Renal Impact of a High-Loading Dose of Amikacin in Critically Ill Patients Publisher



L Mahmoudi LALEH ; A Ahmadi AREZOO ; M Mahibirjand MOTAHARE ; E Alemzadeh EFFAT ; P Askari PARVIN ; R Niknam RAMIN ; M Mojtahedzadeh MOJTABA
Source: Pharmaceutical Sciences Published:2025

Abstract

Background: Aminoglycosides are potent bactericidal antibiotics primarily employed for gram-negative infections. However, they face limitations due to potential renal toxicity when administered at high doses. This study aimed to assess the nephrotoxicity of amikacin (AMK) at two distinct dosage levels over seven days in critically ill patients, utilizing renal-specific biomarkers. Methods: Critically ill patients with sepsis, severe sepsis, or septic shock were randomly assigned to two treatment groups receiving AMK in combination with a broad-spectrum β-lactam antibiotic according to antibiogram results. Disease severity was assessed using the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores. Renal function was monitored through serum creatinine (SCr) and kidney injury biomarkers (NGAL and IL-18) measurements. Results: Among the 40 patients completing the study, the two groups had no significant differences in APACHE II (P=0.39) and SOFA scores (P=0.30). Baseline plasma creatinine levels exhibited no significant within-group differences. While NGAL levels in group 1(high dose AMK) significantly increased on day 3, no significant differences were observed between the groups in all four measurements (P=0.03). Urinary IL-18 levels within groups demonstrated a significant increase peaking on day 3, with no significant within-group differences over the 7-day follow-up. Conclusion: The findings suggest that higher doses of AMK may be administered with a similar effect of low-dose AMK on renal function, as assessed by the RIFLE criteria (Risk, Injury, Failure, Loss, and End-stage kidney disease), a classification system used to evaluate acute kidney injury (AKI) severity in critically ill patients with sepsis. © 2025 Elsevier B.V., All rights reserved.