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

Zhuowei Shen,1 Hui Qin,1 Qian Li,2 Xiaohong Mao1 1Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 2Emergency and Critical Care Center, Department of Emergency Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Xiaohong Mao, Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China, Email [email protected] Qian Li, Emergency and Critical Care Center, Department of Emergency Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China, Email [email protected]: 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 Klebsiella pneumoniae (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.Keywords: Ceftazidime, Avibactam, Pharmacokinetics, VA-ECMO