Practical considerations for individualizing drug dosing in critically ill adults receiving renal replacement therapy

Abstract

Critically ill patients with sepsis admitted to the intensive care unit (ICU) often present with or develop renal dysfunction requiring renal replacement therapy (RRT) in addition to antimicrobial therapy. While early and appropriate antimicrobials for sepsis have been associated with an increased probability of survival, adequate dosing is also required in these patients. Adequate dosing of antimicrobials refers to dosing strategies that achieve serum drug levels at the site of infection that are able to provide a microbiological and/or clinical response while avoiding toxicity from excessive antibiotic exposure. Therapeutic drug monitoring (TDM) is the recommended strategy to achieve this goal, however, TDM is not routinely available in all ICUs and for all antimicrobials. In the absence of TDM, clinicians are therefore required to make dosing decisions based on the clinical condition of the patient, the causative organism, the characteristics of RRT, and an understanding of the physicochemical properties of the antimicrobial. Pharmacokinetics (PK) of antimicrobials can be highly variable between critically ill patients and also within the same patient over the course of their ICU stay. The initiation of RRT, which can be in the form of intermittent hemodialysis, continuous, or prolonged intermittent therapy, further complicates the predictability of drug disposition. This variability highlights the need for individualized dosing. This review highlights the practical considerations for the clinician for antimicrobial dosing in critically ill patients receiving RRT.

Precision medicine in the ICU: One size fits one patient

“…Contributions from an international team of thought leaders and experts provide a detailed overview of ICU topics in a systems-based approach. [1][2][3][4][5][6][7][8] Additionally, original research manuscripts aimed toward optimizing dosing strategies provide valuable insight for bedside clinicians when crafting drug regimens. [9][10][11][12] The vast heterogeneity encountered with ICU patients provides the optimal setting to showcase thevalueofprecisionmedicine.Asclinicians,wemustembracethis step forward to better identify the right therapy for the right patient at the right time.…”