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Greater ampicillin exposure linked to seizures in hospitalized children
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Heavier doses of ampicillin use in hospitalized infants were associated with seizures, according to data published in Pediatrics.
“Our study linked predicted ampicillin exposure with safety events in infants by combining [electronic health record (EHR)] data with predicted ampicillin exposures from a [pharmacokinetic (PK)] model,” Christoph P. Hornik, MD, MPH, pediatric cardiologist and critical care medicine specialist at Duke Clinical Research Institute, and colleagues wrote. “We found that higher ampicillin exposure was associated with increased odds of seizures, but ampicillin dosing alone was not. These findings suggest that lowering exposure, not just dosing, is necessary to improve the drug’s safety profile.”
In their retrospective, observational analysis, Hornik and colleagues simulated ampicillin exposures from EHR data and a population PK model derived from an infant cohort drawn from 348 neonatal ICUs and enrolled in a separate PK study from 1997 to 2012. The cohort included infants born between 24 and 41 weeks’ gestation who weighed 500 g to 5,400 g at birth and were exposed to ampicillin before age 25 days.
Analysis showed that 131,723 infants received 134,041 doses of ampicillin across 653,506 infant-days of exposure. No associations were observed between ampicillin use and seizures in the median daily dose (200 mg/kg per infant-day). Greater doses of ampicillin, however, were linked to an increase in seizures when the researchers simulated maximum ampicillin concentration at a steady state (OR = 1.1; 95% CI, 1.03-1.17) and area under the concentration time curve from 0 to 24 hours (OR = 1.11; 95% CI, 1.05-1.18) upon multivariable analysis.
“Reliance on age-based dosing recommendations alone may be insufficient to avoid this rare, but serious adverse event, such as seizures,” the researchers said. “Newer dosing recommendations may provide more predictable ampicillin exposure. Until this has been proven in future studies, clinical vigilance and dose adjustment are necessary to improve ampicillin’s safety profile.” – by Kate Sherrer
Disclosure: Hornik reports receiving salary support for research from the National Center for Advancing Translational Sciences of the NIH. Please see the full study for a list of all other authors’ relevant financial disclosures.
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