Pharmacokinetic/Pharmacodynamic Optimization and Therapeutic Drug Monitoring of Beta-Lactam Antibiotics in Abdominal Sepsis: Current Evidence, Challenges, and Clinical Perspectives—A Narrative Review
- 1Department of Woman, Child, General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
- 2Department of Critical Care, AORN Ospedali dei Colli, 80131 Naples, Italy
Abstract
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.
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BibTeX
@article{giurazza2026pharmacokineticpharmacodynamic,
title = {{Pharmacokinetic/Pharmacodynamic Optimization and Therapeutic Drug Monitoring of Beta-Lactam Antibiotics in Abdominal Sepsis: Current Evidence, Challenges, and Clinical Perspectives—A Narrative Review}},
author = {Roberto Giurazza and Gianluigi Cosenza and Marco Fiore and Salvatore Notaro and Pasquale Sansone and Vincenzo Pota and Francesco Coppolino and Francesca Piccialli and Maria Caterina Pace},
journal = {Journal of clinical medicine},
year = {2026},
month = oct,
doi = {10.3390/jcm15197697},
url = {https://europepmc.org/article/PMC/PMC13665887},
note = {CC BY},
}
RIS
TY - JOUR
TI - Pharmacokinetic/Pharmacodynamic Optimization and Therapeutic Drug Monitoring of Beta-Lactam Antibiotics in Abdominal Sepsis: Current Evidence, Challenges, and Clinical Perspectives—A Narrative Review
AU - Roberto Giurazza
AU - Gianluigi Cosenza
AU - Marco Fiore
AU - Salvatore Notaro
AU - Pasquale Sansone
AU - Vincenzo Pota
AU - Francesco Coppolino
AU - Francesca Piccialli
AU - Maria Caterina Pace
PY - 2026
DA - 2026/10/01
JO - Journal of clinical medicine
DO - 10.3390/jcm15197697
UR - https://europepmc.org/article/PMC/PMC13665887
AB - 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.
SN - 2077-0383
ER -