# Vancomycin Initial Dosing

# Dose Adjustments by Trough

# Dose Adjustments by Two Levels

# Peak after single dose, and Time from C1 to goal trough

**Description of Calculators**

- Vancomycin initial dosing
- Pharmacokinetic (PK) parameters volume of distribution (V) and vancomycin clearance (CLvanco) are estimated using the Bauer method.
^{1} - First, ideal body weight (IBW) is determined:
- IBW for men = 50 kg + 2.3(height – 60 inches)
- IBW for women = 45.5 kg + 2.3(height – 60 inches)

- Next, patient data is evaluated for obesity, defined as: actual BW/ IBW ≥ 130%. The calculator automatically uses different ways of estimating V and creatinine clearance (CrCl) depending on obesity status.
- For non-obese patients:
- Volume of distribution (V) = 0.70 L/kg of actual BW
- V ranges from about 0.5 to 1.0 L/kg in non-obese patients.

- CrCl is calculated using the Cockcroft-Gault equation
^{2}- CrCl = [(140 – age) actual BW] / (72 x SCr) *0.85 if female

- Volume of distribution (V) = 0.70 L/kg of actual BW
- For obese patients:
- V = 0.70 L/kg of IBW
- The Bauer method uses IBW to calculate V in obese patients because V does not significantly change with obesity. Obese patients have kidney hypertrophy which increases glomerular filtration rate and vancomycin clearance.
^{1}

- The Bauer method uses IBW to calculate V in obese patients because V does not significantly change with obesity. Obese patients have kidney hypertrophy which increases glomerular filtration rate and vancomycin clearance.
- CrCl is calculated by the Salazar-Corcoran equation
^{3}- CrCl for men = (137 – age) [(0.285 x weight(kg)) + (12.1 x height(meters
^{2}))] / (51 x SCr) - CrCl for women = (146 – age) [(0.287 x weight(kg)) + (9.74 x height(meters
^{2})] / (60 x SCr)

- CrCl for men = (137 – age) [(0.285 x weight(kg)) + (12.1 x height(meters

- V = 0.70 L/kg of IBW
- Vancomycin clearance (CLvanco) = [(0.695 x CrCl/ actual BW) + 0.05] (actual BW x 0.06)
- An elimination rate constant (K) is calculated based on vancomycin clearance and V:
- K = CLvanco/ V

- Half-life (T
_{1/2}): T_{1/2}= 0.693/ K - Dosing interval (T): T = Ln (Peak/ Trough)/ K
- Dose = (Peak*V)(1 – e
^{–K*T})- CrCl is capped at 160 mL/min, which results in initial doses being capped at 1500 mg every 8 hours in most cases. Consider reserving empiric maintenance doses of 1500 mg q8h for patients <55 years old, >100 kg, with CrCl >140 mL/min. For non-obese patients consider limiting empiric maintenance doses to about 17.5 mg/kg q8h.

- Peak = Dose [1 – e
^{–K*ti}] / [(K*V*ti) (1 – e^{-K*T})]- Goal peaks: less than about 45 mcg/mL.

- Infusion time (ti): ti = 1000 mg/hr
- 1000 mg/hr is generally considered the maximum infusion rate. Symptoms of red man syndrome (flushing, pruritus, erythema, rash) are often related to infusion rate. If any symptoms occur, stop the infusion and contact a physician. For mild symptoms, physicians can contact pharmacy to slow the infusion rate to 750 mg/hr (12.5 mg/min), and/or premedicate with antihistamines to prevent recurrence.
- If vancomycin is ordered by a pharmacy consult, consider attaching a nursing text order to the consult to improve communication and management of infusion reactions.

- Trough = Peak*e
^{-K (T – ti)}- For patients with normal renal function, troughs are usually drawn prior to the 4th or 5th dose or within 36 hours from the loading dose. For patients with chronic kidney disease, troughs are drawn within 48 hours from the loading dose; waiting for the 4th dose may delay the time to reach goal.

- Loading dose = V * Peak
_{SS}- Loading doses help to decrease the time to attain effective vancomycin concentrations.
- This equation is based upon administration of the loading dose as the first dose on the maintenance dosing schedule.
- Adjust loading doses as needed so maintenance doses may be scheduled around convenient (morning) lab times.
- Loading doses are capped at 2,500 mg.

- The ratio of the 24-hour area under the concentration-time curve to the MIC of an organism:
- AUC
_{24}/MIC = [(total daily dose)/ CLvanco]/ MIC- Where CLvanco = V*K

- AUC

- Pharmacokinetic (PK) parameters volume of distribution (V) and vancomycin clearance (CLvanco) are estimated using the Bauer method.
- Dose adjustments based on a trough
- First, K is estimated using this equation:
- K = Ln [((dose/ V) + Trough)/ Trough]/ [(time to trough + T)/2]

- Next, iteration is used to improve precision of K so that K can be used in the following equation to calculate the measured trough
^{4}:- Trough = [(dose/V)* e
^{-K*(time to trough)}]/ (1 – e^{-K*T})- Use the population estimate for V from the initial dosing calculations.

- Trough = [(dose/V)* e
- After K is calculated, measured troughs can be extrapolated:
- Trough drawn early:
- Extrapolated trough = Measured trough *e
^{-K*t}

- Extrapolated trough = Measured trough *e
- Trough drawn late:
- Extrapolated trough = Measured trough/ e
^{-K*t}

- Extrapolated trough = Measured trough/ e

- Trough drawn early:

- First, K is estimated using this equation:
- Dose adjustments based on two levels: K = Ln (C1/C2)/ ∆t
- This calculator may be used to calculate a dose based on two random levels, as long as no vancomycin is given between the two levels.
- Since vancomycin peaks are not measured in clinical practice, use the population estimate for V from the initial dosing calculations. For an example of calculating V, see the aminoglycoside dose adjustment calculator.

- AUC
_{24}/MIC = [(total daily dose)/ (V*K)]/ MIC- Besides this classical equation, other methods include the Moise-Broder equation and the log-linear trapezoidal rule.
^{1,5} - Using a steady-state trough to calculate the AUC
_{24 }is the most practical way of estimating vancomycin exposure. - Troughs do not correlate well with the AUC
_{24}, because troughs largely depend on dosing intervals whereas the AUC_{24}is calculated based on total daily dose and clearance. For example, a trough may be similar for a dose of 2000 mg every 12 hours compared to a dose of 1000 mg every 8 hours, but the peak and AUC_{24}are much higher for the dose of 2000 mg every 12 hours. Acute kidney injury (AKI) is a well-known potential adverse effect of vancomycin. An AUC_{24}of 700 mg*hr/L represents a conservative upper level of safe vancomycin exposure with minimal risk of nephrotoxicity.^{7} - Goal AUC
_{24}/MIC ratios have not been determined for coag-negative staph or Enterococcus which more often have higher vancomycin MICs compared to*S. aureus*. An AUC_{24}/MIC ratio of at least 400 has been suggested to treat*S. aureus*infections such as bacteremia, pneumonia, and complicated skin and soft tissue infections.^{5-7}When a vancomycin MIC = 1 mg/L, a trough of 13 to 15 mcg/mL is often adequate to achieve the goal AUC_{24}/MIC ratio. When a vancomycin MIC = 0.5 mg/L, using a goal trough of at least 10 mcg/mL may help to prevent selection of vancomycin-intermediate*S. aureus*(VISA). For hard to penetrate*S. aureus*infections like CNS infections, endocarditis, and osteomyelitis, using higher doses to target a trough range of 15-20 mcg/mL may improve drug delivery at the infection site, even with an MIC of 0.5 mg/L. When*S. aureus*has a vancomycin MIC ≥ 2 mg/L, targeting an AUC_{24}/MIC ratio >400 begins to noticeably increase toxicity, so providers should consider switching to a different antibiotic.

- Besides this classical equation, other methods include the Moise-Broder equation and the log-linear trapezoidal rule.
- Time from C1 to C2
- C2 = C1*e
^{-K*t} - This calculator may be used to determine the number of hours from a supra-therapeutic vancomycin level (C1) to a therapeutic level (C2).

- C2 = C1*e
- Peak after a single dose
- ∆C = Dose/ V
- This calculator estimates a peak after a single dose, taking into account a vancomycin serum level prior to the dose.

**Symbol Key:**

- AUC
_{24}/MIC = The ratio of the 24-hour area under the concentration-time curve to the MIC of an organism - C1 and C2: C1 occurs before C2. Sometimes C1 and C2 are referred to as Cmax and Cmin, but the terms Cmax and Cmin usually refer to true peak and true trough levels.
- CLvanco = Vancomycin clearance
- CrCl = Creatinine clearance
- IBW = Ideal body weight
- K = Elimination rate constant
- PK = Pharmacokinetic
- SCr = Serum creatinine
- T
_{1/2}= half-life - ti = infusion time (hrs)
- T = dosing interval (hrs)
- V = Volume of distribution

**References:**

- Bauer LA. Vancomycin. In: Applied Clinical Pharmacokinetics, 3rd Ed. New York: McGraw Hill, 2014:197-213,241-243.
- Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine.
*Nephron**.*1976;16(1):31-41 - Salazar DE, Corcoran GB: Predicting creatinine clearance and renal drug clearance in obese patients from estimated fat-free body mass.
*Am J Med*. 1988;84:1053–1060. - Ambrose PJ, Winter ME. In: Winter ME. Basic clinical pharmacokinetics, 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2004: Equation on page 470.
- Moise-Broder PA, Forrest A, Birmingham MC, et al. Pharmacodynamics of vancomycin and other antimicrobials in patients with
*Staphylococcus aureus*lower respiratory tract infections.*Clin Pharmacokinet.*2004;43:925–942 - Prybylski, JP. Vancomycin trough concentration as a predictor of clinical outcomes in patients with
*Staphylococcus aureus*bacteremia: A meta-analysis of observational studies.*Pharmacotherapy.*2015;35(10):889–898 - Neely MN, Youn G, Jones B,
*et al.*Are vancomycin trough concentrations adequate for optimal dosing?*Antimicrob Agents Chemother.*2014;58(1):309-16. - Fewel NP. Comparison of open-access vancomycin dosing websites.
*J Clin Pharm Ther.*2016 Oct.

**Downloads:**

Vancomycin-Monitoring-Form.doc

Vancomycin-Monitoring-Form.pdf

**Inappropriate Populations:** This calculator is NOT appropriate for the following patient populations or those who require a higher degree of clinical judgment: < 18 years old, unstable renal function, severe renal impairment (CrCl <25 mL/min), hemodialysis, or hematological malignancies.

**IDMS:** The Cockcroft-Gault and Salazar-Corcoran equations have not been updated for use with the serum creatinine methods traceable to IDMS. Use with IDMS-traceable serum creatinine methods may overestimate renal function; use with caution.

**Disclaimer:** The author and contributors make no claims of the accuracy of the information contained herein; these suggested doses are not a substitute for clinical judgment. The persons involved in the preparation of this program shall not be liable for the use of or reliance upon this material.