Comparing Probability of Target Attainment (PTA) of bolus, extended and continuous infusions of Ceftriaxone in simulated critically ill patients with varying degrees of renal function and serum albumin concentrations

Advisor(s)

Eyob Adane

Confirmation

1

Document Type

Poster

Location

ONU McIntosh Center; Activities Room

Start Date

11-4-2025 10:00 AM

End Date

11-4-2025 10:50 AM

Abstract

Background: Ceftriaxone (Rocephin®) is a third-generation cephalosporin with broad-spectrum activity against gram-positive and gram-negative organisms. Ceftriaxone is highly polar and extensively bound to serum albumin, thus pharmacokinetics may vary in critically ill patients due to impaired or augmented renal clearance, hypoalbuminemia, and abnormal protein binding. Our study evaluates the Probability of Target Attainment (PTA) across different renal functions and albumin levels using bolus, extended, and continuous infusions. Current guidelines recommend a 1–2 g dose over 30 minutes, but evidence for alternative infusion strategies remains insufficient.

Methods: Ceftriaxone pharmacokinetics were modeled using a two-compartment approach which incorporates saturable albumin binding and central compartment elimination. Population pharmacokinetics were derived from a multicenter study by Heffernan AJ et al. Monte Carlo simulations were conducted using Simulx2023R1 (Lixsoft SAS). Infusion methods included 30-minute, 2-hour, 3-hour, 4-hour, and continuous infusions (±500 mg loading dose). Both 1 g and 2 g doses were simulated at q24hr and q12hr intervals. Renal clearance (CrCl) values of 0, 45, 90, 130, 160, and 180 mL/min were assessed in patients with normal albumin (3.5 g/dL) and hypoalbuminemia (2.5 g/dL). Primary outcomes included %fCmin > MIC at 168 hours, %fT>MIC, and %fT>MBC. MIC and MBC were set at 0.5 mg/L and 2.0 mg/L, respectively.

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Apr 11th, 10:00 AM Apr 11th, 10:50 AM

Comparing Probability of Target Attainment (PTA) of bolus, extended and continuous infusions of Ceftriaxone in simulated critically ill patients with varying degrees of renal function and serum albumin concentrations

ONU McIntosh Center; Activities Room

Background: Ceftriaxone (Rocephin®) is a third-generation cephalosporin with broad-spectrum activity against gram-positive and gram-negative organisms. Ceftriaxone is highly polar and extensively bound to serum albumin, thus pharmacokinetics may vary in critically ill patients due to impaired or augmented renal clearance, hypoalbuminemia, and abnormal protein binding. Our study evaluates the Probability of Target Attainment (PTA) across different renal functions and albumin levels using bolus, extended, and continuous infusions. Current guidelines recommend a 1–2 g dose over 30 minutes, but evidence for alternative infusion strategies remains insufficient.

Methods: Ceftriaxone pharmacokinetics were modeled using a two-compartment approach which incorporates saturable albumin binding and central compartment elimination. Population pharmacokinetics were derived from a multicenter study by Heffernan AJ et al. Monte Carlo simulations were conducted using Simulx2023R1 (Lixsoft SAS). Infusion methods included 30-minute, 2-hour, 3-hour, 4-hour, and continuous infusions (±500 mg loading dose). Both 1 g and 2 g doses were simulated at q24hr and q12hr intervals. Renal clearance (CrCl) values of 0, 45, 90, 130, 160, and 180 mL/min were assessed in patients with normal albumin (3.5 g/dL) and hypoalbuminemia (2.5 g/dL). Primary outcomes included %fCmin > MIC at 168 hours, %fT>MIC, and %fT>MBC. MIC and MBC were set at 0.5 mg/L and 2.0 mg/L, respectively.