Evaluating the duration of post-discontinuation therapeutic ampicillin exposures in preterm infants
Angelique E Boutzoukas1,2, Jennifer Le3, Ryan Kilpatrick4
1Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA. Angelique.boutzoukas@duke.edu.
Insights
Many preterm infants have prolonged therapeutic antibiotic exposures after ampicillin treatment. This extended post-discontinuation antibiotic exposure (PDAE) duration suggests shorter antibiotic courses may be suitable for preterm neonates.
Area of Science:
- Neonatal pharmacology
- Pediatric infectious diseases
- Antibiotic stewardship
Background:
- Empiric ampicillin is commonly used for preterm infants.
- Understanding post-discontinuation antibiotic exposure (PDAE) is crucial for optimizing treatment duration.
- Preterm infants have unique pharmacokinetic profiles that affect drug clearance.
Purpose of the Study:
- To determine the duration of therapeutic PDAE in preterm infants receiving ampicillin.
- To assess the impact of gestational age on PDAE.
- To inform potential adjustments to antibiotic dosing regimens in neonates.
Main Methods:
- Prospective study involving 27 preterm infants (<37 weeks gestational age).
- Collection of 49 post-discontinuation pharmacokinetic samples.
- PK simulations used to predict ampicillin exposure and PDAE duration.
Main Results:
- Therapeutic ampicillin exposure (≥1 μg/mL) persisted for a median of 33 hours post-discontinuation.
- Exposure duration varied significantly with gestational age, longer in extremely preterm infants (<28 weeks GA).
- High probability (95%) of therapeutic exposure at 24 hours, decreasing to 60% at 36 hours.
Conclusions:
- Preterm infants often experience prolonged therapeutic PDAE following ampicillin.
- Gestational age is a key factor influencing PDAE duration.
- Consideration of shorter ampicillin courses may be warranted in preterm neonates to optimize antibiotic stewardship.
Objective:
Determine if preterm infants have prolonged therapeutic post-discontinuation antibiotic exposures (PDAE) following empiric ampicillin.
Study Design:
Prospective study of 27 infants ≤7 days and <37 weeks gestational age (GA) receiving ampicillin (200 mg/kg/day); 49 post-discontinuation PK samples were collected. Exposures were predicted using PK simulations and a prior ampicillin PK model. The probability of target attainment 24- and 36-h after the final ampicillin dose for various minimum inhibitory concentrations (MICs) and the duration of therapeutic PDAE was calculated.
Result:
At 24- and 36-h after ampicillin, the probability of exposures ≥1 μg/mL was 95% and 60%, respectively. PDAE (≥1 μg/mL) lasted a median 33 h (95% confidence interval: 15, 79), and varied with GA, from median 53 h (<28 weeks GA) to 27 h (34-36 weeks GA).
Conclusion:
Many preterm infants experience therapeutic exposures at least 24 h after the final ampicillin dose. Shorter courses could be considered.
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