Comparison of Pharmacokinetic/Pharmacodynamic Parameters and Clinical Outcomes of Vancomycin Administered in Two Different Dosage Regimens in Patients with Acute Kidney Injury.

Abstract

Background: Vancomycin is commonly used in intensive care units (ICUs), but its optimal dosage in patients with acute kidney injury (AKI) remains uncertain. This study aimed to evaluate vancomycin's pharmacokinetic and pharmacodynamic (PK/PD) properties, therapeutic target attainment area under the curve/minimum inhibitory concentration (AUC/MIC ≥ 400) under two dosage regimens, and the need for dosage adjustments in AKI.

Objectives: The primary objective was to assess the proportion of patients achieving a therapeutic AUC/MIC ratio of 400 - 600 mg.h/L and to analyze PK/PD parameters, including volume of distribution (Vd), half-life (T½), and elimination constant (K). The secondary objective was to evaluate kidney function decline, the requirement for renal replacement therapy (RRT), and mortality rates.

Methods: A single-blind randomized clinical trial (IRCT20130917014693N16) was conducted at Loghman Hakim Hospital, Tehran, Iran. Patients over 18 years of age who received at least four doses of vancomycin and developed AKI were included in the study. Eligible patients were randomly allocated into either the intervention or control groups. The intervention group received vancomycin without any dose adjustment, while the control group's vancomycin dose was adjusted based on daily vancomycin clearance, following the standard protocol in our ICU. Daily serum creatinine, vancomycin peak and trough levels, and clinical outcomes were monitored.

Results: Twenty patients were included in the study. There were no significant differences in baseline data between the two groups. Among the 20 patients, the mean AUC/MIC was higher in the intervention group (345.80 ± 31.95) compared to the control group (251.43 ± 83.10, P = 0.005), although the therapeutic target was not achieved in either group. Despite the lower AUC in the control group, mortality rates, AKI progression, and the need for hemodialysis were comparable between groups (P = 0.29).

Conclusions: Full-dose vancomycin increases the likelihood of achieving PD targets like AUC/MIC in AKI patients. Larger studies are warranted to confirm these findings.