Electronic Health Records and Pharmacokinetic Modeling to Assess the Relationship between Ampicillin Exposure and Seizure Risk in Neonates.

Abstract

OBJECTIVE:

To evaluate the relationship between ampicillin dosing, exposure, and seizures.

STUDY DESIGN:

This was a retrospective observational cohort study of electronic health record (EHR) data combined with pharmacokinetic model derived drug exposure predictions. We used the EHR from 348 Pediatrix Medical Group neonatal intensive care units from 1997 to 2012. We included all infants 24-41 weeks gestational age, 500-5400 g birth weight, first exposed to ampicillin prior to 25 days postnatal age. Using a 1-compartment pharmacokinetic model and EHR data, we simulated maximum ampicillin concentration at steady state (Cmaxss, µg/mL) and area under the concentration time curve from 0 to 24 hours (AUC24, µg*h/dL). Using multivariable logistic regression, we evaluated association between ampicillin dosing, exposure, and seizures as documented in the EHR.

RESULTS:

We identified 131 723 infants receiving 134 041 courses of ampicillin for 653 506 infant-days of exposure. The median daily dose was 200 mg/kg/d (25th, 75th percentile; 100, 200). Median Cmaxss and AUC24 were 256.6 µg/mL (164.3, 291.5) and 2593 µg*h/dL (1917, 3334). On multivariable analysis, dosing was not associated with seizures. However increasing Cmaxss (OR = 1.10, 95% CI 1.03, 1.17) and AUC24 (OR 1.11, 95% CI 1.05, 1.18) were associated with increased odds of seizures.

CONCLUSIONS:

In this cohort of hospitalized infants, higher ampicillin exposure was associated with seizures as documented in the EHR.

• Authors: Christoph P Hornik, Daniel K Benjamin Jr, P Brian Smith, Michael J Pencina, Adriana H Tremoulet, Edmund V Capparelli, Jessica E Ericson, Reese H Clark, Michael Cohen-Wolkowiez, Best Pharmaceuticals for Children Act—Pediatric Trials Network
• Journal: The Journal of pediatrics (J Pediatr) Vol. 178 Pg. 125-129.e1 (Nov 2016) ISSN: 1097-6833 [Electronic] United States
• PMID: 27522443 (Publication Type: Journal Article, Observational Study)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• Ampicillin

Topics

• Ampicillin (administration & dosage, adverse effects, pharmacokinetics)
• Anti-Bacterial Agents (administration & dosage, adverse effects, pharmacokinetics)
• Area Under Curve
• Cohort Studies
• Electronic Health Records
• Female
• Humans
• Infant
• Infant, Newborn
• Intensive Care Units, Neonatal
• Logistic Models
• Male
• Models, Biological
• Retrospective Studies
• Risk Assessment
• Seizures (chemically induced, epidemiology)