J Extra Corpor Technol 2023 , 55 , 159 – 166 Ó The Author ( s ), published by EDP Sciences , 2023 https :// doi . org / 10.1051 / ject / 2023035
Available online at : ject . edpsciences . org
ORIGINAL ARTICLE
Meropenem extraction by ex vivo extracorporeal life support circuits
Christopher Cole Honeycutt ( BS ) 1 , Charles Griffin McDaniel ( BS ) 1 , Autumn McKnite ( BS ) 2 , 3 , J . Porter Hunt ( PhD ) 3 , Aviva Whelan ( MD ) 3 , 4 , Danielle J . Green ( MD ) 3 , 4 , and Kevin M . Watt ( MD , PhD ) 3 , 4 ,*
1 Duke University , Durham , North Carolina , USA 2 Department of Pharmacology and Toxicology , University of Utah College of Pharmacy , Salt Lake City , Utah , USA 3 Division of Clinical Pharmacology , Department of Pediatrics , University of Utah Medical Center , Salt Lake City , Utah , USA 4 Division of Critical Care , Department of Pediatrics , University of Utah Medical Center , Salt Lake City , Utah , USA
Received 29 March 2023 , Accepted 28 July 2023
Abstract – Background : Meropenem is a broad-spectrum carbapenem-type antibiotic commonly used to treat critically ill patients infected with extended-spectrum b-lactamase ( ESBL ) -producing Enterobacteriaceae . As many of these patients require extracorporeal membrane oxygenation ( ECMO ) and / or continuous renal replacement therapy ( CRRT ), it is important to understand how these extracorporeal life support circuits impact meropenem pharmacokinetics . Based on the physicochemical properties of meropenem , it is expected that ECMO circuits will minimally extract meropenem , while CRRT circuits will rapidly clear meropenem . The present study seeks to determine the extraction of meropenem from ex vivo ECMO and CRRT circuits and elucidate the contribution of different ECMO circuit components to extraction . Methods : Standard doses of meropenem were administered to three different configurations ( n = 3 per configuration ) of blood-primed ex vivo ECMO circuits and serial sampling was conducted over 24 h . Similarly , standard doses of meropenem were administered to CRRT circuits ( n = 4 ) and serial sampling was conducted over 4 h . Meropenem was administered to separate tubes primed with circuit blood to serve as controls to account for drug degradation . Meropenem concentrations were quantified , and percent recovery was calculated for each sample . Results : Meropenem was cleared at a similar rate in ECMO circuits of different configurations ( n = 3 ) and controls ( n = 6 ), with mean ( standard deviation ) recovery at 24 h of 15.6 % ( 12.9 ) in Complete circuits , 37.9 % ( 8.3 ) in Oxygenator circuits , 47.1 % ( 8.2 ) in Pump circuits , and 20.6 % ( 20.6 ) in controls . In CRRT circuits ( n = 4 ) meropenem was cleared rapidly compared with controls ( n = 6 ) with a mean recovery at 2 h of 2.36 % ( 1.44 ) in circuits and 93.0 % ( 7.1 ) in controls . Conclusion : Meropenem is rapidly cleared by hemodiafiltration during CRRT . There is minimal adsorption of meropenem to ECMO circuit components ; however , meropenem undergoes significant degradation and / or plasma metabolism at physiological conditions . These ex vivo findings will advise pharmacists and physicians on the appropriate dosing of meropenem .
Key words : Extracorporeal membrane oxygenation , Continuous renal replacement therapy , Drug extraction , Meropenem , Pharmacokinetics .
Introduction
Meropenem is a broad-spectrum carbapenem-type antibiotic that is routinely used as an empiric treatment of lifethreatening infections in hospitalized adult and pediatric patients [ 1 ]. It is FDA-approved for the treatment of complicated skin , skin structure , and intra-abdominal infections [ 1 ]. It is also approved for the treatment of bacterial meningitis in pediatric patients 3 months of age and older [ 1 ]. Because of
* Corresponding author : kevin . watt @ hsc . utah . edu these indications , meropenem is often used in critically ill patients on extracorporeal life support ( ECLS ) such as extracorporeal membrane oxygenation ( ECMO ) or continuous renal replacement therapy ( CRRT ).
While ECLS can be lifesaving , mortality often exceeds 40 % [ 2 – 6 ]. This high level of mortality is multifactorial and includes complications from the underlying critical illness ( e . g ., multiorgan failure ) and direct complications from ECLS support ( e . g ., anticoagulation-related bleeding ). In addition , some of this mortality may be attributed to suboptimal drug dosing , resulting from ECLS-induced changes in pharmacokinetics [ 7 – 10 ].
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