Antimicrobial Exposures in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation.

Shekar, Kiran; Abdul-Aziz, Mohd H; Cheng, Vesa; Burrows, Fay; Buscher, Hergen; Cho, Young-Jae; Corley, Amanda; Diehl, Arne; Gilder, Eileen; Jakob, Stephan M; Kim, Hyung-Sook; Levkovich, Bianca J; Lim, Sung Yoon; McGuinness, Shay; Parke, Rachael; Pellegrino, Vincent; Que, Yok-Ai; Reynolds, Claire; Rudham, Sam; Wallis, Steven C; ... (2023). Antimicrobial Exposures in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation. American journal of respiratory and critical care medicine, 207(6), pp. 704-720. American Thoracic Society 10.1164/rccm.202207-1393OC

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RATIONALE

Data are suggesting that altered antimicrobial concentrations are likely during extracorporeal membrane oxygenation (ECMO).

OBJECTIVES

The primary aim of this analysis was to describe the pharmacokinetics of antimicrobials in critically ill adult patients receiving ECMO. Our secondary aim was to determine whether current antimicrobial dosing regimens achieve both effective and safe exposure.

METHODS

This study was a prospective, open-labelled, pharmacokinetic study in six intensive care units from Australia, New Zealand, South Korea and Switzerland. Serial blood samples were collected over a single dosing interval during ECMO for eleven antimicrobials. Pharmacokinetic parameters were estimated using non-compartmental methods. Adequacy of antimicrobial dosing regimens were evaluated using pre-defined concentration exposures associated with maximal clinical outcomes and minimal toxicity risks.

MEASUREMENTS AND MAIN RESULTS

We included 993 blood samples from 85 patients. The mean age was 44.7 ± 14.4 years and 61.2% were males. Thirty-eight patients (44.7%) were receiving renal replacement therapy (RRT) during first pharmacokinetic sampling. Large variations (coefficient of variation of ≥30%) in antimicrobial concentrations were seen leading to more than five-fold variations in all PK parameters across all study antimicrobials. Overall, 70 (56.5%) concentration profiles achieved the pre-defined target concentration and exposure range. Target attainment rates were not significantly different between modes of ECMO and RRT. Poor target attainment was observed across the most frequently used antimicrobials for ECMO patients, including for oseltamivir (33.3%), piperacillin (44.4%), and vancomycin (27.3%).

CONCLUSION

Antimicrobial pharmacokinetics were highly-variable in critically ill patients receiving ECMO leading to poor target attainment rates.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic of Intensive Care
UniBE Contributor:	Jakob, Stephan, Que, Yok-Ai, Zacharias, David
Subjects:	600 Technology > 610 Medicine & health
ISSN:	1535-4970
Publisher:	American Thoracic Society
Language:	English
Submitter:	Pubmed Import
Date Deposited:	11 Oct 2022 13:07
Last Modified:	16 Mar 2023 00:12
Publisher DOI:	10.1164/rccm.202207-1393OC
PubMed ID:	36215036
Uncontrolled Keywords:	antifungals antiviral critical illness pharmacokinetics renal replacement therapy
URI:	https://boris.unibe.ch/id/eprint/173643