P-1229. Characterization of Ampicillin (AMP) and Vancomycin (VAN) Pharmacokinetics-Pharmacodynamics (PK-PD) in a Neutropenic Murine Invasive Enterococcal Infection Model
Brian D VanScoy, Allison N Seyfried, Alexander S MacGregor, Micah Nasman, Christopher M Rubino, Rodrigo E Mendes, Helio Sader, Paul G Ambrose, Sujata M Bhavnani
TL;DR
This study characterizes the effectiveness of ampicillin and vancomycin against enterococcal infections in a mouse model, providing new pharmacokinetic-pharmacodynamic targets for treatment decisions.
Contribution
The study provides novel PK-PD targets for ampicillin and vancomycin against Enterococcus species using a newly developed neutropenic murine infection model.
Findings
Ampicillin f %T >MIC targets for bacterial stasis and 1-log reduction were 25.5% and 44.7% for E. faecalis, and 16.5% and 20.3% for E. faecium.
Vancomycin fAUC:MIC ratio targets for these endpoints were 9.61 and 25.5 for E. faecalis, and 6.62 and 18.3 for E. faecium.
The model enabled robust PK-PD characterization of both drugs against enterococcal isolates.
Abstract
AMP and VAN were developed in the 1950s and have remained important therapies for enterococcal infections. Current treatment decisions are based on in vitro susceptibility test interpretive criteria (STIC) using epidemiology data rather than robust PK-PD data due to the poor growth of Enterococcus species in standard pre-clinical infection models. The goal of these studies was to characterize the PK-PD of AMP and VAN against panels of Enterococcus faecalis and E. faecium isolates using a neutropenic murine invasive enterococcal infection model that we developed. Single-dose PK studies were completed in neutropenic mice infected with E. faecalis ATCC 29212. Plasma samples were collected over 7 time points following subcutaneous administration of 4 doses of AMP (4.50, 37.5, 150, and 600 mg/kg) or VAN (0.35, 7.00, 64.0, and 200 mg/kg). 24-hour dose-ranging studies were completed using 5…
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Taxonomy
TopicsAntibiotics Pharmacokinetics and Efficacy · Antimicrobial Resistance in Staphylococcus · Clostridium difficile and Clostridium perfringens research