Antimicrobial Disposition During Pediatric Continuous Renal Replacement Therapy Using an Ex Vivo Model

Area of Science:

• Pharmacokinetics and Pharmacology
• Pediatric Critical Care
• Renal Replacement Therapy

Background:

• Limited data exists on how continuous renal replacement therapy (CRRT) affects antimicrobial dosing requirements in pediatric patients.
• Understanding drug-circuit interactions is crucial for optimizing antimicrobial therapy in critically ill children undergoing CRRT.

Purpose of the Study:

• To evaluate the pharmacokinetics of commonly used antimicrobials in an ex vivo pediatric CRRT model.
• To determine the disposition and clearance of specific antimicrobials during CRRT at varying clearance rates.

Main Methods:

• An ex vivo pediatric CRRT circuit was utilized, simulating hemodiafiltration mode for a 10 kg child.
• Five antimicrobials (meropenem, piperacillin, liposomal amphotericin B, caspofungin, voriconazole) were tested at three CRRT clearance rates (0, 20, 40 mL/kg/hr).
• Antimicrobial concentrations were measured using liquid chromatography-mass spectrometry, and pharmacokinetic modeling was applied.

Main Results:

• Antimicrobial adsorption to the CRRT circuit ranged from 13% to 27%.
• Meropenem, piperacillin, and voriconazole showed significant CRRT clearance, increasing with higher CRRT clearance rates.
• Liposomal amphotericin B and caspofungin exhibited minimal circuit clearance, unaffected by CRRT clearance rates.

Conclusions:

• Drug-circuit interactions during CRRT significantly influence antimicrobial pharmacokinetics in children.
• Meropenem, piperacillin, and voriconazole are cleared by CRRT, requiring dose adjustments.
• Amphotericin B and caspofungin show minimal CRRT clearance, suggesting different dosing considerations.