Drug Regimens of Novel Antibiotics in Critically Ill Patients with Varying Renal Functions: A Rapid Review.

Abstract

There is currently an increase in the emergence of multidrug-resistant bacteria (MDR) worldwide, requiring the development of novel antibiotics. However, it is not only the choice of antibiotic that is important in treating an infection; the drug regimen also deserves special attention to avoid underdosing and excessive concentrations. Critically ill patients often have marked variation in renal function, ranging from augmented renal clearance (ARC), defined as a measured creatinine clearance (CrCL) ≥ 130 mL/min*1.73 m2, to acute kidney injury (AKI), eventually requiring renal replacement therapy (RRT), which can affect antibiotic exposure. All novel beta-lactam (BLs) and/or beta-lactam/beta-lactamases inhibitors (BL/BLIs) antibiotics have specific pharmacokinetic properties, such as hydrophilicity, low plasma–protein binding, small volume of distribution, low molecular weight, and predominant renal clearance, which require adaptation of dosage regimens in the presence of abnormal renal function or RRT. However, there are limited data on the topic. The aim of this review was therefore to summarize available PK studies on these novel antibiotics performed in patients with ARC or AKI, or requiring RRT, in order to provide a practical approach to guide clinicians in the choice of the best dosage regimens in critically ill patients.