Evaluation of Standard Dosing for Selected Broad Spectrum Hydrophilic Antibiotics in Critically Ill Patients with Augmented Renal Clearance: An Observational Study

Background: Inappropriate antibiotics dosing in critically ill patients with augmented renal clearance (ARC) may be associated with pathogens resistance and worse outcomes. Unfortunately, studies regarding the relationship between ARC and clinical outcomes in patients treated with antibiotics medication are rare. The study aims to evaluate the efficacy and clinical outcomes of selected broad spectrum hydrophilic antibiotics (Meropenem, Imipinem, Piperacillin/Tazobactam) in augmented renal function critically ill patients with confirmed infections.Methods: A retrospective cohort study in critically ill patients who were admitted to intensive care units (ICUs) at King Abdulaziz Medical City (KAMC)-Riyadh and received broad-spectrum Hydrophilic antibiotics (Meropenem, Imipenem, or Piperacillin/Tazobactam) with confirmed infection. All the patients who met our inclusion criteria during the study period (01/01/2018 – 31/12/2019) were included. Eligible patients have been divided into two groups (augmented renal clearance (ARC) Vs. Non-ARC) according to the estimated creatinine clearance (CrCl) to assess pathogen eradication at 10-14 days. Results: A total of 2682 patients were screened; 133 patients were included in the study. The eradication of pathogen at 10-14 days in ARC group was non-inferior to non-ARC group (OR 1.08; 95% CI, 0.41–2.78 p = 0.88). The Resistance (OR 0.78; 95% CI, 0.25–2.40 p = 0.66), and Persistence after 3 days (OR 0.88; 95% CI, 0.35–2.18 p = 0.78) were not significantly different between the groups. In other words, patients with ARC have the same rate of resistance and persistence of pathogen after three days. There was no difference in the 30-day mortality between the two groups (OR 0.22; 95% CI, 0.04–1.40 p = 0.11). Also, there was no difference in the ICU length of stay (LOS) nor in hospital LOS between the two groups (22.0 days vs. 17.5 days, p = 0.37), and (51.0 days vs. 30.0 days, p = 0.07) respectively. Conclusion: Using standard dosing of hydrophilic broad-spectrum antibiotics in ARC patients was not inferior to non-ARC patients in terms of the pathogen eradication, resistance, and persistence. Further randomized clinical and interventional studies are required to confirm our findings.