Pharmacokinetic/Pharmacodynamic Optimization and Therapeutic Drug Monitoring of Beta-Lactam Antibiotics in Abdominal Sepsis: Current Evidence, Challenges, and Clinical Perspectives-A Narrative Review.

Background

Abdominal sepsis is associated with profound pharmacokinetic (PK) alterations that make standard beta-lactam dosing regimens potentially inadequate in critically ill patients. Increased volume of distribution, hypoalbuminemia, augmented renal clearance (ARC), acute kidney injury (AKI) and the PK complexity of the peritoneal compartment collectively impair the ability of conventional dosing to achieve pharmacodynamic (PD) targets. These PK derangements are clinically relevant but incompletely characterized in intra-abdominal infections (IAI)- specific cohorts, as most available data derive from broader critically ill populations. Beta-lactam antibiotics, the cornerstone therapy in IAIs, are particularly susceptible to these alterations, especially in the context of multidrug-resistant (MDR) pathogens.

Methods

We conducted a structured narrative review of the literature published between 2010 and 2026, searching PubMed and Embase using terms related to pharmacokinetics, pharmacodynamics, therapeutic drug monitoring, beta-lactam antibiotics, abdominal sepsis, and intra-abdominal infection in critically ill patients. Additional references were identified through manual bibliography screening, including seminal studies predating the search window. No formal systematic review methodology was applied.

Results

PK/PD optimization in abdominal sepsis can be organized around four proposed domains: extended or continuous infusion of beta-lactams to maximize the time above the minimum inhibitory concentration; therapeutic drug monitoring (TDM) to guide individualized dose adjustment in the presence of ARC, AKI, or continuous renal replacement therapy (CRRT); tailored dose optimization during CRRT; and target attainment analysis against MDR organisms. Extended and continuous infusions improve PD target attainment and are associated with improved outcomes in some observational studies, although prospective IAI-specific evidence is lacking and the evidence supporting these strategies derives largely from broader intensive care unit populations.

Conclusions

In abdominal sepsis, integrating PK/PD principles and TDM-guided dosing represents a pharmacologically rational strategy to optimize beta-lactam exposure and improve target attainment against MDR pathogens. Rigorous IAI-specific prospective studies are needed to establish definitive TDM-guided dosing protocols and translate these pharmacological strategies in this high-acuity setting.