Piperacillin Pharmacokinetics in a Pediatric Patient With Primary Hyperoxaluria Receiving High-Dose Continuous Dialysis Post Liver-Kidney Transplant

Continuous kidney replacement therapy (CKRT) can influence pharmacokinetics (PK), including clearance (CL) of antibiotics like piperacillin (PIP). Both CKRT intensity, or “dialysis dose,” and residual kidney function can alter PIP PK and pharmacodynamic (PD) target attainment (TA), defined by the percentage of time free PIP concentrations exceed the minimum inhibitory concentration (% fT > MIC). In existing reports, children receiving PIP and CKRT are usually oligoanuric, so PIP PK/PD in non-oligoanuric patients receiving high-intensity CKRT is unknown. This report analyzes free PIP PK/PD in a child with robust kidney function who received 30-minute infusions of 100 mg/kg PIP-tazobactam every 6 hours while on high-intensity CKRT after liver-kidney transplant for primary hyperoxaluria. Model-informed PK software was used to estimate PK/PD parameters for periods on and off CKRT. PIP CL on CKRT was 66% higher than off CKRT (5.59 L/hr vs 3.36 L/hr). Nearly 100% fT > 1xMIC (using 8 mg/L for Enterobacterales) was achieved whether on or off CKRT, but only 60% fT > 4xMIC was achieved on CKRT. CKRT CL was 40% of total CL on CKRT and 51% of the CKRT dialysis dose, suggesting PIP elimination was mostly renal despite high-intensity dialysis. Monitoring of free PIP concentrations may help ensure proper TA in non-oligoanuric patients receiving high-dose CKRT.