Frequently asked questions

Why Vancomyzer is built the way it is.

How the model uses kidney function and body weight, and what has and has not been validated. Each answer cites its sources.

Questions12 answers. Open any question; the references are listed under each answer.

Is Vancomyzer free?

Yes. Access to Vancomyzer is currently free.

Where does Vancomyzer’s pharmacokinetic data come from?

Vancomyzer uses one population pharmacokinetic model for every adult: the Colin 2019 two-compartment population PK model. Its inputs are age, total body weight and serum creatinine.

Source data: Pooled population analysis of data from 14 studies (2,554 individuals), from neonates to elderly adults.

Scope in Vancomyzer: Adults (18 years and older) receiving intermittent IV vancomycin who are not on renal replacement therapy. Used for every body size, including BMI 40 kg/m2 and above.

Equations, parameter values and Vancomyzer’s own settings (such as the Bayesian prior widths) are published on the Equations & derivations page.

Colin PJ, et al. Vancomycin pharmacokinetics throughout life: results from a pooled population analysis and evaluation of current dosing recommendations. Clin Pharmacokinet. 2019;58(6):767-780.

Why doesn’t Vancomyzer use Cockcroft-Gault to estimate vancomycin clearance?

Because Colin 2019 was built with serum creatinine itself as the renal covariate. SCr enters clearance directly:

FSCR = exp(−0.649 × (SCr − SCRstd)), SCr in mg/dL

SCRstd is an age-standardized reference creatinine. Substituting a Cockcroft-Gault CrCl would mean running a different model from the one that was published and evaluated.

This is a property of the model, not evidence that one renal estimate is better for every patient. Cockcroft-Gault remains widely used for drug dosing, and all creatinine-based estimates share the same weakness when muscle mass is low (see “What about muscle mass?”).

What are the limitations of Cockcroft-Gault for vancomycin dosing?

Cockcroft-Gault was published in 1976 to estimate creatinine clearance in adult men (derivation data from 249 patients). It was not developed to predict vancomycin pharmacokinetics.

Like other creatinine-based estimates, it can mislead when muscle mass is low (older, sarcopenic or bedbound patients), when renal function is changing, and in critical illness. In obesity, the result depends heavily on which body weight is entered. It was also derived before creatinine assays were standardized (see the next question).

For assessing chronic kidney disease, KDIGO and the National Kidney Foundation favor eGFR equations such as CKD-EPI. That guidance is about CKD assessment: Cockcroft-Gault remains widely used for drug dosing.

How serum creatinine is measured matters — and it has changed

Clinical laboratories measure creatinine with two main methods:

Jaffe (alkaline picrate) method, first described in 1886: a colorimetric reaction that is less specific. Glucose, bilirubin, acetoacetate and some cephalosporins can interfere. In one single-analyser method comparison (Küme et al.; 230 serum samples), Jaffe results were higher than enzymatic results, especially at low creatinine concentrations.

Enzymatic method: more specific, with fewer interferences, and it performed better at low creatinine concentrations in that comparison. Many laboratories now use enzymatic assays calibrated to isotope dilution mass spectrometry (IDMS) reference methods.

How much the method matters varies. In an outpatient comparison (Schmidt 2015; 529 paired results), 5.5% of eGFR results fell on different sides of a clinical decision limit depending on the method, and the authors judged the risk from assay bias to be much smaller than the risk from biological variation.

Why it matters for dosing: Cockcroft-Gault was derived before creatinine measurement was standardized, and renal-function equations are not interchangeable. In a population PK study of 78 elderly patients (Glatard 2015), vancomycin models built on different renal-function equations gave different parameter and AUC estimates, and using an equation other than the one a model was built with could significantly alter predictive performance. Vancomyzer uses the Colin 2019 serum-creatinine covariate as published rather than substituting another renal estimate.

What about muscle mass?

Serum creatinine comes from muscle, so it reflects muscle mass as well as kidney function. In older, sarcopenic or bedbound patients, a low SCr can overstate renal function whichever equation is used: Cockcroft-Gault, CKD-EPI or the Colin 2019 SCr covariate. No creatinine-based equation corrects for this in an individual patient.

Colin 2019 includes age (through an age-standardized reference creatinine and an age-decline factor on clearance), but that describes the average effect of age, not an individual patient’s muscle mass. When the renal estimate is doubtful, measured vancomycin levels entered into the Bayesian fit let the estimate move away from the population prediction.

Vancomyzer uses the SCr you enter and does not round low values up (accepted range 0.1–10 mg/dL). In a single-center retrospective study of 245 patients aged 65 and older (Bukhari 2024), dosing with SCr rounded up to 1 mg/dL was less accurate than dosing with the actual SCr.

The calculator shows an enhanced-monitoring advisory for patients older than 65 and, when the bedbound option is selected, a warning when SCr is below 0.7 mg/dL. Review any renal estimate you consider unreliable, and obtain levels early.

What does Colin 2019 use instead of Cockcroft-Gault?

Age, total body weight and serum creatinine are used directly in a two-compartment model, without first calculating creatinine clearance. FDecline describes the fall in clearance with age; FSCR describes the effect of serum creatinine relative to an age-standardized reference:

CL (L/h) = 5.31 × (WT/70)^0.75 × FMat × FDecline × FSCR
FDecline = 1 / (1 + (PMA/61.6)^2.24)
FSCR = exp(−0.649 × (SCr − SCRstd)), SCr in mg/dL

Source data: Pooled population analysis of data from 14 studies (2,554 individuals), from neonates to elderly adults.

Covariates in the published final model that Vancomyzer does not apply: • Hematological malignancy (+29.4% CL in the published model): not captured as an input. • Heel-prick sampling (neonatal): not applicable to adult venous sampling.

Full equations, parameter values and a typical-adult reference check are on the Equations & derivations page.

Colin PJ, et al. Vancomycin pharmacokinetics throughout life: results from a pooled population analysis and evaluation of current dosing recommendations. Clin Pharmacokinet. 2019;58(6):767-780.

What about IBW — why does traditional dosing require it and why does Vancomyzer not?

In traditional vancomycin dosing, determining the dose requires answering a question that has no single correct answer: which body weight do you use?

Three options are used in clinical practice, each requiring its own calculation:

Total body weight (TBW): the patient’s actual weight. Simple, but TBW-based dosing in traditional (non-model) protocols can produce supratherapeutic levels in obese patients.

Ideal body weight (IBW), Devine formula: the weight a patient “should” be, based on height and sex.

Males:   50 kg + 2.3 kg per inch over 60 inches
Females: 45.5 kg + 2.3 kg per inch over 60 inches

This requires height, which Cockcroft-Gault does not use, and IBW alone can underestimate dose requirements in obese patients.

Adjusted body weight (AdjBW): IBW + 0.4 × (TBW − IBW). Some institutional protocols use it when actual body weight exceeds IBW by more than 30%.

The practical problem: which weight to use varies between institutions, depends on a reliably documented height, and adds a manual step on top of the CrCl estimate. For obese adults, the 2020 ASHP/IDSA/PIDS/SIDP guideline suggests loading doses of 20–25 mg/kg actual body weight (maximum 3,000 mg), maintenance doses usually no higher than 4,500 mg/day, and early monitoring of levels.

How Vancomyzer handles body size: Colin 2019 uses total body weight directly for every adult at every BMI (CL and Q scale with (weight/70)^0.75; V1 and V2 with weight/70). No IBW, AdjBW or height is needed for the calculation, and no other model takes over at any BMI. Measured levels, when entered, individualize the estimate through the Bayesian fit.

Height is still worth entering so BMI can be assessed. At BMI ≥ 40 kg/m², an advisory notes that published evaluation of Colin 2019 at that body size is limited and recommends early vancomycin levels; fat-free mass and alternative creatinine-clearance estimates are shown for information only and do not change the calculation.

How has Colin 2019 performed in independent evaluations?

Vancomyzer has not yet been validated in real patients. Its equations are checked against published values and synthetic test cases; external validation with patient data is planned. The studies below evaluated the published Colin 2019 model, not Vancomyzer itself.

• Heus 2022 (three Belgian hospitals; 169 non-ICU general-ward patients on continuous-infusion vancomycin; 923 samples): Colin 2019 had the second-best predictive performance of 23 published models, after the Okada model. Vancomyzer models intermittent infusion, not continuous infusion. • Aljutayli 2022 (McGill University Health Centre; single-center retrospective data from 116 adults): transferability diagnostics suggested Colin 2019 and a model by Yamamoto et al. were the two of seven literature models best suited to the local data. The authors note that these diagnostics were not strong predictors of predictive performance. • Colin 2021: External evaluation in 49 obese adults (15 with BMI of 40 or more). Colin 2019 had the lowest a-priori imprecision and the best a-posteriori bias and imprecision among the models compared; the cohort is small. • Patanwala 2022 (188 critically ill adults; 466 AUC estimates): Colin 2019, Goti 2018 and Thomson 2009 placed the AUC in the same category (below, within or above 400–600 mg·h/L) for 48% of estimates, so model choice can change dosing decisions in the ICU.

Results depend on the population, infusion method and sampling design, and none of these studies establishes accuracy for every patient. Use measured levels to individualize dosing.

Has Vancomyzer itself been validated in patients?

Vancomyzer has not yet been validated in real patients. Its equations are checked against published values and synthetic test cases; external validation with patient data is planned.

Evidence to date is developer-run: reproduction of published literature cases, synthetic simulation, a synthetic cross-check against Tucuxi, an independent reference calculation of the equations (including loading-dose schedules), and a synthetic check of the uncertainty band's coverage. These checks test whether the equations are implemented as intended; they do not show how accurately Vancomyzer predicts levels in real patients.

The shaded area on the concentration–time graph is a 90% credible band. It shows the middle 90% of concentrations from 400 simulated sets of pharmacokinetic values, using the population estimates before blood levels are entered and updated estimates afterward. It reflects uncertainty in those model estimates but excludes measurement error, so it is not a range for predicting a future blood test result. The calculator explains when it cannot estimate a band reliably. The band’s reliability in patients has not yet been established.

Vancomyzer™ is designed to meet the criteria for non-device clinical decision support in section 520(o)(1)(E) of the Federal Food, Drug, and Cosmetic Act (added by section 3060 of the 21st Century Cures Act). It has not been cleared, approved or otherwise reviewed by the FDA. It is intended for licensed healthcare professionals, who must independently review the basis for each recommendation.

Does Vancomyzer calculate CrCl anywhere?

Not for the dosing calculation. Serum creatinine is used directly (mg/dL) as the Colin 2019 renal covariate: FSCR = exp(−0.649 × (SCr − SCRstd)), where SCRstd is the age-standardized reference creatinine. Cockcroft-Gault does not enter this population prior; after a fit to measured levels, the calculator caps fitted clearance at twice the estimated CrCl.

Cockcroft-Gault estimates appear only in advisories: one can flag possible augmented renal clearance, and at BMI ≥ 40 kg/m² fat-free mass and alternative creatinine-clearance estimates are shown for information only. None of these changes the clearance estimate.

What is fat-free mass (FFM), and does Vancomyzer use it?

Fat-free mass is the part of body weight that is not adipose tissue: muscle, bone, organs and water. The Janmahasatian 2005 equations estimate it from weight, height and sex:

FFM (male)   = (9270 × TBW) / (6680 + 216 × BMI)
FFM (female) = (9270 × TBW) / (8780 + 244 × BMI)

Vancomyzer does not use FFM in its calculation. Colin 2019 scales clearance and volumes with total body weight at every BMI. At BMI ≥ 40 kg/m², FFM is shown for information only.

Open the calculator Evidence and methods