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Pharmacokinetics and plasma bactericidal activity of aztreonam in low-birth-weight infants
Insights
Aztreonam dosing was evaluated in low-birth-weight infants. Pharmacokinetics were similar between initial and steady-state doses, with effective bactericidal titers observed.
Area of Science:
- Pharmacology
- Neonatal Medicine
- Infectious Diseases
Background:
- Low-birth-weight infants often require antibiotic therapy.
- Understanding aztreonam pharmacokinetics is crucial for effective treatment in neonates.
- Limited pharmacokinetic data exists for aztreonam in this vulnerable population.
Purpose of the Study:
- To characterize the pharmacokinetics and bactericidal activity of aztreonam in low-birth-weight infants.
- To assess the impact of dosing frequency on aztreonam plasma concentrations.
- To evaluate the relationship between birth weight and aztreonam pharmacokinetics.
Main Methods:
- Intravenous aztreonam administered to 26 low-birth-weight infants ( < 2,000 g).
- Dosing adjusted: every 12 h (week 1), then every 8 h (weeks 2-4).
- Plasma concentrations, pharmacokinetic models (one-compartment, noncompartment), and bactericidal titers (vs. E. coli, P. aeruginosa) were measured.
Main Results:
- Aztreonam pharmacokinetics were well-described by both models, with similar values on day 1 and steady-state.
- Mean peak plasma concentrations ranged from 65-83 µg/ml, higher in larger infants.
- Half-lives (5.4-8.6 h) were consistent across birth weights. Effective peak and trough bactericidal titers were achieved.
- Urinary concentrations on day 1 ranged from 24-460.7 µg/ml.
Conclusions:
- Aztreonam exhibits predictable pharmacokinetics in low-birth-weight infants.
- The established dosing regimen achieved therapeutic concentrations and bactericidal activity.
- Aztreonam is a viable treatment option for infections in this population, with dosing adjustments potentially guided by weight.
Abstract:
Aztreonam (30 mg/kg) was administered intravenously every 12 h during week 1 and every 8 h during weeks 2 to 4 of life to 26 low-birth-weight (less than 2,000 g) infants, and plasma concentration-time curves were measured on two occasions. The pharmacokinetics were described equally well by one-compartment and noncompartment models, and the values on day 1 were similar to those measured during the steady state on days 3 to 6. The mean peak plasma concentrations at completion of the 10-min infusion were from 65 to 83 micrograms/ml, the higher concentrations being seen in the larger infants. The half-lives of aztreonam ranged from 5.4 to 8.6 h and did not change significantly with birth weight. The median peak and trough plasma bactericidal titer against a strain of Escherichia coli (MBC, 10 micrograms/ml) was 1:16. Against a strain of Pseudomonas aeruginosa (MBC, 16 micrograms/ml), the median peak and trough bactericidal titers were 1:8 to 1:16 and 1:4, respectively. The urinary concentrations of aztreonam on day 1 of therapy were from 24 to 460.7 micrograms/ml (mean +/- 1 standard deviation, 254 +/- 113 micrograms/ml).