Ampicillin Dose for Early and Late-Onset Group B Streptococcal Disease in Neonates

Ampicillin is frequently used in neonates for early- and late-onset group B streptococcal (GBS) disease. In 2019, the American Academy of Pediatrics (AAP) published guidelines for GBS which included updated dosing recommendations for ampicillin for bacteremia and provided specific dosing recommendations for meningitis. The dosing recommendations in the guidelines were based off the 2018 Report of the Committee on Infectious Diseases (i.e., Red Book), which differed from the 2015 Red Book. For bacteremia, no dosing changes were recommended for ampicillin dosing in neonates ≤ 7 days of postnatal age (PNA), but less frequent dosing intervals were recommended for neonates > 7 days PNA. For meningitis, increased dosing recommendations were provided in the update. However, the rationale and supporting evidence for these changes were not provided. A literature search was performed to review articles pertaining to the pharmacokinetics (PK), pharmacodynamics (PD) and safety of ampicillin in neonates. The ampicillin dosing recommendations in the AAP guidelines were mainly supported by a 2014 publication that evaluated the PK and PD of ampicillin in neonates with gestational age (GA) of 24 to 41 weeks and PNA of 0 to 25 days. The proposed dosing from this study for bacteremia is included in the 2018 Red Book and 2019 guidelines. For meningitis, no supporting evidence was identified for the dosing recommendations in the 2018 Red Book and 2019 guidelines. Only one study has evaluated ampicillin concentrations in cerebrospinal fluid, but proposed dosing from this study was much lower than that included in the guidelines. The high ampicillin doses for GBS meningitis should be used with caution, as high ampicillin concentrations have been associated with seizures and no studies have evaluated efficacy of this dosing strategy. The purpose of this review is to identify key pieces of literature regarding dosing recommendations and safety of ampicillin in neonates. KEY POINTS: · Recent guidelines provide dosing recommendations for ampicillin, but the supporting evidence is not included.. · Literature supporting evidence for ampicillin dosing for bacteremia is available, but not for dosing for meningitis.. · Recommended meningitis dose may result in supratherapeutic concentrations and increase seizure risk..