Software- and TDM-Guided Dosing of Meropenem Promises High Rates of Target Attainment in Critically Ill Patients

Area of Science:

• Pharmacology
• Critical Care Medicine
• Infectious Diseases

Background:

• Beta-lactam antibiotic underdosing is common in critically ill patients, especially those with sepsis.
• Optimal meropenem dosing strategies remain a challenge, impacting treatment efficacy.
• This study addresses the need for improved meropenem dosing in intensive care settings.

Purpose of the Study:

• To evaluate the effectiveness of software-guided empiric meropenem dosing (CADDy) combined with therapeutic drug monitoring (TDM).
• To assess the achievement of target meropenem concentrations (8-16 mg/L) in critically ill patients.
• To determine if TDM-guided adjustments can optimize meropenem exposure and minimize toxicity.

Main Methods:

• Retrospective analysis of 91 critically ill patients receiving continuous infusion meropenem.
• Utilized the CADDy software for initial empiric dosing.
• Performed routine meropenem serum concentration measurements and expert clinical pharmacological interpretations for TDM-guided adjustments.

Main Results:

• Initially, 60% of patients achieved target meropenem concentrations (8-16 mg/L) using the CADDy software.
• 23% had moderately high (16-24 mg/L) and 10% had potentially harmful (>24 mg/L) concentrations within 48 hours.
• No patient had sub-therapeutic concentrations (<2 mg/L) with software-guided dosing.
• TDM-guided dose adjustments significantly increased therapeutic drug exposure to 70%, with no concentrations >24 mg/L.

Conclusions:

• Software-guided empiric dosing of meropenem shows promise in achieving therapeutic concentrations.
• The combination of dosing software and TDM significantly enhances meropenem exposure in septic patients.
• This integrated approach improves the safety and efficacy of meropenem therapy in critically ill patients with sepsis and septic shock.