Vancomycin-induced Nephrotoxicity Research Articles

Effects of tadalafil on vancomycin-induced nephrotoxicity in rats

Effects of tadalafil on vancomycin-induced nephrotoxicity in rats

Nephroprotective Effect of Vinpocetine against Vancomycin-induced Nephrotoxicity in Rats

Background: The kidney is a vital organ for the body and is vulnerable to drug toxicity. For methicillin-resistant Staphylococcus aureus, vancomycin is the antibiotic of choice. It has been accompanied by nephrotoxicity, which restricts its use. Numerous studies have reported that nephrotoxicity was linked to oxidative stress and inflammatory response. Vinpocetine is a derivative of vincamine alkaloid used to treat some neurological disorders and has antioxidant and anti-inflammatory effects. The objective of the study: To evaluate the nephroprotective effect of vinpocetine against vancomycin-induced nephrotoxicity in rats. Methods: Twenty-four albino male rats were randomly selected and divided into three groups (n = 8): (1) Normal group: apparently healthy rats. (2) Induction group: treated with vancomycin (200mg/kg) twice daily intraperitoneally for 14 days. (3) Vinpocetine group: As the group (2) and treated with vinpocetine (2.5mg/kg) twice daily orally, an hour before vancomycin administration. Results: Vinpocetine group demonstrated a significant decrease in urea, creatinine, and cystatin C serum levels compared to the induction group. Also, it showed a significant reduction in the renal tissue level of malondialdehyde and a significant elevation in the renal tissue level of glutathione as compared to the induction group. Furthermore, the vinpocetine group showed a significant decrease in the renal tissue levels of tumour necrosis factor-alpha and neutrophil gelatinase-associated lipocalin. Histologically, all rats in vinpocetine group showed a significantly reduced level of renal tissue damage. Conclusion: The present study shows that vinpocetine exhibited nephroprotective due to its antioxidant and anti-inflammatory effects. Keywords: Nephrotoxicity, Oxidative stress, Vancomycin, Vinpocetine.

Renogrit attenuates Vancomycin-induced nephrotoxicity in human renal spheroids and in Sprague-Dawley rats by regulating kidney injury biomarkers and creatinine/urea clearance

Vancomycin, is widely used against methicillin-resistant bacterial infections. However, Vancomycin accumulation causes nephrotoxicity which leads to an impairment in the filtration mechanisms of kidney. Traditional herbal medicines hold potential for treatment of drug-induced nephrotoxicity. Herein, we investigated protective properties of plant-based medicine Renogrit against Vancomycin-induced kidney injury. Phytometabolite analysis of Renogrit was performed by UHPLC. Spheroids formed from human proximal tubular cell (HK-2) were used for in vitro evaluation of Vancomycin-induced alterations in cell viability, P-gp functionality, NAG, KIM-1 levels, and mRNA expression of NGAL and MMP-7. The in vivo efficacy of Renogrit against Vancomycin-induced nephrotoxicity was further evaluated in Sprague-Dawley (SD) rats by measurement of BUN, serum creatinine, and their respective clearances. Moreover, eGFR, kidney-to-body weight ratio, GSH/GSSG ratio, KIM-1, NAG levels and mRNA expression of KIM-1 and osteopontin were also analyzed. Changes in histopathology of kidney and hematological parameters were also observed. Renogrit treatment led to an increase in cell viability, normalization of P-gp functionality, decrease in levels of NAG, KIM-1, and reduction in mRNA expression of NGAL and MMP-7. In Vancomycin-challenged SD rats, Renogrit treatment normalized altered kidney functions, histological, and hematological parameters. Our findings revealed that Renogrit holds a clinico-therapeutic potential for alleviating Vancomycin-associated nephrotoxicity.

Analysis of kidney proteomes to identify biological pathways associated with vancomycin-induced nephrotoxicity in mice by tandem mass tag-labeled quantitative and parallel reaction monitoring phosphoproteomics.

Vancomycin (VCM)-induced nephrotoxicity impedes its treatment applications. Thus, it is important to clarify the relevant mechanism. This study investigated phosphoprotein changes attributable to the VCM nephrotoxicity mechanisms. Biochemical, pathological and phosphoproteomic analyses based on C57BL/6 mice were performed to explore the mechanisms.VCM-treated mice showed increased levels of blood urea nitrogen and creatinine, and signs of acute tubular necrotic lesions. Phosphoproteomic profiling identified 3025 differentially phosphorylated phosphopeptides between the model and control group. Gene Ontology enrichment analysis demonstrated that Molecular Function "oxidoreductase activity" and Cellular Component "peroxisome" were markedly enriched. KEGG pathway analysis identified an enrichment in peroxisome pathway and PPAR (peroxisome proliferator-activated receptor) signaling pathways. Parallel reaction monitoring analysis revealed a significant downregulation of CAT, SOD-1, AGPS, DHRS4, and EHHADH at phosphorylation level by VCM. Notably, the phosphorylation of ACO, AMACR, and SCPX was downregulated by VCM, which are the fatty acid β-oxidation-related proteins involved in PPAR signaling pathways. The phosphorylated PEX5 involved in peroxisome biogenesis was upregulated by VCM. Collectively, these findings indicated that VCM-induced nephrotoxicity is closely associated with peroxisome pathway and PPAR signaling pathways. The current study provides important insight into the mechanisms of VCM nephrotoxicity and will aid in the development of preventive and therapeutic strategies against this nephropathy.

Risk Factor Analysis of Vancomycin-Induced Nephrotoxicity in Paediatric Patients Aged 0-1 Year Using Japanese Medical Database.

Vancomycin (VCM)-induced nephrotoxicity (VIN) is a major side effect in paediatric patients. However, most studies are limited to patients aged 0-18 years. We evaluated the risk factors of VIN in patients aged 0-1 year using Japanese electronic medical record database. We used RWD database which was contained electronic medical records and claims data of approximately 20 million people from 160 medical institutions. We targeted hospitalized patients who were administered VCM between June 2000 and December 2020. VIN was defined by two criteria: Criterion 1 was an increase in serum creatinine (Scr) ≥ 0.5 mg/dL or 50% during VCM treatment period compared to the Scr baseline; and criterion 2 was an increase in Scr ≥50% within seven days or Scr ≥0.3 mg/dL within two days during VCM treatment. The risk factors of VIN were evaluated using multivariate logistic regression analysis. We analysed 446 patients; patients with VIN in Criteria 1 and 2 were 33 and 58, respectively. In Criterion 1, multivariate logistic regression analysis identified four independent factors with p-value <0.05 (VCM concentration ≥20 mg/L, amphotericin B (AMPH-B), piperacillin-tazobactam (TAZ/PIPC), and vasopressor drugs). In Criterion 2, multivariate logistic regression analysis identified concomitant use of vasopressor drugs with p-value <0.05. Therefore, concomitant use of vasopressor drugs was suggested to affect the risk of VIN in patients aged 0-1 year. The findings may help in developing estimation models to assess the risk of VIN in paediatric patients.

Pharmacokinetic and Biomarker Quantification Studies on Vancomycin-Loaded PEGylated Liposomes and Its Potential to Reduce Vancomycin-Induced Kidney Injury: A Rat Study.

Vancomycin is a commonly used antibiotic in hospital settings, especially against Methicillin-resistant staphylococcus aureus (MRSA). One of the major adverse events of vancomycin use in adults is kidney injury. The drug concentration, specifically the area under the concentration curve, predicts kidney injury in adults receiving vancomycin. To attempt to reduce vancomycin-induced nephrotoxicity, we have successfully encapsulated vancomycin in polyethylene glycol-coated liposomes (PEG-VANCO-lipo). We have previously carried out in vitro cytotoxicity studies on kidney cells using PEG-VANCO-lipo and found it to be minimally toxic compared to the standard vancomycin. In this study, we have dosed male adult rats with PEG-VANCO-lipo or vancomycin HCl and compared plasma vancomycin concentrations and KIM-1 as an injury biomarker in rat urine. Male Sprague Dawley rats (350 ± 10 g) were administered vancomycin (n = 6) or PEG-VANCO-lipo (n = 6) 150 mg/kg/day for three days using an IV infusion in the left jugular vein catheter. Blood was collected for plasma at 15, 30, 60, 120, 240, and 1440 min after the first and the last IV dose. Urine was collected 0-2, 2-4, 4-8, and 8-24 h after the first and the last IV infusions using metabolic cages. The animals were observed for three days after the last compound administration. Vancomycin was quantified in plasma by LC-MS/MS. Urinary KIM-1 analysis was done by using an ELISA kit. Three days after the last dose, under terminal anesthesia with IP ketamine (65-100 mg/kg) and xylazine (7-10 mg/kg), rats were euthanized. Vancomycin urine and kidney concentrations and KIM-1 were lower on day three in the PEG-Vanco-lipo group compared to the vancomycin group (p < 0.05, ANOVA and/or t-test). There was a significant reduction in plasma vancomycin concentration on day one and day three (p < 0.05, t-test) in the vancomycin group compared to the PEG-VANCO-lipo group. Vancomycin-loaded PEGylated liposomes resulted in lower levels of kidney injury, as noted by a decrease in KIM-1 values. Moreover, longer circulation in plasma with increased concentration in plasma as opposed to the kidney was observed with the PEG-VANCO-lipo group. The results indicate the high potential of PEG-VANCO-lipo in decreasing the nephrotoxicity of vancomycin clinically.

The influence of vancomycin on renal functions, the predictors and associated factors for nephrotoxicity.

Vancomycin has been widely used in the last six decades to treat methicillin-resistant S. aureus (MRSA) and other resistant gram-positive infections. The risk of vancomycin toxicity increases with the utilization of higher doses while treating the resistant form of bacterial infections. Nephrotoxicity is one of the major complications reported to be a hinderance in the prognosis of vancomycin therapy. This hospital-based study aimed to highlight the influence of vancomycin on renal function with special emphasis on identifying the predictors and augmenting factors for nephrotoxicity. A cross-sectional, unicentric, hospital-based study was conducted at King Fahad Specialist Hospital (KFSH) in Qassim region in Saudi Arabia (KSA). It included 319 hospitalized patients who received vancomycin at intermittent doses (15 to 30 mg/kg IV per day) based on the diseased state. Data regarding vancomycin dose, frequency, duration and data of renal function tests and type of admission were analysed to evaluate their influence on the renal function using parameters such as blood urea, serum creatinine levels and creatinine clearance. One-way ANOVA and Spearman correlation test were used in the analysis of data. Both male and female patients treated with vancomycin had significantly (p<0.05) elevated blood urea and serum creatinine levels compared to baseline levels while creatinine clearance was non-significantly varied. Increasing age, increasing body weight, higher vancomycin dose and trough levels, increased vancomycin frequency and duration, critically ill patients and site of infection were factors associated with significant (p<0.05) increases in blood urea and serum creatinine levels with reduction in creatinine clearance. Data suggested that vancomycin treatment reduced the renal function in patients and indicated its association with several predictors and confounding factors. The findings of the study might assist in identifying the patients under risk from the vancomycin-induced nephrotoxicity and in designing the preventive strategies to reduce such complications.

Nephroprotective potential of Polyalthia longifolia roots against vancomycin-induced renal toxicity in experimental animals.

This study was done to investigate the possible nephroprotective effect of an ethanolic root extract of Polyalthia Longifolia (PL) on vancomycin-induced nephrotoxicity using curative and protective models. Vancomycin (150mg/kg, intravenous) was given to healthy Wistar albino rats in the curative model before the start of treatment, whereas the protective group received vancomycin at the conclusion of the 10-day treatment procedure. Animals were divided into six groups for both models; group I served as the normal control, while groups II, III, IV, V, and VI were kept as toxic control, standard (selenium, 6mg/kg), LDPL (low dose of PL 200mg/kg), HDPL (high dose of PL 400mg/kg), and HDPL + selenium (interactive) groups, respectively. Renal biomarkers [(uric acid, creatinine, blood urea nitrogen (BUN), serum proteins], and blood electrolyte levels were measured for all tested groups. When compared to the vancomycin group, the HDPL significantly (p < 0.01) showed greater effectiveness in lowering the BUN, potassium, and calcium levels. Additionally, in the curative model, there was a significant (p < 0.05) decrease in the blood levels of uric acid, creatinine, BUN, potassium, and calcium in the animals who received the combination of selenium and HDPL. Both LDPL and HDPL did not provide any distinguishable effect in the protective model, but groups that received HDPL with selenium did provide detectable protection by significantly lowering their levels of uric acid, BUN, serum potassium, and total serum protein in comparison to the vancomycin control group. These findings indicate that, whether administered before or after renal damage is induced, the Polyalthia longifolia root extract provided only modest protection to nephrons, which require selenium support to prevent vancomycin-induced kidney damage.

Relationship between vancomycin-induced nephrotoxicity and vancomycin trough concentration in older adults: A retrospective observational study.

The objective of the study is to investigate the risk factors of vancomycin-induced renal toxicity in older adults, especially in those with chronic kidney disease (CKD) Stages 3-5. In this retrospective observational study, serum vancomycin trough concentrations (VTCs) in patients aged g65 years treated with vancomycin were analyzed, and independent risk factors of vancomycin-induced nephrotoxicity (VIN) were determined by logistic regression analysis. In total, 321 patients were included in this study. Serum VTC was an independent risk factor for vancomycin-induced renal toxicity in total cohort (odds ratio [OR], 1.07; P = 0.004) as well as in the cohort with CKD Stages 3-5 (OR, 1.09; P = 0.010). A daily dose of vancomycin and Charlson comorbidity index was an independent risk factor for vancomycin-induced renal toxicity in total cohort (OR, 3.63; P = 0.006) and in the cohort with CKD Stage 3-5 (OR, 1.83; P = 0.002), respectively. In older adults with CKD Stages 3a and 3b-5, the VTCs associated with higher risk for vancomycin-induced renal toxicity were 21.5 mg/L and 16.5 mg/L, respectively. In older adults, serum VTC is an independent risk factor for VIN. VTCs over 21.5 mg/L and 16.5 mg/L are associated with increased risk of VIN in this population with CKD Stage 3a and 3b-5, respectively.

Could melatonin prevent Vancomycin-induced nephrotoxicity in critically ill patients? A randomized, double-blinded controlled trial.

Previous research showed some clinical benefits regarding the nephroprotective effect of melatonin. So, this study aimed to evaluate the beneficial effect of oral melatonin on preventing acute kidney injury (AKI) in patients who received vancomycin therapy in the intensive care unit (ICU). We performed a randomized, double-blinded, placebo-controlled pilot study in an academic hospital. Adult patients admitted to the ICU who received vancomycin with normal gastrointestinal and kidney function were randomized into treatment or placebo groups. After that, enrolled patients received a tablet of melatonin (3 mg) or placebo twice daily for seven consecutive days. The occurrence of AKI was assessed by RIFLE criteria (by measurement of serum creatinine (SCr)) and plasma neutrophil gelatinase-associated lipocalin (NGAL) concentration. Moreover, other data related to renal functions and SOFA were also compared between groups. A total of 90 patients were included in the study, while 21patients in the placebo group and 20 in the intervention group completed the study. There were no significant differences between groups regarding baseline SCr, BUN, urine output, NGAL, SOFA, and glomerular filtration rate (GFR). Our results showed that these differences remained insignificant after a 7-day follow-up between groups. However, the incidence of AKI was significantly lower in the melatonin group based on the NGAL cutoff (> 150 ng/mL). We detected a significant decrease in vancomycin-induced nephrotoxicity incidence in patients receiving melatonin compared to placebo. However, more clinical trials in a larger population were required to confirm this result.

588. A Safety analysis of High Dose Intrawound Vancomycin in Arthroplasty

Abstract Background There is a paucity of data to support the efficacy and safety of placing vancomycin powder into and around the joint in total hip arthroplasty (THA), total knee arthroplasty (TKA), and shoulder arthroplasty (SA). Methods This was a retrospective chart review of patients undergoing THA, TKA, or SA who received intrawound (IW) vancomycin powder placed into and around the joint with a vancomycin impregnated bone cement spacer (VIBCS) compared to patients who received a VIBCS alone (usual care). Results There were 24 patients who met inclusion criteria. Of the 14 patients who received IW vancomycin, the median dose (Range) was 5g (4-10). While there were no statistically significant differences in baseline demographics, those who received IW vancomycin were more likely to experience vancomycin induced nephrotoxicity (VIN) compared to those who received usual care (42.9% vs. 0%, P=0.02) (Table 1). Conclusion Our experience with IW vancomycin at a median dose of 5g in combination with VIBCS was associated with an increased risk of nephrotoxicity in our patients. Therefore, re-evaluation of the use of IW vancomycin at these doses is warranted. Disclosures All Authors: No reported disclosures.

Carvacrol mitigates vancomycin-induced nephrotoxicity via regulation of IkBα/p38MAPK and Keap1/Nrf2 signaling pathways: an experimental study with in silico evidence.

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Role of Vancomycin Area Under the Curve Trapezoidal Dosing in Prevention of Nephrotoxicity as Compared with Traditional Trough-based Dosing

Published on: October 2022Journal of Young Pharmacists, 2022; 14(4):408-411Original Article | doi:10.5530/jyp.2022.14.82 Authors:Robert J Kranz*, Erin M LockardDepartment of Pharmacy, MercyOne Medical Center, 3421 W 9th Street, Waterloo, IA 50702, USA. Abstract:Background: Vancomycin is a fundamental treatment for resistant grampositive infections and is implicated in vancomycin-induced-nephrotoxicity (VIN) at high concentrations. Troughs greater than 18 mcg/ml are associated with a 4-fold increase in nephrotoxicity. Additionally, Area Under the Curve/ Minimum Inhibitory Concentration (AUC/MIC) levels over 600 mg*h/L are implicated in VIN. It is proposed that trapezoidal AUC/MIC dosing strategies reduce VIN instances. Materials and Methods: Patients greater than 18 years of age who received 72 hr of vancomycin therapy for a non-skin or soft-tissue or urinary indication were included in this retrospective cohort study. The primary endpoint was rate of nephrotoxicity based on the Acute Kidney Injury Network (AKIN) criteria for those patients who suffered an increase in serum creatinine of 0.3 mg/dl or greater after 48 hr of vancomycin therapy. The secondary endpoints were mean 24-hr vancomycin daily doses and instances of trough excursions above 18 mcg/ mL between groups. Forty patients met inclusion criteria for the AUC/MIC arm while seventy-nine met inclusion to the trough arm. Results: Rates of nephrotoxicity in the trough versus AUC/MIC were 36 patients (30.3%) and 3 patients (7.5%) respectively with a p<0.001. AUC/MIC based dosing was associated with decreased rates of nephrotoxicity and decreased rates of trough excursions above 18 mcg/ml. Conclusion: The AUC/MIC dosing strategy was associated with lower rates of VIN compared with trough based dosing.Keywords: Acute Kidney Injury, Creatinine Clearance, Vancomycin.

Effectiveness of melatonin in preventing vancomycin-induced nephrotoxicity: an experimental study

Purpose: The aim of the study explores probable toxic effects of vancomycin on kidney and analysis of the probable protective effects of melatonin.&#x0D; Materials and Methods: In this study, rats were randomly divided into 4 groups: the control group; the melatonin (10 mg/kg/day) group; the vancomycin-treated (200 mg/kg) group; and the vancomycin (200 mg/kg) + melatonin (10 mg/kg/day) group. Rats in the treatment group were given two doses of vancomycin a day with an interval of seven consecutive days and melatonin (10 mg/kg/day) once daily for seven consecutive days. The experiment was continued for 15 days. In each group, seven rats were grouped together. 15 days after the experiment, the rats were sacrificed under anesthesia and among all groups. Kidney tissues were collected and processed for further TNF- expression analysis, as well as histological analyses such as hematoxylin and eosin (H&amp;E), Masson's tricrom, and Periodic acid schiff (PAS) staining to assess pathological severity. In addition, a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to evaluate apoptosis.&#x0D; Results: While vancomycin upregulated TNF-α expression, melatonin reduced levels of TNF-α immunoreactivity intensity and clearly improved pathological severity in rat kidneys. Further, melatonin significantly inhibited vancomycin-induced TUNEL-positive cell numbers. &#x0D; Conclusion: Melatonin has protective activity against vancomycin-induced pro-inflammatory and proapoptotic effects in kidneys during organ preservation time and improves kidney function.

Bibliometric and visual analysis of nephrotoxicity research worldwide.

Background: Nephrotoxicity of drugs contributes to acute kidney injury with high mortality and morbidity, which crucially limits the application and development of drugs. Although many publications on nephrotoxicity have been conducted globally, there needs to be a scientometric study to systematically analyze the intellectual landscape and frontiers research trends in the future. Methods: Publications on nephrotoxicity from 2011 to 2021 were collected to perform bibliometric visualization using VOSviewer, CiteSpace, and Scimago Graphica software based on the Web of Science Core Collection. Results: A total of 9,342 documents were analyzed, which were primarily published in the United States (1,861), China (1,724), and Egypt (701). For institutions, King Saud University (166) had the most publications; Food and Chemical Toxicology, PLOS One, and Antimicrobial Agents and Chemotherapy were productive journals, primarily concentrating on the mechanisms of nephrotoxicity and renoprotective in cisplatin and antibiotics, especially in oxidative stress. Burst detection suggested that cisplatin, piperacillin-tazobactam, vancomycin-induced nephrotoxicity, antioxidants, and new biomaterials are frontiers of research. Conclusion: This study first provides an updated perspective on nephrotoxicity and renoprotective strategies and mechanisms. This perspective may benefit researchers in choosing suitable journals and collaborators and assisting them in the deep understanding of the nephrotoxicity and renoprotective hotspots and frontiers.

M059 Evaluation of 10 serum biomarkers in vancomycin-induced nephrotoxicity

M059 Evaluation of 10 serum biomarkers in vancomycin-induced nephrotoxicity

Vancomycin Therapeutic Drug Monitoring (TDM) and Its Association with Clinical Outcomes: A Retrospective Cohort

BackgroundTherapeutic drug monitoring (TDM) has proven effectiveness in maintaining efficacy and reducing toxicities associated with vancomycin. A trough level of (15–20 mg/L) for MRSA serious infections is recommended. Therapeutic failure is of concern due to suboptimal routine vancomycin utilization in clinical practice. This study aims to identify factors of vancomycin TDM practice potentially associated with vancomycin-induced nephrotoxicity and therapeutic failure measured by the need to restart vancomycin therapy within 28-days and all-cause mortality in a tertiary hospital in Oman. MethodsA single-center retrospective cohort was conducted in a tertiary care hospital that included all adult patients aged ≥ 18 years treated with IV vancomycin for> 72 h. ResultsVancomycin therapeutic level was not achieved in 16.8% of the patients, and 47.5% had high levels (>20 mg/L). Vancomycin-induced nephrotoxicity occurred in 31.7% of the patients, it was restarted within 28-days in 18.8% of the patient, and 25.2% of the patients died during the same hospitalization. Univariate analysis showed old age (p < 0.01), higher baseline creatinine reading (p = 0.03), high vancomycin level (p = 0.03), and vancomycin-induced nephrotoxicity (p < 0.01) were associated with increased all-cause mortality. Multivariate analysis identified overweight and vancomycin-induced nephrotoxicity were independent factors associated with increased all-cause mortality (OR:1.04; p = 0.043; 95% CI 1.00–1.08) and (OR:1.96; p = 0.049; 95% CI 1.00–21.61) respectively. ConclusionFailure to achieve the recommended therapeutic vancomycin level (15–20 mg/L) is common in clinical practice and associated with poor health outcomes; hence, appropriate TDM practice is an essential exercise to improve efficacy, prevent failure and reduce serious toxicities associated with vancomycin therapy.

Renoprotective effects of Adansonia digitata leaf extract on renal function and histopathological changes in vancomycin-induced nephrotoxicity in Wistar rats

Renoprotective effects of Adansonia digitata leaf extract on renal function and histopathological changes in vancomycin-induced nephrotoxicity in Wistar rats

Using Japanese big data to investigate novel factors and their high-risk combinations that affect vancomycin-induced nephrotoxicity.

Several factors related to vancomycin-induced nephrotoxicity (VIN) have not yet been clarified. In the present study, we used Japanese big data to investigate novel factors and their high-risk combinations that influence VIN. We employed a large Japanese electronic medical record database and included patients who had been administered intravenous vancomycin between June 2000 and December 2020. VIN was defined as an increase in serum creatinine ≥0.5mg/dL or 1.5-fold higher than the baseline. The outcomes were: (1) factors affecting VIN that were identified using multiple logistic regression analysis, and (2) combinations of factors that affect the risk of VIN according to a decision tree analysis, which is a typical machine learning method. Of the 7306 patients that were enrolled, VIN occurred in 14.2% of them (1035). A multivariate analysis extracted 22 variables as independent factors. Concomitant ramelteon use (odds ratio 0.701, 95% confidence interval 0.512-0.959), ward pharmacy service (0.741, 0.638-0.861), duration of VCM < 7days (0.748, 0.623-0.899) and trough concentrations 10-15 mg/L (0.668, 0.556-0.802) reduce the risk of VIN. Meanwhile, concomitant piperacillin-tazobactam use (2.056, 1.754-2.409) and piperacillin use (2.868, 1.298-6.338) increase the risk. The decision tree analysis showed that a combination of vancomycin trough concentrations ≥20 mg/L and concomitant piperacillin-tazobactam use was associated with the highest risk. We revealed that the concomitant ramelteon use and ward pharmacy service may decrease the risk of VIN, while the concomitant use of not only piperacillin-tazobactam but also piperacillin may increase the risk.

Berberis aristata reduces vancomycin-induced nephrotoxicity by down-regulation of cell proliferation markers

IntroductionVancomycin is used to treat bacterial infections but there is a risk of nephrotoxicity associated with it. Oxidative stress is the possible cause of this nephrotoxicity. Plant extracts have long been used in fighting oxidative stress and have proved quite useful. The present study investigated the treatment potential of Berberis aristata root extract against nephrotoxicity induced by vancomycin. MethodsB. aristata was collected from Chikar Valley, Azad Kashmir, identified, and later analyzed by High-pressure liquid chromatography (HPLC). Vero cells were used to determine the effects of B. aristata extract. For the determination of apoptotic and anti-inflammatory effects cells were divided into three major groups; Control, Vancomycin, and Treated. The control groups were either left untreated or treated with 0.1% DMSO. Vancomycin group was treated with 0.6 mg/mL, 3 mg/mL, and 6 mg/mL of vancomycin, while treated groups were treated with (100 µg/mL, 200 µg/mL, 400 µg/mL) along with various vancomycin (0.6 mg/mL, 3 mg/mL, and 6 mg/mL) concentrations. The mRNA expression of antioxidant and proliferative markers (p53, p21, Cas 4, Cas 5, Cas 9, and Cyt-c) was assessed by qPCR. ResultsHPLC chromatogram indicated the presence of berberine component by comparing the peaks at retention time. The mRNA expression of all selected markers was found to be upregulated in the vancomycin group with a decrease of expression in treated groups, indicating the recovery from vancomycin-induced damage to kidney cells. ConclusionB. aristata extract can be used along with vancomycin treatment to minimize its toxicity.