Evaluation of Meropenem Extended Versus Intermittent Infusion Dosing Protocol in Critically Ill Patients

Area of Science:

• Pharmacology and Critical Care Medicine
• Antimicrobial Stewardship
• Infectious Diseases

Background:

• Altered pharmacokinetics/pharmacodynamics in critically ill patients necessitate optimized antibiotic dosing.
• Extended infusion (EI) of β-lactams can enhance drug exposure and clinical outcomes.
• Meropenem is a critical antibiotic for severe sepsis and septic shock.

Purpose of the Study:

• To evaluate the impact of an extended infusion meropenem (EIM) protocol versus an intermittent infusion meropenem (IIM) protocol on ICU mortality and clinical response.
• To optimize meropenem dosing in critically ill patients with severe sepsis/septic shock.

Main Methods:

• Retrospective study comparing EIM (1 g over 3 hours every 8 hours) with IIM (500 mg over 30 minutes every 6 hours) in a Medical Intensive Care Unit.
• Patient cohorts were analyzed for ICU mortality, clinical response, vasopressor use, and laboratory parameters.
• Statistical analysis included hazard ratios adjusted for Sequential Organ Failure Assessment (SOFA) score.

Main Results:

• The EIM group showed significantly lower ICU mortality (19% vs. 37%, P = .032) and higher clinical response rates (83% vs. 46%, P < .01).
• Patients on EIM had shorter vasopressor durations (2 vs. 3 days, P = .038) and higher white blood cell normalization rates (87% vs. 51%, P < .01).
• Intermittent meropenem infusion (IIM) was an independent risk factor for ICU mortality (HR: 3.653, P = .001).

Conclusions:

• Extended infusion meropenem (EIM) significantly improved mortality and clinical outcomes in patients with severe sepsis/septic shock and susceptible gram-negative pathogens.
• The EIM protocol represents a more effective meropenem dosing strategy in critically ill populations compared to IIM.
• Antimicrobial Stewardship Programs can effectively implement EI protocols to optimize antibiotic therapy.