Pharmacokinetic Changes of Ceftazidime–Avibactam with Veno-Arterial Extracorporeal Membrane Oxygenation in a Critically Ill Patient with Severe Renal Impairment: A Case Report

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an advanced life support therapy, but evidence regarding its impact on the pharmacokinetic (PK) characteristics of ceftazidime-avibactam (CAZ-AVI) is still limited. This study reports a 47-year-old man who developed severe renal impairment during VA-ECMO support following cardiac arrest and was treated with CAZ-AVI for pneumonia caused by carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP). Therapeutic drug monitoring (TDM) was performed before and after VA-ECMO weaning. PK analysis showed that, compared to the period with VA-ECMO support, the clearances (CLs) of CAZ and AVI increased after VA-ECMO weaning, resulting in 31.1% and 34.5% decreases in systemic exposure to CAZ and AVI, respectively. Despite these reductions, trough concentrations remained above the PK/PD targets of 100% fT > 20.0 mg/L for CAZ and 100% fT > 4.0 mg/L for AVI, respectively. Unfortunately, the patient's renal function progressively worsened, complicated by hyperkalemia, and he experienced a second cardiac arrest on day 5 after ECMO weaning, resulting in death. These findings suggest that in patients undergoing prolonged VA-ECMO support, the exposure of CAZ-AVI may decline after ECMO weaning, underscoring the need for reassessment of dosing strategies.