Do Not Copy, Distribute or otherwise Disseminate without express permission. AUC24 is calculated using either Bayesian modeling, which falls outside the scope of this document, or a more transparent "trapezoidal" model, which calculates AUC through the measurement of two trapezoids which fill most of the area under the curve. First, since vancomycin is primarily cleared in the kidneys,1 AKI makes dosing the patients vancomycin much more difficult and imprecise. Bayesian modeling is not conducted when no drug levels are available (a level is necessary for the model) nor when two drug levels are available (the Sawchuk-Zaske method is more reliable). Users can select a variety of other Vd options, including 0.7 L/kg (Bauer method). This method relies on having two post-dose drug levels from the same dosing interval ideally collected at steady state. DoseMe is a registered trademark of DoseMe Pty Ltd. DoseMeRx and DoseMe are service marks of DoseMe LLC. Spend more time on patients, less on calculations. 2018); however, these models utilize a two-comparment approach. In general, this error is produced in cases of data entry or laboratory error. Once CLvanco, Vd, and Kel are determined, one-compartment pharmacokinetic equations can be used to determine the peak, trough, and AUC/MIC for a given regimen: When CLvanco or Vd are unknown, population estimates are used based on published literature. Seeing that this was not reasonable for clinical practice at the time, the authors decided to recommend trough-only monitoring as a convenient surrogate marker for this ratio. Calculated EDD = AUC x CL nonobese EDD final (w/max) Display OBESITY Weight-based obesity dosing Clvan obese (Crass et al, 2018) 15 mg/kg 25 mg/kg/d Clvan max (cap at CrCl 150ml/min or 9L/hr) 15 mg/kg max Clvan obese display (w/age validation) TDD using Clvan obese 20 mg/kg 30 mg/kg TDD final using Clvan obese (cap at 4500) max Age validation Ex 2. if trough was 12 with AUC 400, target trough range 1217 mg/L.-Option to calculate: Calculate lower (x) and upper (y) limits of target range using linear proportionality Using Ex 1 above: o Lower limit: 12/500=x/400 = 9.6 10 [. What is known and objective: The revised vancomycin monitoring guidelines recommend targeting an area under the curve (AUC) of 400-600 mg*hr/L for serious methicillin-resistant Staphylococcus aureus (MRSA) infections. There are three ways to calculate vancomycin clearance from levels (without the use of a population Vd model): 1) Two levels after the first dose, 2) a steady state peak and trough, or 3) three non-steady-state levels. Trough drawn early? 1. Other models do exist that may have less bias and more precision (such as Goti et al. Conduct an extensive literature review of AUC vancomycin dosing, specifically literature sources that utilize a Bayesian program if possible. Note that this recommendation is made on the basis of expert opinion and is not supported by clinical trial data. AUC is the preferred method of vancomycin monitoring Goal AUC is 400-600 regardless of MIC and should not be adjusted for MICs less than or equal to 1 . These data are entered into the calculator, spreadsheet, or equations: Time from start of infusion to trough (T2, hours): 11.5, Subsequent dose adjustments can be determined using the, 11771 Lee Hwy., PO Box 276, Sperryville, VA 22740 USA. Because the patient is at steady state, the trough concentration measured 30 minutes before the fourth dose will be equivalent to a trough measured 30 minutes before the fifth dose (refer to above graphic). if calculated AUC was 900 with 3g/day, a dose of 1.5g/d approximately correlates to an AUC of 450). Calculating the AUC requires a bit of work. Using the first-order elimination equation (\(Cp = Cp^0*e^{-kt}\)), a true peak (Cmax) can be calculated using the time elapsed between the end of the vancomycin infusion and the first drug concentration (Cp0). Vancomycin Calculator. If a patient has only received one single dose (thus not at steady state), Cmin is set to 0 (zero). David McAuley, Pharm.D. This site complies with the HONcode standard for trust- worthy health information: verify here. One potential cause for this finding was with the inability of the trough to function as a surrogate for the AUC. It should be noted, however, that there are limitations to using the first order equations in the calculation of the area under the curve. Using this information and the predictive power of Bayesian estimation, the program can use this information to provide a new dosing regimen to arrive within the goal AUC. While all methods will result in the same outputs, advantages of using an online calculator include easy access from any device, the ability to quickly copy or export results and append them to a patient record, and the ability to cite a specific source and methodology for A patient-specific Vd can be calculated using Cmax and Cmin from the previous step. An initial loading dose of 20 to 25 mg/kg is recommended followed by 15 mg/kg after the end of each hybrid hemodialysis session. All rights reserved. In the clinical setting, patients often present with multiple comorbidities, varying ranges of body weight and body mass index (BMI), and rapidly changing creatinine clearance (CrCl). \\ (rewritten\;to\;solve\;for\;k) As with many drugs, vancomycin has been modelled as following two- or even three-compartment pharmacokinetics.1,5,13. From here, the true trough (Cmin) can be calculated using the Cmax from the following formula: Where Tau is the dosing interval and tinf is the infusion time in hours. The only solution was to forego surrogate markers and calculate the AUC directly. If your health system has an infectious disease physician team and/or antimicrobial stewardship program, rally for their support. \\CL_{vanco} = (0.698*CrCl+3.66)*0.06 In the critical care patient population, the availability of albumin to bind free drug decreases,17 volume of distribution increases as a result of excess fluid administration and third spacing of fluid, and renal function often decreases or undergoes rapid changes. Blood samples may be collected before hybrid dialysis (pre-dialysis) or 1-2 hours after hybrid dialysis (post-dialysis) and should be used to adjust maintenance dosing to a goal AUC/MIC between 400 to 600 mg*h/L. Diseases Society and the Society of Infectious Diseases Pharmacists. Calculator >> Patient-Specific Data: Patient: Location: Age: Sex: One or more vancomycin concentrations are drawn from a patient. In the 2020 update to the consensus guidelines for the therapeutic monitoring of vancomycin, trough-only monitoring was officially no longer recommended with direct monitoring of the AUC used in its place.14. For these reasons, this method of determining AUC may be used for both adults and children. Vancomycin peak and trough concentrations are obtained under steady-state conditions. A key assumption of the dual trapezoid method of calculating vancomycin AUC is that the peak and trough concentrations are obtained under steady-state conditions. It should be noted that while the collection of a single drug level at any time point is likely within reason for a Bayesian software program to provide a valid dosing recommendation, the 2020 consensus guidelines do recommend the collection of two drug levels, specifically in patients that may be at risk of altered pharmacokinetics. 1,3,4 for years, pharmacists in inpatient and outpatient infusion settings have been involved heavily in the dosing and monitoring of vancomycin, because of the complex interplay between Vancomycin Online AUC Calculator User Guide . Vancomycin Per Pharmacy Protocol . For example, blood flow rate, filter type, hemodialysis frequency or downtime, effluent rate, and residual renal function are among several factors that influence a patient's vancomycin dosing needs. Use of AUC. It is time-consuming to estimate AUCs using traditional methods. by levels. Prybylski J. Vancomycin trough concentration as a predictor of clinical outcomes in patients with, Borowy, C and Ashurst J. Physiology, zero and first order kinetics. DoseMeRx Vancomycin Dosing Calculator (free version) Link to calculator is here.. Therapeutic monitoring of vancomycin: A revised consensus guideline While this can be an effective method for drug monitoring of some medications, it alone cannot be used to determine the AUC. This site complies with the HONcode standard for trust- worthy health information: verify here. For users who would like to use a specific volume of distribution value (L/kg), this option can be selected. One drug level available (trough): Vd is assumed using either a population estimate or a user-specified Vd. Early and frequent monitoring of AUC exposure is recommended for dose adjustment, especially when empiric doses exceed 4,000 mg/day (A-II). Although values are highly variable, a Vd of 0.52 L/kg is a reasonable population estimate supported by the literature. Vancomycin regimens can be calculated both empirically (without any prior doses) or using one or two vancomycin levels. The following equations are used as part of these models: CLvanco is estimated using a linear relationship to creatinine clearance while normalizing to total body weight: CLvanco is estimated using a linear relationship to creatinine clearance: Note that this method comes from the same manuscript that published the linear relationship between Kel and CrCl (Kel=0.00083*CrCl+0.0044), sometimes called the Creighton equation. Diseases Society and the Society of Infectious Diseases Pharmacists. While a trough goal between 15 and 20 mcg/mL usually represented an AUC of at least 400, it also had the tendency to overshoot the therapeutic range of the drug, predisposing patients to the aforementioned complications of kidney damage. Sawchuk R and Zaske D. Pharmacokinetics of dosing regimens which utilize multiple intravenous infusions: gentamicin in burn patients. For health systems, this meant that anyone monitoring and adjusting vancomycin doses needed to move away from the traditional trough goals and towards a method of calculating the AUC. David McAuley, Pharm.D. This theorem is a mathematical formula that can be used to determine the probability of an event occurring based on the condition(s) placed on the event and the probability model (Bayesian prior) used as a guide. As staph aureus is the most invasive of the organisms vancomycin is used to treat, it is hoped that other pathogens will be adequately covered by a vancomycin AUC in the 400 to 600 range. CLvanco is determined using whichever "Clearance method" is selected (see Methods for Determining Vancomycin Clearance). A core goal of this calculator is to provide transparency in how a vancomycin dose is calculated -- clinicians (and pharmacokinetic textbooks) utilize one-comparment pharmacokinetics; therefore, only one-comparment Bayesian models are considered for this calculator. For example, if a patient received a loading dose of vancomycin or doses that were given early or late, the program can provide a recommended dose adjustment based on the amount and timing of drug administration. $$, $$ Typically, the first level will be a post infusion peak and the second level is a trough level. Vancomycin dosages of 15-20 mg/kg (based on ABW) given every 8-12 hours are required for most patients with normal renal function to achieve the suggested serum concentrations when the MIC is 1 mg/L. Check out the new advanced version of this calculator that also has built-in levels. When selecting an initial dose consider targeting an AUC of 500-600 to ensure therapeutic drug levels at the start of therapy. The Sawchuk-Zaske method uses two post-dose concentrations (regardless of being at steady state) using the following approach:11. $$, $$ This step should not be skipped as it lays out the necessary groundwork to ensure that the project will be successful. Estimated AUC:MIC (over 400 desired) As determined by ( (daily vancomycin dose)/ (ClCr*0.75*0.06))/ (MIC) Evidence Latest Episodes Vd estimates are determined based on creatinine clearance: Vd estimates are determined using an equation incorporating age (in years) and total body weight (in kg): Among non-critically ill, morbidly obese patients (defined as BMI > 40 kg/m2 and body weight 120 kg), Vd (L/kg) is smaller per kilogram of total body weight. the Infectious Diseases Society of America, the Pediatric Infectious Therapeutic Vancomycin Monitoring Using AUC How it Works Enter Values Enter starting values and click "Calculate" to determine current AUC24. Am J Health Syst Pharm. Toolkit Features: Template guideline for vancomycin dosing with highlighted areas to customize to your local facility \\CL_{vanco} = Vd*Kel \\ Cp = Cp^0*e^{-kt} Copyright 2021 GlobalRPH - Web Development by. The distinguishing factor between zero order and first order pharmacokinetics is the ability of the elimination system to become saturated by the drug.15, When administered intravenously, vancomycin is eliminated renally with >80% of the administered drug recoverable unchanged in the urine.1, While there are other means of vancomycin elimination, renal function plays the most central role in determining how quickly a patient can remove vancomycin from the central compartment. This toolkit provides helpful advice and strategies to completing the following implementation steps and more. All Rights Reserved. The measured peak and trough concentrations are back-extrapolated and forward-extrapolated to the true peak and true trough, respectively, to capture as much of the AUC for one dosage interval as possible. When the 2009 vancomycin consensus guidelines for the therapeutic monitoring of vancomycin were released, available literature that could be used to determine the therapeutic monitoring goal for vancomycin was limited. Once the most likely values of Kel and Vd have been estimated, one-compartment pharmacokinetic equations are used to identify a dose and its associated peak, trough, and AUC/MIC values. Jeffres M. The whole price of vancomycin: toxicities, troughs, and time. It is important to note the limitations in automated susceptibility testing methods, including the lack of precision and variability in MIC results depending on method used (B-II)." Literature demonstrates that these population estimates vary widely in certain patient populations, such as morbidly obese or critically ill patients. If the implementation of a Bayesian software program is your goal, consider reviewing this complete AUC conversion toolkit. Empiric, initial vancomycin dosing will be calculated using population pharmacokinetic parameters. First, it can only be used to inform the clinician of the drug concentration at a certain time point. The 2020 consensus guideline updates recommend Bayesian estimation as the preferred approach to monitoring the AUC. For example, if a patient with very poor renal function (CrCl 20 mL/min) is given a very large dose (15 mg/kg IV Q8hr), the model would anticipate a very high trough level. Accessed: May 2019. [BMD]- MIC determined by broth microdilution. Literature demonstrates highly variable values ranging from less than 0.5 L/kg (in morbidly obese patients) to greater than 1 L/kg (in non-obese critically ill patients). There are several models available that can be used as the Bayesian prior.21-25 These include models for the standard, critically ill, or obese, the adult patient on hemodialysis, and pediatric/adolescent and preterm/neonate models. Date Uploaded: Thursday, February 6, 2020 - 9:30am. 5. Complete training and ensure all super users are present for the implementation date and at minimum for one-week post-implementation to answer questions. In addition to the research that was released between 2009 and 2020, there was also a very significant development in the realm of AUC estimation: the creation of commercially available Bayesian estimation software programs. Also include current dose and interval in the levels section if dosing See source below for the complete guidelines. van Hal S, Paterson D, and Lodise T. Systematic review and meta-analysis of vancomycin-induced nephrotoxicity associated with dosing schedules that maintain troughs between 15 and 20 milligrams per liter. Blood samples should be collected to adjust maintenance dosing to a goal AUC/MIC between 400 to 600 mg*h/L. Bayesian modeling is a mathematically complex process that involves the following steps: When multiple vancomycin drug concentrations are available, traditional pharmacokinetic equations can be implemented to calculate patient-specific pharmacokinetic parameters. This calculator is not designed for patients receiving any form of renal replacement therapy (such as intermittent hemodialysis, SLED, or CRRT). It is for these reasons that vancomycin pharmacokinetic studies in critically ill patients in the ICU often use a two-compartment model.19. The Buelga model is a commonly selected in vancomycin Bayesian modeling and has been well studied in a variety of patient populations. Duration of Vancomycin infusion (Tinf, in hours), Measured Vancomycin peak concentration (g/mL), Time from start of Vancomycin infusion to measurement of peak concentration (T1, in hours), Measured Vancomycin trough concentration (g/mL), Time from start of Vancomycin infusion to measurement of trough concentration (T2, in hours). and review of 1the American Society of Health-System Pharmacists, Description: This is a 3-step calculator (patient data, previous doses, concentrations).It does not allow for calculations outside of weight 40-200kg, height 151-210 cm, age 18-100 years, SCr 0.1-3 mg/dL .
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