Ceftazidime/avibactam serum concentration in patients on ECMO

Area of Science:

• Pharmacology
• Critical Care Medicine
• Infectious Diseases

Background:

• Extracorporeal membrane oxygenation (ECMO) can alter drug pharmacokinetics, potentially leading to antibiotic underdosing and treatment failure.
• Limited data exist on the pharmacokinetics of newer antimicrobials like ceftazidime/avibactam in ECMO patients.

Purpose of the Study:

• To evaluate ceftazidime and avibactam blood levels in patients undergoing ECMO.
• To identify factors associated with potential underdosing of ceftazidime/avibactam during ECMO therapy.

Main Methods:

• A retrospective observational study was conducted on 14 ECMO patients who received ceftazidime/avibactam.
• Trough blood levels of ceftazidime and avibactam were measured and compared against European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints.
• Factors associated with underdosing were analyzed, with a focus on renal clearance.

Main Results:

• Twenty-three ceftazidime/avibactam trough levels were analyzed in patients receiving veno-venous ECMO for SARS-CoV-2 pneumonia.
• Ceftazidime levels were adequate in most patients (13/14), but 39% (9/23) of avibactam levels fell below the EUCAST breakpoint of 4 mg/L.
• Elevated renal clearance (creatinine clearance > 130 mL/min) was identified as a key factor associated with underdosing, observed in 70% of sub-therapeutic avibactam levels.

Conclusions:

• Ceftazidime/avibactam serum levels are generally above EUCAST breakpoints in ECMO patients, supporting standard dosing regimens.
• Increased renal clearance is a significant risk factor for ceftazidime/avibactam underdosing in ECMO patients.
• Close monitoring of antibiotic levels and renal function is crucial for optimizing ceftazidime/avibactam therapy in ECMO patients.