- Dosing aminoglycosides and vancomycin requires consideration of the patient's size, infection site and severity, organism resistance, hydration, and many other variables.
- The goal is to administer the right dose at the appropriate frequency to eradicate bacteria without harming the patient by staying within the "therapeutic window."
- Dosing intervals depend on renal clearance, with younger healthy patients receiving more frequent doses and older or renally impaired patients receiving less frequent doses.
- When calculating renal clearance and antibiotic doses, it may be prudent to "fudge" or conservatively adjust values for vulnerable patients.
2. Part 1
- dosing considerations -
“All drugs are controlled poisons”.
“Drugs don’t have dosages…
……patients have dosages….”.
3. Goldilocks Principle
Goldilocks principle states that
something must fall within certain
margins, as opposed to reaching
extremes. When the effects of the
principle are observed, it is known
as the Goldilocks effect.
4. Dosing objective:
Hit the therapeutic window
> Too much = toxicity.
> Right dose: eradicate the
bacteria without injuring the
patient.
> Too little = ineffective.
6. Dosing our pts is problematic
Lack of experience/practice on part of
prescribers, nursing staff and pharmacists
in dosing aminoglycosides & vancomycin.
Patients difficult to assess, remote to both
prescriber & pharmacy staff.
Delay in lab results. We’re not 24/7.
Inherently difficult population to dose
(elderly, bedridden, other potentially
nephrotoxic medications).
7. The dose?
Dosage based predominantly on:
Size of patient
Site of infection
Severity of infection
Resistance of organism
Hydration status of patient
…and 163 other variables…
10. The interval?
Dosing interval based on:
Clearance – the speed at which
the body eliminates the drug
(predominantly renal, with a
small amount of clearance from
the liver)
11. Younger patients who
are otherwise
healthy?
Think shorter dosing
intervals (more
frequent dosing,
i.e., Q4H,Q6H, Q8H).
12. Elderly patients and
patients with renal
insufficiency?
Think longer dosing
intervals (less frequent
dosing, i.e., q12h,
q24h, q48h, q72h)…
13. Quick review of dosing
concepts…..
Dose?
Big patients =
big doses
Little patients =
little doses
Interval?
Younger and
otherwise healthy
patients = more
frequent dosing.
Older, elderly patients
and patients with
renal insufficiency =
less frequent dosing.
14. Serum Creatinine – it’s just a number.
Before you put the numbers in the calculator
think about the pt.
If your patient:
- has a stable renal function SCr/UOP AND
- is within the age range (18-65 years) AND
- is reasonably well nourished/hydrated AND
- doesn’t have renal disease (i.e., not
diabetic, no diuretics, good urine output, etc.)
The calculated answer may be reasonably
close to actual clearance.
15. CrCl: which equation??
Simplified 4-variable MDRD study formula?
CKD-EPI equation?
Cockcroft-Gault based on:
CG - Total Body Weight?
CG - Ideal Body Weight?
CG - Adjusted Body Weight? – use this one….
16. Fudge factor(s)?
→ If the reported SCr is < 1 mg/dL and
the patient is:
Is older than 65 years of age and/or
Is sedentary/bedridden, paralysis
and/or
Has poor nutritional status and/or
Has poor urine output
17. Fudge factor(s)
→ Consider using “1 mg/dL” in your
calculations and/or
→“Lowballing” the dose, i.e.,
- if the recommended peak level for the
condition is 8-10 mcg/ml, consider using 6-8
mcg/ml in your calculations.
- if the recommended trough level for the
condition is <1 mcg/ml, consider using 0.3-
0.5 mcg/ml in your calculations.
18. Why fudge the numbers?
For patients:
- who are elderly (>65 years).
- who have diminished muscle mass
(bedridden, paralysis, malnourished,
who are on diuretics, who are volume
overloaded, etc.), the calculated CrCl
tend to overestimate the actual
clearance.
19. Fudging will give a more
conservative dose
Using a larger than true SCr number will
result in a lower calculated CrCl
(slower clearance).
Fudging will give you a lower dose
and/or a longer dosing interval.