### A vancomycin case study

"Hindsight, unlike pharmacokinetics, is an exact science"

This is a very old vancomycin case from my files (from the days when we used to draw peaks and troughs). Regardless, this case highlights vancomycin's unpredictable pharmacokinetics and also serves to illustrate some of the pitfalls of vancomycin dosing.

This patient was an 86 year old female nursing home patient who was being treated for a staph infection of a knee prosthesis. Her weight was 64.3 kg, height 165 cm, and serum creatinine 0.9 mg%.

Dates Dose given Date levels drawn Peak Trough
11/24 to 11/30 1g Q 12 hrs 11/29 44.1 29.7
11/30 to 12/2 500mg Q 12 hrs 12/2 28.1 22.6
12/2 to 12/10 500mg Q 24 hrs 12/6 17.4 9.8
12/10 15.6 7.8
12/10 to 12/16 1g Q 24 hrs 12/15 13.5 3.1
12/16 to 12/25 1g Q 18 hrs 12/20 28.0 15.6
12/25 33.1 17.7

Some practical lessons to be taken from this case:

1. Dose it right from the start

With 20/20 hindsight it is apparent that the patient was likely overdosed from the start. She had a normal serum creatinine, so she was given a normal dose. It is well documented that renal function declines with age without a change in serum creatinine. Therefore an 86 year old is unlikely to have the same renal function as a younger patient. This patient's calculated creatinine clearance was 40 ml/min. Based on an estimated half-life of 14 hours, a dose of 1g (15.5 mg/kg) every 18 hours may have been a better starting dose.

2. Draw serum levels at steady-state

After a dose change the clinician ordered a serum level "around the fifth dose". There is nothing magic about the fifth dose, instead, serum levels should be drawn at steady-state (approximately four times the half-life). Before ordering levels, one should attempt to estimate half-life and time to steady-state. Definitive conclusions are not possible with pre-steady state levels.

3. Evaluate serum levels critically

It is likely that the high trough level on 12/2 was not a true reflection of the dose because it is completely out of context with the empiric model. We must be cautious when evaluating serum levels. Nursing may administer the dose incorrectly, pharmacy may prepare the dose incorrectly, the phlebotomist may draw the level incorrectly or the laboratory may analyze it incorrectly. When serum levels are so out of context, consider ordering another set of levels before making a drastic dose change.

4. Avoid drastic dose changes

The patient was prescribed 2g/day then 1g/day then 500mg/day then back up to 1g/day. Large dose changes may cause "see-saw" serum levels which are nearly impossible to evaluate, leading to dose chasing. Instead, if the levels are high, estimate the half-life and hold the next dose long enough to allow the trough level to drop down to normal. Then decrease the maintenance dose, but don't make a 100% change. The high trough level on 12/2 was likely a holdover from the original dosing regimen, the dose should have been held to allow the trough to fall to WNL, followed by a modest change in dose.

5. Be aware of accumulation

The last two sets of levels seem to indicate accumulation of vancomycin. There are recent data to suggest that prolonged treatment with vancomycin (>10 days) may result in a decline in the drug's clearance despite stable renal function.

1. Bauer, Larry A. Applied Clinical Pharmacokinetics 3rd edition. McGraw-Hill. 2014.

2. Burton M, Shaw L, Schentag J, Evans W (eds): Applied Pharmacokinetics and Pharmacodynamics, 4th edition. San Francisco, CA. Applied Therapeutics, 2005.

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