PII-202 - HIGHER CLEARANCE WHILE ON HIGH-DOSE CONTINUOUS DIALYSIS IS ASSOCIATED WITH DECREASED TARGET ATTAINMENT OF PIPERACILLIN IN A PATIENT POST-KIDNEY TRANSPLANT FOR PRIMARY HYPEROXALURIA.

M. Hagenauer¹, H. Hambrick², K. Paice², K. Pavia², S. Tang Girdwood²; ¹Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA, ²Cincinnati Children's Hospital Medical Center.

Background: Continuous kidney replacement therapy (CKRT) is typically used to treat renal failure but may be used for toxin removal in patients with normal kidney function. CKRT can influence PK and target attainment (TA) of antibiotics, including piperacillin (PIP). Pediatric data suggest extracorporeal clearance (CLEC) from CKRT and kidney-provided CL both affect PIP CL (Thy, AAC, 2022). However, no analysis of free PIP PK in critically ill children with normal kidney function receiving CKRT has been published. We therefore evaluated free PIP CL and TA in a patient receiving high-dose CKRT for removal of oxalate.

Methods: Patient was an 8 yo 23.5 kg boy with chronic kidney disease stage IV due to primary hyperoxaluria receiving an en bloc liver/kidney transplant. Post-transplant, he was placed on continuous venovenous hemodialysis [CVVHD] with high total effluent flow rates, Qef, of ≈9000 mL/h/1.73 m2 (typical Qef = 2000 mL/h/1.73 m2) to treat systemic oxalosis. He was given piperacillin/tazobactam 100 mg/kg (88.9 mg/kg of PIP) q2h intra-op then q6h post-op as prophylaxis. Free concentrations were measured from residual plasma of clinical blood samples. Precision dosing software MwPharm++ and Bayesian estimation using a population PIP PK model in critically ill children (De Cock, JAC, 2017) adapted for free PIP (mean population CL: 19.11 L/h/70kg^0.75) were used to determine CL, volume of distribution (Vd), and percentage of time free concentrations were above 1-4 times minimum inhibitory concentration (% fT>1-4xMIC) using MIC of 8 mg/L (PIP breakpoint for Enterobacterales). Parameters in each period on and off CKRT were analyzed and compared.

Results: On average, PIP CL was 60% higher on versus off CKRT (5.53 vs 3.45 L/h, Table). fT>1xMIC was 100% and 98.4% for off and on CKRT, respectively. fT>4xMIC was 97.2% off CKRT, but only 61.4% fT>4xMIC on CKRT. CLEC was 38% of total patient CL while on CKRT and 46% of total CKRT dose (Qef).

Conclusion: PIP CL was higher on CKRT, and CKRT use was associated with markedly lower % fT>4xMIC. CLEC was less than half of total CL and of Qef, implying (1) the patient had substantial kidney elimination of PIP post-transplant and (2) increases in CVVHD CL beyond typical Qef may not result in parallel increases in PIP CL. Monitoring free PIP concentrations in children receiving CKRT may be warranted, especially for those with kidney function.