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Systematic Review and Meta-Analysis of Vancomycin-Induced Nephrotoxicity Associated with Dosing Schedules That Maintain Troughs between 15 and 20 Milligrams per Liter

TLDR
Overall, higher troughs (≥15 mg/liter) were associated with increased odds of nephrotoxicity, and the collective literature indicates that an exposure-nephrotoxicity relationship for vancomycin exists.
Abstract
In an effort to maximize outcomes, recent expert guidelines recommend more-intensive vancomycin dosing schedules to maintain vancomycin troughs between 15 and 20 mg/liter. The widespread use of these more-intensive regimens has been associated with an increase in vancomycin-induced nephrotoxicity reports. The purpose of this systematic literature review is to determine the nephrotoxicity potential of maintaining higher troughs in clinical practice. All studies pertaining to vancomycin-induced nephrotoxicity between 1996 and April 2012 were identified from PubMed, Embase, Cochrane Controlled Trial Registry, and Medline databases and analyzed according to Cochrane guidelines. Of the initial 240 studies identified, 38 were reviewed, and 15 studies met the inclusion criteria. Overall, higher troughs (≥15 mg/liter) were associated with increased odds of nephrotoxicity (odds ratio [OR], 2.67; 95% confidence interval [CI], 1.95 to 3.65) relative to lower troughs of <15 mg/liter. The relationship between a trough of ≥15 mg/liter and nephrotoxicity persisted when the analysis was restricted to studies that examined only initial trough concentrations (OR, 3.12; 95% CI, 1.81 to 5.37). The relationship between troughs of ≥15 mg/liter and nephrotoxicity persisted after adjustment for covariates known to independently increase the risk of a nephrotoxicity event. An incremental increase in nephrotoxicity was also observed with longer durations of vancomycin administration. Vancomycin-induced nephrotoxicity was reversible in the majority of cases, with short-term dialysis required only in 3% of nephrotoxic episodes. The collective literature indicates that an exposure-nephrotoxicity relationship for vancomycin exists. The probability of a nephrotoxic event increased as a function of the trough concentration and duration of therapy.

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Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists

TL;DR: The primary recommendations consisted of eliminating routine monitoring of serum peak concentrations, emphasizing a ratio of area under the curve over 24 hours to minimum inhibitory concentration (AUC/ MIC) of ≥400 as the primary PK/ PD predictor of vancomycin activity, and promoting serum trough concentrations of 15 to 20 mg/L as a surrogate marker for the optimal vancomYcin AUC/MIC if the MIC was ≤1mg/L in patients with normal renal function.
Journal ArticleDOI

The Surgical Infection Society Revised Guidelines on the Management of Intra-Abdominal Infection.

TL;DR: This guideline summarizes the current recommendations developed by the SIS task force on the treatment of patients who have IAI regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy.
Journal ArticleDOI

Prospective Trial on the Use of Trough Concentration versus Area under the Curve To Determine Therapeutic Vancomycin Dosing.

TL;DR: Compared to trough concentration targets, AUC-guided, Bayesian estimation-assisted vancomycin dosing was associated with decreased nephrotoxicity, reduced per-patient blood sampling, and shorter length of therapy, without compromising efficacy.
Journal ArticleDOI

The Nephrotoxicity of Vancomycin.

TL;DR: This work critically examines available data in adult patients pertinent to this question, and reviews the pharmacokinetics/pharmacodynamics of vancomycin metabolism, effectiveness and safety data, as well as investigating the potential synergistic nephrotoxicity of van comycin and piperacillin‐tazobactam.
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TL;DR: A 2-day consensus conference on acute renal failure (ARF) in critically ill patients was organized by ADQI as discussed by the authors, where the authors sought to review the available evidence, make recommendations and delineate key questions for future studies.
Journal ArticleDOI

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TL;DR: The Acute Kidney Injury Network (AKI Network) as discussed by the authors is a multidisciplinary collaborative network focused on AKI, which was established to improve care for patients with or at risk for AKI.
Journal ArticleDOI

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