# Antimicrobial Dosing During Continuous Venovenous Hemodiafiltration in Septic Shock Patients: A Prospective, Multicenter Study Protocol

## TL;DR

This study aims to improve antibiotic dosing for septic shock patients on kidney support to enhance treatment outcomes.

## Contribution

It introduces a protocol for developing pharmacokinetic models for beta-lactam antibiotics in septic shock patients undergoing CVVHDF.

## Key findings

- Pharmacokinetic models will optimize beta-lactam dosing in septic shock patients on CRRT.
- LC-MS/MS and Monte Carlo simulations will determine accurate drug concentrations and PK/PD breakpoints.
- Improved dosing strategies may reduce antibiotic resistance and enhance treatment outcomes.

## Abstract

Background: Sepsis is a major global health issue and the leading cause of death in critically ill patients, with rising incidence and associated healthcare costs. Early administration of antibiotic therapy is crucial, but increasing antibiotic resistance poses a threat. Beta-lactam antibiotics, commonly used as a first-line therapy option against sepsis, often demonstrate unpredictable concentrations due to pharmacokinetic and pharmacodynamic changes in critically ill patients. Acute kidney injury (AKI) affects a significant portion of septic patients, and continuous renal replacement therapy can further complicate treatment by reducing antibiotic levels and, consequently, increasing antibiotic resistance risk. Objectives: To develop pharmacokinetic/pharmacodynamic models for beta-lactam antibiotics in septic shock patients undergoing continuous renal replacement therapy (CRRT), with the goal of optimizing antibiotic dosing and then improving treatment outcomes. Methods: Septic shock Caucasian adult patients treated with beta-lactams and who have undergone major surgery in AKI failure that requires CRRT will be eligible with previous informed written consent. CRRT will be performed exclusively using Continuous Venovenous Hemodiafiltration (CVVHDF) modality. Antimicrobial determination analyses will be carried out with LC-MS/MS. Further calculation of pharmacokinetic parameters and determination of PK/PD breakpoints will be made using Monte Carlo simulation. Conclusions: The expected results from this study will lead to a better understanding of the pharmacokinetics of beta-lactam antibiotics in critically ill patients with AKI and septic shock undergoing CVVHDF, allowing for improved therapeutic strategies.