Drugs that follow a zero order model will at low doses appear to follow first order (linear) elimination up until the point that the elimination mechanism becomes saturated. By using this website, you agree to its use of cookies. A value of 0.7 L/kg is a convenient population estimate. The Sawchuk-Zaske method uses two post-dose concentrations (regardless of being at steady state) using the following approach:11. 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. Two drug levels (peak and trough) collected after a single dose (non-steady state), Two drug levels (peak and trough) collected at steady state (after at least three doses). If the clinician wants to adjust the patients daily vancomycin dose or change from a twice daily to a daily or every other day regimen, these programs are customizable to allow for this flexibility. Although vancomycin historically has been classified as a concentration-dependent antibiotic, in more recent years, it has been informally classified as "exposure" or "AUC-dependent". 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. Check out the new advanced version of this calculator that also has built-in levels. CLvanco is estimated using the most appropriate published pharmacokinetic model for a given patient. Notably, By integrating overall concentration over time, the AUC provides a more accurate estimate of the overall drug exposure. DoseMeRx Vancomycin Dosing Calculator (free version) Link to calculator is here.. 1. Estimating Creatinine Clearance (ml/min) -, Rybak MJ, Le J, Lodise TP,Levine DP, Bradley JS, Liu C, et al. Complete training and ensure all super users are present for the implementation date and at minimum for one-week post-implementation to answer questions. David McAuley, Pharm.D. Early and frequent monitoring of AUC exposure is recommended for dose adjustment, especially when empiric doses exceed 4,000 mg/day (A-II). Calculate the elimination rate constant (ke), Time from start of infusion to peak (T1, hours): 2. If the implementation of a Bayesian software program is your goal, consider reviewing this complete AUC conversion toolkit. 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. It cannot adapt to different conditions such as rapidly improving or declining renal function. While we strive to always be your go-to resource for a spanning array of calculation needs, please realize there are occasionally limitations to the tools we can provide. Even in patients with a baseline normal renal function, the risk of nephrotoxicity from vancomycin is too great to go without collection and monitoring of vancomycin levels. This is to ensure the highest degree of safety and accuracy. The Buelga model is a commonly selected in vancomycin Bayesian modeling and has been well studied in a variety of patient populations. Users can select a variety of other Vd options, including 0.7 L/kg (Bauer method). Vancomycin peak and trough concentrations are obtained under steady-state conditions. This vancomycin calculator uses pharmacokinetic population estimates, Bayesian modeling, and the Sawchuk-Zaske method to calculate a vancomycin dosing regimen for an adult patient. 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. See. This presents a challenge for the first order equations, as these equations assume that the drug follows one compartment pharmacokinetics. Unfortunately, there is only reliable AUC:MIC efficacy data for vancomycin against staph aureus. Sawchuk R and Zaske D. Pharmacokinetics of dosing regimens which utilize multiple intravenous infusions: gentamicin in burn patients. Vancomycin AUC FAQ . See source below for the complete guidelines. 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. Why did you pick Buelga 2005 as a general hospitalized Bayesian model? Initial dosing based on a target AUC is also available. In general, this error is produced in cases of data entry or laboratory error. When this saturation takes place, the rate of alcohol metabolized through this pathway no longer increases in relationship to increasing alcohol amounts.15,16, Increasing alcohol ingestion will also prolong the elimination half-life, as the elimination rate no longer increases proportionally with the drug concentration.15,17. Vancomycin single-level - dose infused early or late The GlobalRPh vancomycin single-level calculator uses the Vd recommended in Bauer's text: 0.7 L/kg. 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 this can be an effective method for drug monitoring of some medications, it alone cannot be used to determine the AUC. From here, the true peak (Cmax) can be extrapolated using the difference in time between the expected peak and the first drug level (Cpeak) using the following equation: In this case, t is the time between the observed peak (i.e., the drug level drawn from the patient) and the true peak, back-extrapolated. Vancomycin Per Pharmacy Protocol . The one compartment model is the most simplistic way of describing how a drug distributes and is eliminated from the body. 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. To calculate vancomycin dosage, please view the DoseMeRx calculator. Drug elimination pharmacokinetics can be divided into two main categories: zero order and first order. The latest article from SIDP illustrates the challenges of area under the curve (AUC) implementation and offers . "Based on current national vancomycin susceptibility surveillance data, under most circumstances of empiric dosing, the vancomycin MIC should be assumed to be 1 mg/L. Bayesian estimation is based on Bayes Theorem. These drug levels can either be obtained after the first dose is given (non-steady state) or once steady state is achieved (after the third dose is administered). Initial dosing based on a target AUC is also available. For these reasons, this method of determining AUC may be used for both adults and children. Thus, the single trough level became the gold standard for vancomycin monitoring. 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. File: UCSF Vancomycin AUC calculator.xls. Once patient-specific values of Kel and Vd have been determined, traditional one-compartment pharmacokinetic equations are used to identify a dose and its associated peak, trough, and AUC/MIC values. Steady-state requires 4-5 elimination half-lives. 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. Since drug level monitoring alone was found to be less effective than directly monitoring the AUC, more complex calculations are needed. 1 Vancomycin has found significant use in clinical practice due to its activity against these organisms. \\CL_{vanco} = (0.698*CrCl+3.66)*0.06 Trough drawn early? by levels. 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. First, since vancomycin is primarily cleared in the kidneys,1 AKI makes dosing the patients vancomycin much more difficult and imprecise. Vancomycin regimens can be calculated both empirically (without any prior doses) or using one or two vancomycin levels. By targeting a trough level of at least 15 mcg/mL and ideally no greater than 20 mcg/mL, the clinician could assume that the AUC/MIC would be 400 assuming an S. aureus vancomycin MIC of 1 mcg/mL. 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 . Vancomycin dosing must be tailored to the patient and closely monitored given its narrow therapeutic index2 and risky adverse effects. Owner: DoseMe Pty Ltd. Last updated: Not found, however this is a new calculator so assume October 2018. 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. In these articles, trough-only monitoring was not well correlated with improved clinical outcomes and maintaining a trough level in the range of 15-20 mcg/mL consistently failed in predicting clinical cure and AKI risk. Vancomycin AUC/MIC ratio and 30-day mortality in patients with Staphylococcus aureus bacteremia. One approach used by some facilities is the creation of spreadsheet or electronic health record integrated calculators. Vancomycin Dosing Calculator Try the free DoseMeRx vancomycin dosing calculator. Background: Vancomycin area under the curve/minimum inhibitory concentration (AUC/MIC) has been proposed as a therapeutic drug monitoring (TDM) target to dose vancomycin. 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). 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. 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). 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. "In patients with suspected or definitive serious MRSA infections, an individualized target of the AUC/MIC BMD ratio of 400 to 600 (assuming a vancomycin MIC BMD of 1 mg/L) should be advocated to achieve clinical efficacy while improving patient safety (A-II). An initial loading dose of 25 mg/kg is recommended followed by 7.5 to 10 mg/kg after each hemodialysis session. The information provided by the MAD-ID Vancomycin Task Force ("we," "us" or "our") on this website (the "Site") is for general informational purposes only. Sabourenkov P and McLeay R. Predictive ability and bias of vancomycin population PK models in an obese adult population. This method relies on having two post-dose drug levels from the same dosing interval ideally collected at steady state. 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. $$, $$ single-level dose infused early or late, HONcode standard for trust- worthy health, pediatric liver transplantation: a new biological abdominal wall. A patient-specific Vd can be calculated using Cmax and Cmin from the previous step. For users who would like to use a specific volume of distribution value (L/kg), this option can be selected. Jeffres M. The whole price of vancomycin: toxicities, troughs, and time. Literature demonstrates that these population estimates vary widely in certain patient populations, such as morbidly obese or critically ill patients. First, it can only be used to inform the clinician of the drug concentration at a certain time point. AUC total Target AUC24 is 400-600 Acceptable vancomycin peaks should be <50 tpeakmeasured AUCtotal Dose Used T used tinf Used tinf used Revised Dose Calcs Initial Dose Calcs Actual Trough level Interval Used Cpeak actual Ctrough actual Vancomycin AUC24 Note: assumes vancomycin volume of distribution is constant; caution with obesity, fluid . This recommendation is of most importance when considering patients that are critically ill and need more intensive drug monitoring for a serious infection. The peak is reported as 22 g/mL, trough 8 g/mL. 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. The vancomycin mean 24-h plasma free drug AUC/MIC values associated with 1-log kill were 282 and 113 for the thigh and lung models, respectively (P = 0.19). In 2009 when this consensus guidance was released, the only AUC calculation method that was available for the hospital clinician required two serum concentrations to perform pharmacokinetic calculations by hand. Doses are entered (not selected), so they are not constrained by the size of doses typically used in adults. 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. Doses of 15 to 20 mg/kg (based on actual body weight) administered every 8 to 12 hours as an intermittent infusion are recommended for most patients with normal renal function when assuming a MICBMD of 1 mg/L (A-II). A full description of how to perform these calculations can be found here. This vancomycin calculator uses pharmacokinetic population estimates, Bayesian modeling, and the Sawchuk-Zaske method to calculate a vancomycin dosing regimen for an adult patient. DoseMe-Rx more than other published studies. UCSF Vancomycin AUC calculator; UCSF Vancomycin AUC calculator. 2013;57(4):1654-1663. Two postdistributional concentrations obtained at steady state are used to determine AUC. Alcohol is a commonly used example of zero order (nonlinear) kinetics. 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. -Estimation Tool based on entered Kel, Vancomycin -Timing of next dose based on estimated Ke At DoseMe, we support all dosing approaches of vancomycin and have helped several hospitals with the transition to AUC-based decision making - calculating AUC side-by-side with trough targets - and even helping by analyzing clinical datasets to aid hospitals and health systems in supporting a move. 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