Changes of renal transporters in the kinetic process of VCM-induced nephrotoxicity in mice. It remains uncertain, however, to what extent vancomycin is directly responsible, as numerous potential risk factors for acute kidney injury frequently coexist. Collection and assembly of data: I.B., V.P. IntHout J, Ioannidis JPA, Rovers MM et al. The https:// ensures that you are connecting to the All rights reserved. Nephrol. Nonetheless, there remained a variety of indications treated with vancomycin in this time frame, notably skin and soft tissue infections, pneumonia, and bacteremia. Evaluation of Vancomycin TDM Strategies: Prediction and Prevention of Kidney Injuries Based on Vancomycin TDM Results. Furthermore, data regarding ICU patients were sparse, resulting in wide credibility intervals and thus raising concerns about the direct applicability of the present outcomes in this specific population. Before The concept that piperacillin-tazobactam exerts some sort of weird, selective nephrotoxicity solely in the presence of vancomycin is a myth. and transmitted securely. The role of urinary biomarkers in AKI related to vancomycin is unknown.Objective: The aim of this study was to evaluate the role of urinary IL-18, KIM-1, NGAL, TIMP-2, and IGFBP7 as diagnostic and prognostic . Li H, Yang Q, Gui M, et al. The patient was sent to the emergency department for an acutely elevated creatinine of 4.0 mg/dL. This is an illustration of the illusory truth effect, a phenomenon whereby repeated information is perceived as more truthful than new information. Egger M, Davey Smith G, Schneider M et al. The exact mechanism of vancomycin-induced nephrotoxicity is not completely understood; however, current data suggest that use of the antibiotic causes oxidative effects on the proximal renal tubule resulting in renal tubular ischemia. This link was also found in ICU patients and was independent of AKI definition criteria. Luther MK, Timbrook TT, Caffrey AR, Dosa D, Lodise TP, LaPlante KL. The current evidence for vancomycin-induced AKI (VIAKI . The patient's symptoms continued to improve. Impurities in early formulations, often referred to as "Mississippi mud," rendered the product more toxic than the purified formulation that is in use today. ODonnell JN, Rhodes NJ, Miglis CM et al. A literature review. Vancomycin-associated tubular cast (VTC) was recently described and may represent a novel cause of vancomycin nephrotoxicity. She was started on intravenous daptomycin and meropenem, with plans to switch to oral antibiotics at outpatient follow-up after discharge. This primed them to be ready to believe any adverse effects from this combination. Epub 2021 Mar 18. 2023 Apr 11;120(15):e2208737120. The present meta-analysis was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.17 The protocol of the study is available online (dx.doi.org/10.17504/protocols.io.bcctiswn). A random-effects model was used to provide estimates of SMD and 95% CI, while the KnappHartung approach was implemented to provide small-sample adjustments.24 Heterogeneity was assessed by the between-study variance (2) and its impact on the outcome was evaluated with the 95% prediction interval (PI); these reflect the effects to be expected in future populations. The vancomycin monitoring guidelines define nephrotoxicity as multiple increases of 0.5 mg/dl or 50% increase in creatinine over two to three consecutive measurements in the absence of another. 2006 ]. However, trough levels have been treated only as a binary variable with varying thresholds, which, along with the moderate number of included studies, precludes the drawing of safe conclusions to guide clinical decisions. In particular, 52 studies adopted a retrospective design, while 8 studies were prospective cohorts and 1 study represented a post hoc analysis of a randomized controlled trial. Renal biopsy revealed acute tubulointerstitial nephritis with severe acute tubular injury. Write a review. As a result, future research should focus on the stratification of patients using multivariate predictive models in order to identify those at high risk of renal impairment and offer individualized therapeutic drug monitoring, aiming to achieve treatment success without jeopardizing kidney function. Diagnostic accuracy analysis demonstrated that initial trough levels at the cut-off of 15mg/L predicted the occurrence of AKI with a sensitivity of 62.6% (95% CI: 55.669.2) and a specificity of 65.5% (95% CI: 58.971.6), while applying a threshold of 20mg/L resulted in a sensitivity of 42.9% (95% CI: 3452.2) and a specificity of 82.5% (95% CI: 73.988.8). This article is intended to serve as a practical review of vancomycin-associated nephrotoxicity, including historical context, risk factors, and common methods to evaluate and define renal dysfunction. Shapeshifting bullvalene-linked vancomycin dimers as effective antibiotics against multidrug-resistant gram-positive bacteria. Watkins R, Deresinski S. Increasing Evidence of the Nephrotoxicity of Piperacillin/Tazobactam and Vancomycin Combination Therapy-What Is the Clinician to Do? Vancomycin MICs for many pathogens have been increasing during the past decade. Moreover, the association of initial trough levels with renal toxicity risk is explored by assessing their exact accuracy as predictive markers of AKI. The pathophysiology of vancomycin nephrotoxicity is considered. The patient was slightly somnolent. 1. In fact, blocking organic anion transporters has. Starting around 2011, retrospective studies emerged showing that patients treated with vancomycin plus piperacillin-tazobactam had increased rates of acute kidney injury compared to patients treated with vancomycin plus other beta-lactams. More specifically, 11 studies3444 were excluded after reading the full text. Fifty wrongs dont make a right. We review the pharmacokinetics/pharmacodynamics of vancomycin metabolism. Vancomycin earned notoriety for its tendency to cause nephrotoxicity shortly after it was introduced into practice, though the impurities responsible for historically significant rates of nephrotox. Especially pay close attention to vancomycin levels in patients who are developing renal failure vancomycin levels may progressively rise, causing an exacerbation of renal failure in a vicious spiral. & Kollef, M.H. For example: So, many practitioners have slowly come to loathe the combination of vancomycin and piperacillin-tazobactam. Disclaimer. Surely, we think, such myths wouldnt arise today not in our shiny, interconnected, science-based, hyper-argumentative medical world. See. Sensitivity for S. aureus based on vancomycin MIC is as follows: However, infections due to S. aureus with a vancomycin MIC 2 mcg/mL ( 1.4 micromol/L) may respond suboptimally to standard dosing even when the daily AUC is 400 to 600, so the threshold for . The pathophysiology of vancomycin nephrotoxicity is considered. At the emergency department, her blood pressure was 155/63 mm Hg; pulse, 70 beats/minute; temperature, 97.3F; and respiratory rate, 19 breaths/minute. 2021;52(2):85-97. doi: 10.1159/000513742. It should also be stated that paediatric and dialysis patients were excluded from this meta-analysis and thus the findings cannot be generalized to these patient categories. These studies are severely limited by their myopic focus on creatinine, while ignoring other endpoints. In critically ill patients, anti-anaerobic antibiotics increase risk of adverse clinical outcomes (ersjournals.com). Regardless, there was a gradual and broad acceptance of the concept that vancomycin plus piperacillin-tazobactam is nephrotoxic. , Divine, G. , Vazquez, J.A. She had been receiving scheduled intravenous vancomycin infusions without having her vancomycin trough levels monitored at the nursing facility. Exclusion criteria included the following: paediatric population, outpatient setting, renal replacement therapy, kidney transplantation and cystic fibrosis. Higgins J, Thomas J, Chandler J et al. Federal government websites often end in .gov or .mil. h/L is recommended in order to ensure vancomycin effectiveness.11,12 However, due to the complexity of AUC calculation, steady-state trough levels are widely measured as a surrogate marker of achieving the desired AUC/MIC ratio, with levels between 15 and 20mg/L representing the target in most complicated infections.13 Nonetheless, growing evidence exists to challenge this recommendation, as trough levels greater than 15mg/L have been shown to correlate more strongly with nephrotoxicity than with clinical success.14. Vancomycin is valued for its effectiveness in the treatment of severe infections caused by methicillin-resistant Staphylococcus aureus. The literature search was performed using the Medline, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL) and Clinicaltrials.gov databases. The .gov means its official. Online Medical Education on Emergency Department (ED) Critical Care, Trauma, and Resuscitation. This study demonstrates that piperacillin-tazobactam elevated creatinine without causing true kidney injury or affecting blood urea nitrogen levels. The outcomes of the present meta-analysis support the hypothesis that increasing vancomycin trough levels are linked to a higher risk of AKI development, raising concerns about the safety of strategies aiming for the attainment of high concentrations, especially >15mg/L. The concentration-independent effect of monoexponential and biexponential decay in vancomycin concentrations on the killing of, Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists, Association between the AUC0-24/MIC ratio of vancomycin and its clinical effectiveness: a systematic review and meta-analysis, Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia, The safety and efficacy of high versus low vancomycin trough levels in the treatment of patients with infections caused by methicillin-resistant, High versus low vancomycin serum trough regimen for Gram-positive infections: a meta-analysis, The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration, KDIGO clinical practice guidelines for acute kidney injury, Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury, Acute renal failuredefinition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group, Effectiveness and efficiency of search methods in systematic reviews of complex evidence: audit of primary sources, ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions, Improved tests for a random effects meta-regression with a single covariate, Plea for routinely presenting prediction intervals in meta-analysis, Bias in meta-analysis detected by a simple, graphical test, Operating characteristics of a rank correlation test for publication bias, Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis, One-stage doseresponse meta-analysis for aggregated data, A hierarchical regression approach to meta-analysis of diagnostic test accuracy evaluations, Multivariate dose-response meta-analysis: the dosresmeta R package, Vancomycin-associated acute kidney injury in a large veteran population, Clinical outcomes of linezolid and vancomycin in patients with nosocomial pneumonia caused by methicillin-resistant, Effects of targeting higher vancomycin trough levels on clinical outcomes and costs in a matched patient cohort, More frequent premature antibiotic discontinuations and acute kidney injury in the outpatient setting with vancomycin compared to daptomycin, The association of vancomycin trough levels with outcomes among patients with methicillin-resistant, A prospective multicenter clinical observational study on vancomycin efficiency and safety with therapeutic drug monitoring, Optimization of time to initial vancomycin target trough improves clinical outcomes, Identification of risk factors for nephrotoxicity in patients receiving extended-duration, high-trough vancomycin therapy. 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