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Pharmacokinetic Dosing

Aminoglycoside-Vancomycin Dosing

<<  Link to other Dosing Calculators >> A fellow clinician (Nathan Fewel, PharmD, BCPS), created a quick tool that can be used to quickly generate an empiric regimen for vancomycin while on the floors with just a few data points.  Additional info can be found here.
Patient Name: Location:  
 Select drug:     - Program Hints - 
Need dosing information for once daily dosing? 
Age:      Weight:      Gender
SCR:     Height:
Desired peak:    Desired trough:  Infusion time: hours
Volume of distribution:   L/kgselect VD
Usual range: aminoglycosides: 0.25 - 0.35         Vancomycin: 0.65 - 0.9

Program Hints

Selecting the infusion time
 
Infusion time (ti)
Sample recommendations
Aminoglycosides:   (All doses) 0.5
Vancomycin   
(0 - 500mg/  0.5 )
0.5
501 - 1250 mg 1
1251 -1750 mg 1.5 - 2.5
1751 - 2250 mg 2.5 - 3
Sample recommendations for peak / trough concentrations

(Review levels) Gentamicin /Tobramycin Amikacin
Infection Site Peak Trough Peak Trough
Abdominal 6-7 <1 25-30 4-6
Cystitis 4-5 <1 20-25 4-6
Endocarditis 4-12 <1.5 25-30 <8
Osteomyelitis 6-7 <1 25-30 4-6
Pneumonia 8-10 <1.5 25-30 <8
Pyelonephritis 6-7 <1 25-30 4-6
Sepsis 7-8 <1 25-30 4-6
Soft tissue 6-7 <1 20-25 <6
Synergy 5-6 <1 20-25 4-6
Wound Infections 6-7 <1 25-30 <6
Vancomycin - Target trough levels??
Rybak M, Lomaestro B, Rotschafer JC, et al. (2009). "Therapeutic monitoring of vancomycin in adult patients: A consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists". American Journal of Health-System Pharmacy 66 (1): 82–98.

Direct quotes from this reference (Rybak et al.):


"Further, data derived from more recent studies appear to suggest that vancomycin has little potential for nephrotoxicity or ototoxicity when used at conventional dosages (e.g., 1 g every 12 hours [15 mg/kg every 12 hours]), unless it is used concomitantly with known nephrotoxic drugs or at very high dosages."

Recommended TDM Parameters- Optimal monitoring parameter: "Trough serum vancomycin concentrations are the most accurate and practical method"

Timing of monitoring: "Troughs should be obtained just prior to the next dose at steady-state conditions (approximately after the fourth dose)."

Optimal trough concentration (see also Optimal trough concentration—complicated infections) : "Minimum serum vancomycin trough concentrations should always be maintained above 10 mg/L to avoid development of resistance. For a pathogen with an MIC of 1 mg/L, the minimum trough concentration would have to be at least 15 mg/L to generate the target AUC:MIC of 400."

Criteria for monitoring: "Data do not support using peak serum vancomycin concentrations to monitor for nephrotoxicity."

"Trough monitoring is recommended for patients receiving aggressive dosing (i.e., to achieve sustained trough levels of 15–20 mg/L) and all patients at high risk of nephrotoxicity (e.g., patients receiving concurrent nephrotoxins). Monitoring is also recommended for patients with unstable (i.e., deteriorating or significantly improving) renal function and those receiving prolonged courses of therapy (more than three to five days)."

Summary and recommendations
"Vancomycin dosages should be calculated on ABW. For obese patients, initial dosing can be based on ABW and then adjusted based on serum vancomycin concentrations to achieve therapeutic levels. Continuous infusion regimens are unlikely to substantially improve patient outcome when compared with intermittent dosing. (Level of evidence = II, grade of recommendation = A.)"

"Trough serum vancomycin concentrations are the most accurate and practical method for monitoring vancomycin effectiveness. Trough concentrations should be obtained just before the next dose at steadystate conditions. (Level of evidence = II, grade of recommendation = B.) (Note: Steady-state achievement is variable but occurs approximately after the fourth dose.)"

"Based on evidence suggesting that S. aureus exposure to trough serum vancomycin concentrations of <10 mg/L can produce strains with VISAlike characteristics, it is recommended that trough serum vancomycin concentrations always be maintained above 10 mg/L to avoid development of resistance. (Level of evidence = III, grade of recommendation = B.)"

"Based on the potential to improve penetration, increase the probability of optimal target serum vancomycin concentrations, and improve clinical outcomes for complicated infections such as bacteremia, endocarditis, osteomyelitis, meningitis, and hospitalacquired pneumonia caused by S. aureus, total trough serum vancomycin concentrations of 15–20 mg/L are recommended. Trough serum vancomycin concentrations in that range should achieve an AUC/MIC of geq400 in most patients if the MIC is leq1 mg/L. (Level of evidence = III, grade of recommendation = B.) In order to achieve rapid attainment of this target concentration for seriously ill patients, a loading dose of 25–30 mg/kg (based on ABW) can be considered. (Level of evidence = III, grade of recommendation = B.) A targeted AUC/MIC of geq 400 is not achievable with conventional dosing methods if the vancomycin MIC is geq2 mg/L in a patient with normal renal function (i.e., CLcr of 70–100 mL/min). Therefore, alternative therapies should be considered. 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 leq1 mg/L. It should be noted that currently available nomograms were not developed to achieve these targeted endpoints. Individual pharmacokinetic adjustments and verification of serum target achievement are recommended. When individual doses exceed 1 g (i.e., 1.5 and 2 g), the infusion period should be extended to 1.5–2 hours. (Level of evidence = III, grade of recommendation = B.)"


"Available evidence does not support monitoring peak serum vancomycin concentrations to decrease the frequency of nephrotoxicity. (Level of evidence = I, grade of recommendation = A.) Monitoring of trough serum vancomycin concentrations to reduce nephrotoxicity is best suited to patients receiving aggressive dosing targeted to produce sustained trough drug concentrations of 15–20 mg/L or who are at high risk of toxicity, such as patients receiving concurrent nephrotoxins. (Level of evidence = III, grade of recommendation = B.) Monitoring is also recommended for patients with unstable renal function (either deteriorating or significantly improving) and those receiving prolonged courses of therapy (over three to five days). (Level of evidence = II, grade of recommendation = B.) All patients receiving prolonged courses of vancomycin should have at least one steady-state trough concentration obtained (approximately after the fourth dose). Frequent monitoring (more than a single trough concentration before the fourth dose) for short-course therapy (less than five days) or for lower-intensity dosing (targeted to attain trough serum vancomycin concentrations below 15 mg/L) is not recommended. (Level of evidence = II, grade of recommendation = B.)"






M. Goodwin, E. Ashley. Vancomycin: can we teach the mainstay of therapy for gram-positives new tricks?   Special to Infectious Disease News. February 2006.
http://www.infectiousdiseasenews.com/200602/frameset.asp?article=pharmconsult.asp
Accessed: December 15th, 2006
"Independent of the reason, many clinicians are now targeting higher troughs for vancomycin (from 15 to 20 mcg/mL), especially when treating more deep-seated infections (ie, meningitis, endocarditis, osteomyelitis), in which vancomycin penetration may also be an issue."
-----
"The recent pneumonia guidelines, a joint publication from the American Thoracic Society and the Infectious Diseases Society of America (IDSA), advocate targeting higher vancomycin trough concentrations. Vancomycin is a large molecule, and we have known for sometime that penetration into the lung and other infection sites may be difficult. Therefore, increasing the target trough serum concentrations may result in higher pulmonary drug concentrations.  The recommended target vancomycin trough in these guidelines is 15 to 20 mcg/mL. However, there are no specific data to say that troughs more than 15 mcg/mL are associated with improved outcomes over trough levels more than 5 or 10 mcg/mL."   
-----
"Because many clinicians consider the vegetations involved in endocarditis to be relatively difficult to penetrate, the traditional target troughs were 15 to 20 mcg/mL for this infection. The recent guidelines, however, recommend a lower trough concentration of 10 to 15 mcg/mL. As with the pneumonia guidelines, these targets reflect the opinion of the expert panel in the absence of data to document the ideal target."
See link above for the complete article....

L. Briceland. Ask the Experts about Pharmacotherapy - From Medscape Pharmacists. Would You Explain the Current Recommendations for Vancomycin Trough Levels? 
http://www.medscape.com/viewarticle/508120    Accessed: December 15th, 2006
"More recently, recommendations for optimal therapeutic serum concentrations have varied widely: none at all except in select clinical situations[3]; 5-10mcg/mL[2]; 5-15 mcg/mL[4]; and 5-20 mcg/mL.[5] These recommendations have arisen specifically due to the lack of clear evidence for the concentrations needed to maintain therapeutic efficacy and avoid concentration-dependent toxicity[6] and the understanding that vancomycin exerts concentration-independent killing." "Exceeding the minimum inhibitory concentration (MIC) by 4-5 times does not produce further cidality; thus, the ranges cited would provide adequate serum and tissue concentrations to kill most pathogens (in which the MIC is generally less than 2 mcg/mL).[5] The current dosing regimen of 15 mg/kg every 12 hours (in normal renal function) is still employed with the intent of achieving therapeutic troughs (now broadly defined as anywhere between 5-20 mcg/mL)."     See link above for the complete article....
Background information

Background information  (Equations listed are calculated by the program)
Obtain baseline data:
Patient age, sex, height, weight, allergies, diagnosis, infection site, current 
drug therapy, I/O's for past 24 hours, Tmax, WBC with diff, albumin, 
Past medical history, Lab work-up: Scr, Bun, cultures etc.
Estimate Ideal body weight in (kg)
 Males: IBW = 50 kg + 2.3 kg for each inch over 5 feet.
 Females: IBW = 45.5 kg + 2.3 kg for each inch over 5 feet.
If the actual body weight is greater than 25% of the calculated IBW, calculate the adjusted body weight (ABW):            
 ABW = IBW + 0.4(Total body weight - IBW) 
Estimate Creatinine Clearance: (ml/min)
       Cockcroft and Gault equation:
       CrCl = [(140 - age) x IBW] / (Scr x 72)       (x 0.85 for females)
       Note: if the ABW (actual body weight) is less than the IBW use the 
       actual body weight for calculating the CRCL. If the patient is >65yo and 
       creatinine<1,  use 1 to calculate the creatinine clearance
Estimate kel (Elimination rate constant):
  Amikacin /Gentamicin/Tobramycin: Kel = (0.00285 x CrCl) + 0.015
      May also use: (0.003 x CrCl) + 0.01
  Vancomycin: kel = (0.00083 x CRCL)  + 0.0044 (used by program)
        Equation used by the Detroit VA Medical Center: CRCL x 0.0012

     The above equations provide an estimate of the elimination rate
     constant based on population kinetics. The following may decrease
     the usefulness of these equations:
          *Renal failure, CHF, Burn patients, cystic fibrosis, severe
            hypotension, rapidly changing renal function. (Burn victims 
            and patients with cystic fibrosis usually have increased 
            rates of elimination. Patients with CHF or severe hypotension 
            will have decreased rates of elimination due to decreased 
            renal perfusion).
Estimate half-life (T1/2) in hours:
      T1/2 = 0.693 / Kel
Estimate Volume of Distribution (Vd): (Liters)
Aminoglycosides:
    Use IBW unless obese, then use ABW= 0.4 x (TBW-IBW) + IBW
    Vd (Normal) = 0.25 to 0.3 L/kg
Vancomycin
:
    [Use actual body weight in all cases]
    Vd (Normal): 0.6 to 0.7 L/kg 
Select Time of Infusion (ti):
(a) Aminoglycosides: 30 minutes (0.5 hrs)
(b) Vancomycin: 0-500 mg/ 0.5 hrs ; 501 to 1250 mg/ 1 hour ;
        1251 to 1750/ 1.5 hrs ; >1750/ 2 hours
Calculate Dosing Interval (T)    hrs.
    T = Ln (Cmax/Cmin) / kel + ti or estimated T = 3 x T1/2
Calculate Maintenance dose (MD):_____mg.
   MD = [(kel) x (Vd) x (ti) x (Cpeak desired) x (1 - e-kT)] / (1 - e-kti)
     or MD = (Cpeak desired) x Vd (eg: C = D/V, therefore D=C*V)
Calculate Predicted Peak and Trough at Steady State.
          Cmax = [Dose * 1-e-kti] / (kel)(Vd)(ti) 1-e-kT

          Cmin = Cmax * e-k(T-ti)
 

References

1) Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16(1):31-41

2) Davis GA, Chandler MH. Comparison of creatinine clearance estimation methods in patients with trauma. Am J Health-Syst Pharm 1996;53:1028-32.

3) Dawson-Saunders B, Trapp RG. Basic and Clinical Biostatistics. 2nd ed. Norwalk, CT: Appleton & Lange; 1994.

4) Dettli LC. Drug dosage in patients with renal disease. Clin Pharmacol Ther 1974;16:274-80.

5) Drusano LG, Munice HL, Hoopes JM et al. Commonly used methods of estimating creatinine clearance are inadequate for elderly debilitated nursing home patients. J Am Geriatrics Soc 1998;36:437-41.

6) Hailemeskel B, Namanny M, Kurz A. Estimating aminoglycoside dosage requirements in patients with low serum creatinine concentrations. Am J Health-Syst Pharm 1997;54:986-7.

7) Jelliffe RW. Estimation of creatinine clearance when urine cannot be collected. Lancet 1971;1:975-6.

8) Levey AS, Greene T, Kusek JW, et al. A simplified equation to predict glomerular filtration rate from serum creatinine (Abstr) J Am Soc Nephrol 2000;(11):155A

9) Levey AS, Greene T, Schluchter MD, et al. Glomerular filtration rate measurements in clinical trials. Modification of Diet in Renal Disease Study Group and the Diabetes Control and Complications Trial Research Group. J Am Soc Nephrol 1993;4(5):1159-71

10) Levey AS. Assessing the effectiveness of therapy to prevent the progression of renal disease. Am J Kidney Dis 1993;22(1):207-14

11) Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;130(6):461-70

12) Rhodes RS, Sims PJ, Culbertson VL et al. Accuracy of creatinine clearance estimates in geriatric males with elevated serum creatinine clearance. J Geriatric Drug Ther 1991;5:31-45.

13) Smythe M, Hoffman J, Kizy K et al. Estimating creatinine clearance in elderly patients with low serum creatinine concentrations. Am J Hosp Pharm 1994;51:189-204.

Disclaimer

All calculations must be confirmed before use. The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material.PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.   Read the disclaimer
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