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Hints
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Selecting the infusion time
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|
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 |
| 1751 - 2250 mg |
2 |
|
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Sample recommendations for peak / trough
concentrations
|
|
(Review levels)
|
Gentamicin
/
Tobramycin
|
Amikacin
|
Vancomycin
|
| Infection
Site |
Peak |
Trough |
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 |
30-40 |
5-15 |
| Osteomyelitis |
6-7 |
<1 |
25-30 |
4-6 |
30-40 |
5-20 |
| Pneumonia |
8-10 |
<1.5 |
25-30 |
<8 |
30-40 |
5-20 |
| Pyelonephritis |
6-7 |
<1 |
25-30 |
4-6 |
25-35 |
5-10 |
| Sepsis |
7-8 |
<1 |
25-30 |
4-6 |
25-35 |
5-15 |
| Soft tissue |
6-7 |
<1 |
20-25 |
<6 |
25-35 |
5-10 |
| Synergy |
5-6 |
<1 |
20-25 |
4-6 |
25-35 |
5-10 |
| Wound Infections |
6-7 |
<1 |
25-30 |
<6 |
25-35 |
5-10 |
| Vancomycin
- Target trough levels?? |
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 µg/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 µg/mL.
However, there are no specific data to say that troughs more
than 15 µg/mL are associated with improved outcomes over trough
levels more than 5 or 10 µg/mL."
-----
"Because many clinicians consider the vegetations involved
in endocarditis to be relatively difficult to penetrate, the
traditional target troughs were 15 to 20 µg/mL for this
infection. The recent guidelines, however, recommend a lower
trough concentration of 10 to 15 µg/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.... |
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Background information
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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 unless obese (> 30% over
IBW)-then
use adjusted
body weight = 0.4(TBW- IBW) + IBW.]
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)
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