"The Impact of Meropenem Strategy on Treatment Efficacy in Sepsis and Septic Shock : Extended vs. Intermittent Dosing in the ICU"

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock should be considered a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities significantly increase mortality risk compared to sepsis alone.

Beta-lactam antibiotics exhibit broad-spectrum activity against most Gram-positive and Gram-negative bacteria, making them a key component of sepsis treatment. Their bactericidal effects are time-dependent, meaning efficacy depends on maintaining free drug concentrations above the minimum inhibitory concentration of the target pathogen for an optimal duration.

In clinical practice, beta-lactams are typically administered via intermittent infusion. However, critically ill patients often experience altered pharmacokinetics due to changes in renal clearance, protein binding, fluid balance, and volume distribution. This variability can lead to unpredictable drug concentrations, increasing the risk of subtherapeutic antibiotic exposure.

Existing studies suggest that continuous infusion may enhance beta-lactam efficacy by maintaining drug concentrations above the minimum inhibitory concentration for longer periods, optimizing pharmacokinetic and pharmacodynamic targets. Some meta-analyses and small randomized controlled trials report reduced mortality and improved clinical cure rates with continuous infusion, while others show no significant difference. However, differences in dosing regimens, patient populations, and pharmacokinetic variability in critically ill patients make it difficult to draw firm conclusions.