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As regards vancomycin plasma monitoring in patients with MERSA, Should we still rely on peak/trough approach (OR peak only, trough only) for dose optimization? For the trend of target AUC use in vancomycin dose optimization, how many samples are required and their sampling time?
I appreciate your reply!
Ehab S. ELDesoky
Professor of pharmacology
Faculty of Medicine
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A Practice guidelines for therapeutic monitoring of vancomycin treatment for Staphylococcus aureus infection in adult patients were reviewed by an expert panel of the Infectious Diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists (Clin Infect Dis. 2009 Nov 1;49(9):1465). For a summary, you can visit this website http://www.nelm.nhs.uk/en/NeLM-Area/News/2009---July/22/Updated-US-practice-guidelines-for-vancomycin-monitoring-/
Khalid M Alkharfy
College of Pharmacy
King Saud University
Riyadh, Saudi Arabia
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The following message was posted to: PharmPK
Dear Ehab, Khalid, and all:
The recommendations of the expert panel of all these societies is
rather disappointing. Initial vanco doses should be based of the target
trough you want to achieve, individualized to the patient's weight and renal
Why should trough levels be obtained so late, after the 4th dose? Do
these experts really think you have to wait for a steady state before
getting serum levels, leaving the patient at risk until that time? That is
extremely naive and is based on obsolete knowledge and the old approach of
linear regression on the logs of the serum concentrations. There is NO
reason any more to wait for a steady state, any more than there is any
reason to wait until the distribution is the drug is complete after a dose.
Start getting your levels with the first dose, usually a peak and a trough,
to see what is happening to the patient.
Target trough concentrations of 10 are OK, but more and more bugs
are getting resistant, and the therapeutic task is more and more to suppress
the emergence of resistant bugs. Because of this, target troughs of 15 and
even occasionally 20 are recommended for certain individual patients (as all
therapy should be individualized). This also means that our therapy should
become maximally efficient, with the most bang for the dose.
Now, what happens to the peaks as these doses are increased to hit
the higher trough targets? Does no one wish to know what they are? It seems
not, according to these experts.
Let us start with a 65 year old patient, 70 in tall and weighing 70
kg, who has a serum creatinine of 1.0. Let us develop a vancomycin regimen
for him to hit a target trough of 15 ug/ml, giving the drug over 1 hr, q 12
h. If you use our population model for vanco, developed by Dr. Agneta Hurst
several years ago, the ideal dose is a loading dose of 1929 mg, followed by
978 mg, then 908. and then generally by 832 mg infused over 1 hr, q 12 h, or
1600 mg/day. The AUC after a week is 3667 units. Peak vanco concentrations
are about 50, to have a 12 hr trough of 15. Why do we need all that AUC
Vanco is not a concentration dependent drug, and it is relatively
easy in most cases to have a trough of 15 be about 7.5 times the MIC. Higher
concentrations, as at the peak and thereafter for the first 3-4 hrs offer
little in the way of kill, but contribute lots to the development of
toxicity. Note the high AUC of 3667 units.
Now let's make like Wysocky a number of years ago, when he showed
that continuous IV vanco did as well as intermittent, but greatly reduced
the dose needed to get the target concentration. He used 24 hr continuous
infusions. For the same patient, the ideal dose is now only 1469 mg,
followed by 1050 mg/day thereafter, with an AUC for the same week of 2239
However, Wysocky had a problem. He did not get the desired
concentrations until after 24 hours. What to do?
Use a loading dose. Begin with a 1 hr infusion designed to hit your
target at that time. Then follow with another infusion for 5 hours, for
example. Now you are 6 hrs into the regimen. Finish off the first day with
an 18 hr infusion, then follow with 24 hr infusions daily after that. The
regimen is 350 mg over the first hour, then 500 mg for the next 5 hours,
then 1000 mg for the next 18 hrs and 1000 mg q 24 h continuously after that.
The total AUC is 2280 units.
Monitor this regimen with a level at 6 hrs, then at 24 hrs, then at
the end of some later infusion. If the level should be 9/10 of your target,
just infuse 10/9 of what you did before. Very easy.
I have seen 2 patients with agranulocytosis felt by many to be due
to vanco toxicity. They had it infused over 1 hr q 12 h. Maybe if they had
had it continuously, then might not have had the high peaks we all seem to
forget about, and maybe their toxicity might have been less severe. If we
need to be more aggressive with our vanco, then let's for sure try to be
most efficient in the way we give it.
It takes software to do this job of individualizing dosage regimens
for such patients. Our new MM-USCPACK software uses nonparametric population
models which permit Multiple Model dosage design which develops regimens
specifically tailored to hit selected specific targets with maximal
precision (minimum expected weighted squared error). This software can be
evaluated by downloading it from our web site
then we will give you access to download it.
Very best regards,
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