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      Evaluation of traditional initial vancomycin dosing versus utilizing an electronic AUC/MIC dosing program

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          Abstract

          Background:

          Area under the curve to minimum inhibitory concentration (AUC/MIC) has been recommended by the 2020 updated vancomycin guidelines for dosing vancomycin for both efficacy and safety. Previously, AUC/MIC has been cumbersome to calculate so surrogate trough concentrations of 15-20 mg/dL were utilized. However, trough-based dosing is not a sufficient surrogate as AUC/MIC targets of 400-600 can usually be reached without achieving troughs of 15-20 mg/dL. Targeting higher trough levels may also lead to adverse events including acute kidney injury (AKI) and nephrotoxicity.

          Objective:

          To compare the mean total first day vancomycin dose in traditional trough-based dosing versus dosing recommended by an AUC/MIC dosing program.

          Methods:

          Adult inpatients who received at least 24 hours of IV vancomycin treatment were included in this single-center, retrospective cohort study. The primary endpoint was difference in mean total first day vancomycin dose in milligrams (mg) received between patients’ traditional trough-based dosing and recommended dose via AUC/MIC electronic dosing calculator. Patients served as their own control by analyzing both actual dose received and dose recommended by the electronic AUC/MIC program. Rates of vancomycin induced adverse events, including acute kidney injury, elevated steady-state trough concentrations, and Red Man’s syndrome were also compared between patients who received doses consistent with the AUC/MIC dosing recommendation versus those who did not.

          Results:

          264 patients were included in this study. Initial 24-hour vancomycin exposure was significantly lower with the recommended AUC/MIC dose versus the dose received (2380.7; SD 966.6 mg vs 2649.6; SD 831.8 mg, [95% CI 114.7:423.1] p=0.0007).

          Conclusions:

          Utilizing an electronic AUC/MIC vancomycin dosing calculator would result in lower total first day vancomycin doses.

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          Most cited references18

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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

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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.

            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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              Are vancomycin trough concentrations adequate for optimal dosing?

              The current vancomycin therapeutic guidelines recommend the use of only trough concentrations to manage the dosing of adults with Staphylococcus aureus infections. Both vancomycin efficacy and toxicity are likely to be related to the area under the plasma concentration-time curve (AUC). We assembled richly sampled vancomycin pharmacokinetic data from three studies comprising 47 adults with various levels of renal function. With Pmetrics, the nonparametric population modeling package for R, we compared AUCs estimated from models derived from trough-only and peak-trough depleted versions of the full data set and characterized the relationship between the vancomycin trough concentration and AUC. The trough-only and peak-trough depleted data sets underestimated the true AUCs compared to the full model by a mean (95% confidence interval) of 23% (11 to 33%; P = 0.0001) and 14% (7 to 19%; P < 0.0001), respectively. In contrast, using the full model as a Bayesian prior with trough-only data allowed 97% (93 to 102%; P = 0.23) accurate AUC estimation. On the basis of 5,000 profiles simulated from the full model, among adults with normal renal function and a therapeutic AUC of ≥400 mg · h/liter for an organism for which the vancomycin MIC is 1 mg/liter, approximately 60% are expected to have a trough concentration below the suggested minimum target of 15 mg/liter for serious infections, which could result in needlessly increased doses and a risk of toxicity. Our data indicate that adjustment of vancomycin doses on the basis of trough concentrations without a Bayesian tool results in poor achievement of maximally safe and effective drug exposures in plasma and that many adults can have an adequate vancomycin AUC with a trough concentration of <15 mg/liter.
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                Author and article information

                Contributors
                Journal
                Pharm Pract (Granada)
                Pharm Pract (Granada)
                Pharmacy Practice
                Centro de Investigaciones y Publicaciones Farmaceuticas
                1885-642X
                1886-3655
                Jul-Sep 2020
                15 September 2020
                : 18
                : 3
                : 2024
                Affiliations
                PharmD. College of Pharmacy and Health Sciences, Campbell University . Buies Creek, NC (United States). kamcgrady1006@ 123456email.campbell.edu
                BS. College of Pharmacy and Health Sciences, Campbell University . Buies Creek, NC (United States). mlbenton0527@ 123456email.campbell.edu
                PharmD. Cape Fear Valley Health . Fayetteville, NC (United States). start@ 123456capefearvalley.com
                PharmD. College of Pharmacy and Health Sciences, Campbell University . Buies Creek, NC (United States). bowers@ 123456campbell.edu
                Author information
                https://orcid.org/0000-0001-6594-1301
                https://orcid.org/0000-0001-5553-5529
                https://orcid.org/0000-0002-6064-5762
                https://orcid.org/0000-0002-6889-0156
                Article
                pharmpract-18-2024
                10.18549/PharmPract.2020.3.2024
                7508472
                762265b7-d9fd-4241-9ffd-2fae3783617e
                Copyright: © Pharmacy Practice and the Authors

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY-NC-ND 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 09 June 2020
                : 06 September 2020
                Categories
                Original Research

                vancomycin,drug monitoring,area under curve,microbial sensitivity tests,acute kidney injury,software,inpatients,retrospective studies,united states

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