Pharmacokinetics, Pharmacodynamics, and Dosing Considerations of Novel β-Lactams and β-Lactam/β-Lactamase Inhibitors in Critically Ill Adult Patients: Focus on Obesity, Augmented Renal Clearance, Renal Replacement Therapies, and Extracorporeal Membrane Oxygenation

Dana Bakdach; Reem Elajez; Abdul Rahman Bakdach; Ahmed Awaisu; Gennaro De Pascale; Ali Ait Hssain

doi:10.3390/jcm11236898

Pharmacokinetics, Pharmacodynamics, and Dosing Considerations of Novel β-Lactams and β-Lactam/β-Lactamase Inhibitors in Critically Ill Adult Patients: Focus on Obesity, Augmented Renal Clearance, Renal Replacement Therapies, and Extracorporeal Membrane Oxygenation

J Clin Med. 2022 Nov 22;11(23):6898. doi: 10.3390/jcm11236898.

Authors

Dana Bakdach¹, Reem Elajez², Abdul Rahman Bakdach³, Ahmed Awaisu⁴, Gennaro De Pascale^{5

6}, Ali Ait Hssain⁷

Affiliations

¹ Department of Clinical Pharmacy, Critical Care, Hamad Medical Corporation, Doha 3050, Qatar.
² Department of Pharmacy, Infectious Diseases, Hamad Medical Corporation, Doha 3050, Qatar.
³ School of Medicine, Jordan University of Science and Technology, Irbid 3030, Jordan.
⁴ Clinical Pharmacy and Practice, College of Pharmacy, QU Health, Qatar University, Doha 2713, Qatar.
⁵ Department of Anesthesiology, Intensive Care and Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
⁶ Dipartimento di Scienze Biotecnologiche di Base Cliniche Intensivologiche e Perioperatorie, Universita' Cattolica del Sacro Cuore, 00168 Rome, Italy.
⁷ Department of Medicine, Critical Care Services, Hamad Medical Corporation, P.O. Box 305, Doha 3050, Qatar.

Abstract

Objective: Dose optimization of novel β-lactam antibiotics (NBLA) has become necessary given the increased prevalence of multidrug-resistant infections in intensive care units coupled with the limited number of available treatment options. Unfortunately, recommended dose regimens of NBLA based on PK/PD indices are not well-defined for critically ill patients presenting with special situations (i.e., obesity, extracorporeal membrane oxygenation (ECMO), augmented renal clearance (ARC), and renal replacement therapies (RRT)). This review aimed to discuss and summarize the available literature on the PK/PD attained indices of NBLA among critically ill patients with special circumstances.

Data sources: PubMed, MEDLINE, Scopus, Google Scholar, and Embase databases were searched for studies published between January 2011 and May 2022.

Study selection and data extraction: Articles relevant to NBLA (i.e., ceftolozane/tazobactam, ceftazidime/avibactam, cefiderocol, ceftobiprole, imipenem/relebactam, and meropenem/vaborbactam) were selected. The MeSH terms of "obesity", "augmented renal clearance", "renal replacement therapy", "extracorporeal membrane oxygenation", "pharmacokinetic", "pharmacodynamic" "critically ill", and "intensive care" were used for identification of articles. The search was limited to adult humans' studies that were published in English. A narrative synthesis of included studies was then conducted accordingly.

Data synthesis: Available evidence surrounding the use of NBLA among critically ill patients presenting with special situations was limited by the small sample size of the included studies coupled with high heterogeneity. The PK/PD target attainments of NBLA were reported to be minimally affected by obesity and/or ECMO, whereas the effect of renal functionality (in the form of either ARC or RRT) was more substantial.

Conclusion: Critically ill patients presenting with special circumstances might be at risk of altered NBLA pharmacokinetics, particularly in the settings of ARC and RRT. More robust, well-designed trials are still required to define effective dose regimens able to attain therapeutic PK/PD indices of NBLA when utilized in those special scenarios, and thus aid in improving the patients' outcomes.

Keywords: augmented renal clearance; critical care; extracorporeal membrane oxygenation; novel beta-lactam antibiotics; obesity; pharmacodynamics; pharmacokinetics; renal replacement.

Publication types

Review

Grants and funding

This research received no external funding.