Augmented Renal Clearance (ARC), defined as a supraphysiological increase in renal function, is frequently observed in critically ill patients, particularly those with acute brain injury. ARC complicates the management of renally eliminated drugs, specifically beta-lactam antibiotics, by enhancing drug clearance and thereby increasing the risk of underdosing and therapeutic failure. Although pharmacological therapeutic drug monitoring (TDM) is recommended to optimize dosing, it remains limited by issues of accessibility, highlighting the need for alternative approaches to identify at-risk patients and adjust dosing based on renal function.
Early identification of patients at risk for subtherapeutic beta-lactam plasma concentrations could enable timely dose adjustments. A combined assessment of renal function and beta-lactam TDM could enhance our understanding of the kinetics of both parameters. These data may support the development of predictive models capable of proposing individualized dosing regimens based on renal function.
Optimizing beta-lactam plasma concentrations in this patient population could improve infection management and potentially enhance clinical outcomes.
Adult patients (≥18 years old)
Admitted to the intensive care unit for acute brain injury
Exhibiting Augmented Renal Clearance (ARC), defined by a urinary creatinine clearance (ClCrU) greater than 130 mL/min/1.73 m² on at least one measurement
Receiving Therapeutic Drug Monitoring (TDM)-guided treatment with one of the following beta-lactam antibiotics: amoxicillin/clavulanic acid, cefotaxime, piperacillin/tazobactam, cefepime, or meropenem
Estimated life expectancy <24 hours
Patients who have expressed opposition to study participation
Patients under legal protection (guardianship, curatorship, or court protection)
Patients currently in an exclusion period determined by participation in another study
The population studied included patients admitted to the intensive care unit with acute brain injury (of traumatic, vascular, infectious or immunological origin), presenting a profile of HCR and receiving antibiotic treatment with betalactam
Cohort
Prospective
Not listed
Plasma betalactam underdosing
Development of a predictive model for plasma beta-lactam underdosing in critically ill patients with acute brain injury and renal hyperclearance, receiving beta-lactam therapy for an ongoing infectious episode. Plasma beta-lactam concentrations will be measured 24 hours after initiation of antibiotic therapy, and subsequently every 48 hours, or in cases of underdosing, overdosing, antibiotic switch, or significant changes in renal function.
Evolution of Augmented Renal Clearance
Assessment of urinary creatinine clearance based on urine collection (8, 12, or 24-hour collection depending on center practices).
Evolution of plasma Beta-lactam Concentration
Monitoring of total plasma beta-lactam concentrations obtained through Therapeutic Drug Monitoring during the intensive care stay
Relationship Between Plasma Underdosing Intensity and Level of Augmented Renal Clearance (ARC)
Characterization of the intensity of plasma beta-lactam underdosing for each antibiotic molecule relative to the degree of ARC.
Beta-lactam Dosing According to Augmented Renal Clearance Level.
Development of a dosing nomogram for beta-lactam antibiotics tailored to the degree of ARC.
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