Pharmacokinetic Dosing
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Aminoglycoside-Vancomycin Dosing
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Welcome to the updated version. We added
some of the functionality from the advanced
version and improved the reporting section.
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Patient-Specific Data
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Patient Name:
Location:
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Age:
Sex:  Serum Creatinine:
Height:
Weight:
Clearance
method:
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Drug Selection, Levels, and Drug-specific PK Parameters:
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Select Drug:
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Desired Peak:
mcg/ml
Desired Trough:
mcg/ml |
Volume of distribution:
L/kg
Usual range: aminoglycosides: 0.25 - 0.35.
Vanco: 0.65 - 0.9
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Infusion time (ti):
Additional Info
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New option based on input from clinicians - general assumption,
adjusted body weight may be used in the morbidly obese patients
receiving vancomycin: Historically actual or total
is used in all cases.
Use
Adjusted body weight or
Use Actual
(total) weight for vanco dosing (default value) |
Amputations (Optional Field)
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Loading Dose - Aminoglycosides
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(optional)
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(optional) |
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Selecting the infusion time |
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Infusion time (ti) |
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Sample recommendations |
| Aminoglycosides:
(All
doses) |
0.5 |
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Vancomycin
(0 - 500mg/ 0.5 ) |
0.5 |
| 501 - 1250 mg |
1 |
| 1251 -1750 mg |
1.5 - 2.5 |
| 1751 - 2250 mg |
2.5 - 3 |
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Sample recommendations for peak / trough concentrations |
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(Review levels)
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Gentamicin /Tobramycin
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Amikacin
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| 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 |
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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
400 in most
patients if the MIC is
1 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 400 is
not achievable with conventional dosing methods if the
vancomycin MIC is
2 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
1 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.)"
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Background information |
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Background information
(Equations listed are calculated by the program)
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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.
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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.
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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)
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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
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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
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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
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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)
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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)
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References
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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. |
