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. Thus, the single trough level became the gold standard for vancomycin monitoring. It should be noted that currently available nomograms were not developed to achieve these targeted endpoints. Doses are entered (not selected), so they are not constrained by the size of doses typically used in adults. For users who would like to use a specific volume of distribution value (L/kg), this option can be selected. Calculating the AUC requires a bit of work. UCSF Vancomycin AUC calculator; UCSF Vancomycin AUC calculator. Alcohol is a commonly used example of zero order (nonlinear) kinetics. 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. If a patient has only received one single dose (thus not at steady state), Cmin is set to 0 (zero). more than other published studies. Clearance is then determined using the following steps: Two drug levels available (peak and trough): This is the most accurate method of calculating a patient-specific CLvanco and Vd; however, it requires two drug levels to be drawn. by levels. Blood samples should be collected to adjust maintenance dosing to a goal AUC/MIC between 400 to 600 mg*h/L. Preparing patients to discharge on vancomycin for outpatient parenteral antimicrobial therapy will present challenges if they are receiving their vancomycin through a home infusion company or are discharged to another facility that remains on a trough-only monitoring protocol. ClinCalc: 2022 - ClinCalc LLC. To most effectively and consistently do this, clinicians must have a thorough understanding of the available therapeutic drug monitoring guidelines, pharmacokinetics, and the tools and calculation methods at their disposal. This vancomycin calculator uses pharmacokinetic population estimates, Bayesian modeling, and the Sawchuk-Zaske method to calculate a vancomycin dosing regimen for an adult patient. First, since vancomycin is primarily cleared in the kidneys,1 AKI makes dosing the patients vancomycin much more difficult and imprecise. Sabourenkov P and McLeay R. Predictive ability and bias of vancomycin population PK models in an obese adult population. The following methods can be used to estimate vancomycin volume of distribution (Vd). CLvanco is determined using whichever "Clearance method" is selected (see Methods for Determining Vancomycin Clearance). and review of 1the American Society of Health-System Pharmacists, It cannot adapt to different conditions such as rapidly improving or declining renal function. Spend more time on patients, less on calculations. value, Vancomycin Predicted Trough-Level drawn early, Dosing by levels pharmacokinetics (quick), Pharmacokinetics -Multiple Ke (Advanced version), Pharmacokinetic dosing -aminoglycosides/Vanco Original program, Vancomycin SINGLE Level-(dosing by levels) Original calc, Vancomycin single-level dose infused early or late, Vancomycin single level Advanced version, HONcode standard for trust- worthy health, pediatric liver transplantation: a new biological abdominal wall. No sign-in needed. The latest article from SIDP illustrates the challenges of area under the curve (AUC) implementation and offers . Enter New Dose Enter your new dose, dosing interval, and duration of infusion and click "Calculate." Adjust or Export 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). This method relies on having two post-dose drug levels from the same dosing interval ideally collected at steady state. \\ (rewritten\;to\;solve\;for\;k) 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. What this means is that its killing action is really dependent upon both the concentrations reached in the body as well as the time that those . 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. First, it can only be used to inform the clinician of the drug concentration at a certain time point. Vancomycin AUC Calculation Brandon Reynolds, Pharm.D., BCPS Vancomycin is a glycopeptide antibiotic with activity against methicillin-resistant Staphylococcus aureus (MRSA)as well as other clinically important gram-positive organisms. To make this practice change, calculator support will be . Provide education to staff pharmacists, nurses, and physicians regarding the need to add vancomycin peaks for all patients being monitored on vancomycin therapy, Create a dosing calculator that can either be used within the electronic medical record or on a shared spreadsheet file, Update any dosing protocols and monitoring sheets to reflect the updated guidance which reviews how the AUC can be hand calculated should a situation arise where the above calculator is not available, After implementation, continuously evaluate the workflow impact and patient outcomes of this method of AUC dosing. 1. \\ k = ln(Cp^0/Cp)/t and review of 1the American Society of Health-System Pharmacists, What to Use: Chemical or Natural Sunscreens? CL_{vanco} = (0.695*CrCl/TotalBW + 0.05)*TotalBW*0.06 In selected patients, a loading dose (25-30 mg/kg of total body weight; maximum 3000 mg) may be considered in order to achieve rapid attainment of serum concentrations.12 Patients who should be considered for a loading dose include those who are critically-ill, those receiving renal replacement therapy, or those receiving a continuous infusion of vancomycin. This step should not be skipped as it lays out the necessary groundwork to ensure that the project will be successful. Consider performing post-implementation auditing to ensure the program is being used effectively. The provider can then input a new combination of dose, duration of infusion, and dosing interval, and the calculator predicts the AUC 24, peak, and trough concentration that should result. Similarly, a true trough (Cmin) can be calculated using the time elapsed between the second drug concentration (Cp) and the when the next dose is due to begin infusing. Given that, this calculator selects one of four possible pharmacokinetic models to estimate a patient's pharmacokinetic parameters: There are many models available for pharmacokinetic and Bayesian analyses.5,6 These models were selected based on being generalizable, one-compartment models with reasonable predictive performance in confirmatory publications. Blood samples may be collected before dialysis (pre-dialysis) or 1-2 hours after dialysis (post-dialysis) and should be used to adjust maintenance dosing to a goal AUC/MIC between 400 to 600 mg*h/L. Alcohol dehydrogenase, one of the major enzymes involved in alcohol metabolism, has a low Km, which is a measure of the affinity of the substrate for an enzyme. Commonly, the trapezoidal rule is used to calculate the AUC by hand. These calculations can be done with a calculator, paper and pencil, using an Excel spreadsheet, or via an online calculator such as the, Answers to some common questions about therapeutic vancomycin monitoring can be found at. The most optimal method of monitoring vancomycin therapy is to obtain two drug levels (such as a peak and trough concentration) during the same dosing interval. 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 . Rybak, M. The pharmacokinetic and pharmacodynamic properties of vancomycin. This site complies with the HONcode standard for trust- worthy health information: verify here. [. Press 'Calculate' to view calculation results. 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. This included recommendations on empiric dosing according to the patients body weight, adjusting the dose of vancomycin based on the patients CrCl, and intensifying the dosing strategy if the patient had a confirmed, serious infection caused by MRSA such as endocarditis. This recommendation is of most importance when considering patients that are critically ill and need more intensive drug monitoring for a serious infection. All information on the Site is provided in good faith, however we make no formal endorsement (s) of any kind regarding use of any proprietary materials found within this content. With readily accessible and easy-to-use Bayesian estimation software, healthcare systems and clinicians are empowered to make this change from trough to AUC for the betterment of their patients. While this can be an effective method for drug monitoring of some medications, it alone cannot be used to determine the AUC. While there were some small studies conducted in humans, most were in animals or in a laboratory setting (in vitro).3. Although the model was developed in patients with hematological malignancies, it has been validated in a more general cohort of hospitalized patients. Rybak MJ, Le J, Lodise TP,Levine DP, Bradley JS, Liu C, et al. Although values are highly variable, a Vd of 0.52 L/kg is a reasonable population estimate supported by the literature. Diseases Society and the Society of Infectious Diseases Pharmacists. All Rights Reserved. download a printer-friendly version of this information here, Area under the serum concentration vs. time curve for 0-24 hours (AUC, Note: traditional pediatric dosing of 45-60 mg/kg/day frequently does not achieve target AUC in term infants and older children with normal renal function. This equation also allows the elimination rate constant of the drug to be calculated, starting with the following equation: Where k = the elimination rate constant, Cpeak is the observed peak level collected, Ctrough is the observed trough level, and t is the difference in time in hours between the Cpeak and the Ctrough levels. Identify a publication describing mean and variance of vancomycin clearance and volume of distribution. If a single drug level is available, Bayesian modeling can be used to optimize the population estimates of CLvanco and Vd. With all of the necessary parameters and an understanding of how to calculate the AUC, any adjustments to the dose of vancomycin or modifications in dosing frequency can all be calculated by the user. 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. De-escalation Guide (Vancomycin) Patient Case Tutorial . Using a population estimate of Vd, extrapolate a peak value: Using the extrapolated peak and trough values, calculate Kel and CL. Two postdistributional concentrations obtained at steady state are used to determine AUC. A value of 0.7 L/kg is a convenient population estimate. Do Not Copy, Distribute or otherwise Disseminate without express permission. Hand calculations were cumbersome and the several steps involved increased the risks for errors. $$, $$ 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. Literature demonstrates that these population estimates vary widely in certain patient populations, such as morbidly obese or critically ill patients. Drug elimination pharmacokinetics can be divided into two main categories: zero order and first order. An initial loading dose of 15 to 25 mg/kg is recommended followed by a maintenance dose based on the CRRT modality (see below). There is insufficient evidence to provide recommendations on whether trough-only or AUC-guided vancomycin monitoring should be used among patients with noninvasive MRSA or other infections." If two drug levels are collected over the same dosing interval, the clinician can then solve for the elimination rate constant (k) and use this equation to provide an estimation of vancomycin concentration. Therapeutic monitoring of vancomycin: A revised consensus guideline While there are several limitations to consider when using first order pharmacokinetic equations, there are some potential benefits. Holmes N, Turnidge J, Munckhof W, et al. 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. While this was a necessary step towards more appropriate dosing and monitoring of vancomycin, patients were still at risk for side effects from the drug.4-7. Sawchuk R and Zaske D. Pharmacokinetics of dosing regimens which utilize multiple intravenous infusions: gentamicin in burn patients. This AUC was compared to the AUC from two (AUC-2) and one (AUC-1) sample(s) by excluding the second and third (AUC-2) or the first, second and third (AUC-1) sample for calculation. Typically, the first level will be a post infusion peak and the second level is a trough level. In patients with normal renal function, these doses may not achieve the therapeutic AUC/MIC target when the MIC is 2 mg/L." Steady-state requires 4-5 elimination half-lives. In the busy hospital environment, collection of a peak and trough level is often a challenging obstacle and involves many moving parts. If drug levels were collected, there was not a well-established method of determining if the patient was adequately treated or at risk for acute kidney injury (AKI). Note that this recommendation is made on the basis of expert opinion and is not supported by clinical trial data. Antibiotic Allergies Antibiotic Allergy Clinical Decision Support Tool (intranet) Antibiotic Allergy Tool - Rationale Document (intranet) When the MICBMD is >1 mg/L, the probability of achieving an AUC/MIC target of 400 is low with conventional dosing; higher doses may risk unnecessary toxicity, and the decision to change therapy should be based on clinical judgment. , Bayesian modeling can be an effective method for drug monitoring of some medications, it can only be to... 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