Endothelial, renal and hepatic variables in wistar rats treated with Vancomycin

Abstract

Vancomycin (VCM) is indicated in combat against Gram-positive infections, but it is not considered a first-choice drug because of its adverse effects. It is believed that oxidative stress is the primary mechanism of endothelial injury and the consequent VCM toxicity, which varies from phlebitis to nephrotoxicity. Moreover, dose recommendations, dilution, rates and types of infusion are still controversial. The aim of this study was to determine the effect of different VCM dilutions in endothelial, liver and kidney injuries by biochemical parameters and histopathological analysis. Wistar rats were randomly divided into six groups and subjected to femoral vein cannulation for drug administration. Control groups received 0.9 ml of saline and the others received VCM (10mg/Kg/day) at dilutions of 5.0 and 10.0 mg/mL for 3 and 7 days. Homocysteine, hs-CRP, AST, ALT, GGT, urea, creatinine, lycopene, alpha-tocopherol, beta-carotene and retinol were analyzed. Kidney, liver and cannulated femoral vein fragments were collected.This study showed alterations in ALT which featured hepatotoxicity. However, drug dilutions were not able to show changes in other biochemical parameters. In contrast, kidney and endothelium pathological changes were observed. More studies are needed to characterize VCM induced kidney and endothelium toxicity and biochemical markers able to show such morphological modifications.

Large Cohort Study of Central Venous Catheter Thrombosis during Intravenous Antibiotic Therapy

“…Fifteen out of 16 patients developing CRT were treated with high-dose continuous intravenous vancomycin. Even though the venotoxicity of vancomycin has been known for a long time (23)(24)(25), publications on vancomycinassociated CRT are rare. A case-control study, including 400 patients with a peripherally inserted central catheter (PICC) concluded that the infusion of antibiotics, particularly vancomycin, was a risk factor for venous thrombosis (5).…”

Eremomycin Picolylamides and Their Cationic Lipoglycopeptides: Synthesis and Antimicrobial Properties

“…Основным препаратом выбора для лечения тяжелых, устойчивых к антибиотикам бактериальных инфекций, прежде всего, ассоциированных с метициллин-резистентным стафилококком (MRSA), до сих пор остается гликопептидный антибиотик ванкомицин (1). [3] Однако широкое применение ванкомицина в течение последних десятилетий привело к распространению устойчивых штаммов энтерококков и стафилококков (VRE и GISA). Кроме того, недостатками ванкомицина являются его нефро-и ототоксичность, а также способность вызывать псевдоаллергические реакции, связанные с высвобождением гистамина.…”

High‐Performance Liquid Chromatography Method for Rich Pharmacokinetic Sampling Schemes in Translational Rat Toxicity Models With Vancomycin

“…Complicating the understanding, clinical dosing results in homogenous exposure profiles, and patient comorbidities impact the ability to identify the true toxicodynamic relationship. Thus, there is a renewed interest in controlled laboratory experiments (e.g., animal models) to best discern mechanistic links between pharmacokinetic (PK) exposures and toxicodynamic outcomes . Additionally, there are limited data on toxicity of vancomycin in utero , and these analyses were performed before sensitive biomarkers of vancomycin toxicity were available for study.…”

“…Thus, there is a renewed interest in controlled laboratory experiments (e.g., animal models) to best discern mechanistic links between pharmacokinetic (PK) exposures and toxicodynamic outcomes. [8][9][10][11][12] Additionally, there are limited data on toxicity of vancomycin in utero, 13 and these analyses were performed before sensitive biomarkers of vancomycin toxicity were available for study.…”