ARC in Critical Ill OLT Recipients: True Prevalence, Risk Factors, and Impact on Early Aggressive PK/PD Target Non‐Attainment of CI Beta‐Lactam Therapy for Posttransplant Gram‐Negative Infections

Background: To assess the true prevalence and the risk factors of augmented renal clearance (ARC) in critical orthotopic liver transplant (OLT) recipients and its impact on early aggressive pharmacokinetic/pharmacodynamic (PK/PD) target non-attainment of continuous infusion (CI) beta-lactams. Methods: OLT recipients without renal dysfunction and undergoing one or more measured creatinine clearance (mCLCr) assessments in the first 30 days posttransplant were retrospectively included. Reliability of three different eGFR formulas (Cockcroft-Gault, 2021, CKD-EPI, and MDRD) in estimating mCLCr was tested. Univariate analyses compared the clinical features of ARC versus non-ARC patients and the severity of the clinical conditions during ARC versus non-ARC episodes in the whole cohort. In patients receiving CI beta-lactam therapy, risk factors for early aggressive PK/PD target non-attainment were investigated. Results: Among 450 critical OLT recipients, 112 were included. The true prevalence of ARC was 23.2%. ARC versus non-ARC patients were younger (p = 0.003), had lower MELD score (p = 0.001), received lower number of intraoperative blood transfusions (p = 0.007), and had a lower need for venovenous bypass technique (p = 0.024). ARC episodes occurred more frequently in patients having lower SOFA score (p = 0.005) and lower median serum creatinine levels (p < 0.001). None of the eGFR formulas properly estimated mCLCr. In the subset of 50 OLT recipients receiving 60 CI beta-lactam treatment courses, ARC was the only factor associated with early aggressive PK/PD target non-attainment (p = 0.018). Conclusions: ARC is a quite prevalent condition among critical OLT recipients, which may hinder early aggressive PK/PD target attainment when using standard beta-lactams dosing regimens, regardless of delivery by CI.