4-7 days, 8-14 days, 15-21 days, and 29 days and older, and mean peak plasma concentrations of CAZ were 40.7, 43.1, 37.1, 38.0 and 35.6 micrograms/ml, respectively, at 5 minutes after administration, with no significant difference. Mean AUC values were higher in younger-age groups, i.e. 189.9, 170.8, 159.1, 135.3 and 134.4 micrograms X hr/ml for the 5 different day-age groups, respectively, and mean half-lives of CAZ in plasma tended to be longer in younger-age groups, i.e. 3.16, 3.05, 2.84, 2.44 and 2.43 hours for the 5 groups, respectively. Patients given 20 mg/kg of CAZ were divided into 4 groups also on the basis of age: 0-3 days, 4-7 days, 8-14 days, and 15-21 days, and mean peak plasma concentrations for the 4 day-age groups were 72.9, 73.3, 70.0 and 78.4 micrograms/ml, respectively, at 5 minutes after administration, without any difference among these groups. Mean AUC values were 429.9, 327.3, 279.3 and 302.1 micrograms X hr/ml for the 4 groups, respectively, with the highest AUC in the youngest-age group. Dose response was observed in mean peak plasma concentrations and mean AUCs when 10 mg/kg and 20 mg/kg dose groups were compared for similar day-age patients. Mean half-lives of CAZ in plasma were 4.01, 3.51, 3.00 and 3.07 hours, the longest being in the youngest-age group.(ABSTRACT TRUNCATED AT 400 WORDS)