1547. Modeling Pharmacokinetics and Pharmacodynamics of Meropenem Utilizing a Novel Infusion Method of Bolus to Prolonged Infusion

Abstract Background Dose optimization of antibiotics has been shown to increase the likelihood of achieving pharmacodynamic efficacy targets and improve clinical outcomes. For carbapenems, achieving greater than 40% time above minimum inhibitory concentration (T>MIC) has been shown to be correlated with clinical efficacy. Increasing bacterial resistance and rising MICs makes it more difficult for clinicians to rely on traditional dosing strategies to meet pharmacodynamic goals. Further optimization methods beyond extended infusion may be necessary to achieve certain pharmacodynamics goals. Methods We performed a Monte Carlo simulation investigating a novel method of meropenem administration, bolus to prolonged infusion (BPI). Multiple meropenem dosing regimens utilizing BPI were evaluated over 5000 patients utilizing pharmacokinetic profiles from 30 total patients. Patients were studied in 3 separate groups: <120 kg, ≥120 kg/non-critically ill and ≥120 kg/critically-ill. Bolus doses varied from 250–1000 mg and were paired with infusion doses varying from 500–1500 mg. Bolus plus infusion time totaled 3 hours and each dose was modeled with an 8-hour interval for both first dose and at steady state; BPI dosing was utilized for each dose. The primary outcome was probability of target attainment (PTA) of 40% time above minimum inhibitory concentration (T>MIC). Secondary outcomes included PTA 54% T>MIC and PTA 100% T>MIC. Results All doses studied achieved > 90% PTA of 40% T>MIC for MICs of ≤8 μg/mL at both first dose and steady state in the <120 kg and ≥120 kg/non-critically ill patient groups. In the ≥120 kg/critically ill patient group, all doses achieved > 90% PTA of 40% T>MIC for MICs of ≤4 μg/mL. Conclusion BPI achieves high probability of target attainment at nonresistant MICs for Pseudomonas aeruginosa and enteric Gram-negative organisms across the 3 patient groups studied. Disclosures All authors: No reported disclosures.