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We have recently introduce a new discussion format aimed at integrating the
varied opinions of the participants concerning a given topic into a
"consensus document", which may be published for the benefit of
professionals, educators, and students.
The first topic has been chosen; it is the "once-daily dosing" of
aminoglycosides, and I have been asked to be the coordinator of the
discussion. To launch the discussion, the coordinator first prepares and
posts a initial document to be thoroughly dissected and discussed by you to
help the coordinator prepare the final consensus document for publication.
However, before I prepare the initial document, I would like us to better
define our primary objectives, i.e., the main issues that should be
emphasized. The reason is simple - we would like to bring the relevant
issues into focus and contribute new and useful insights; I do not think
that we should aim to write another review article. During the last five
years, over a hundred articles addressed directly or indirectly this topic.
These included reports on original randomized clinical trials, in vitro
studies, animal studies, accounts of clinical experience, meta-analyses,
review articles, book chapters, and newsletters. Here are a few good reviews:
1- Barclay ML, Begg EJ, Hinckling KG. What is the evidence for once daily
aminoglycoside therapy? Clin Pharamcokinet 1994; 27:32-48
2- Gilbert DN. Aminoglycosides. In Mandel GL, Bennett JE, Dolin R.
Principles and Practice of Infectious Diseases. 4th ed. 1995 Churchill
3- Preston SL, Briceland LL. Single Daily Dosing of Aminoglycosides.
Pharmacotherapy 1995; 15:297-316.
The "once-daily" or "single-daily" or "pulse" dosing of
aminoglycosides was first used by Labovitz in 1974 and rediscovered in the
late 1980s. It gained popularity worldwide year after year. A survey
conducted in the USA in 1994 by Schumock and co-workers (Pharmacotherapy
1995, 15:201-209) estimated that in the USA over 25% of hospitals of 400
beds or larger used the qd dosing routinely. Currently many centers are
adopting to the "once-daily aminoglycosides" as their standard practice.
However, we have no solid, updated information concerning:
1. the relative number of institutions/ hospitals that have adopted this
dosing method as their standard (preferred) method. In the USA, the adoption
process usually involves the "Pharmacy and Therapeutics" committee.
2. the "official" guidelines for its use (dose, conditions excluded,
monitoring criteria, etc.).
I believe that we should first make a good effort to gather this type of
information. Our group (PharmPK) and our medium (the InterNet) are best
suited for this task. So please check the hospitals in your town and forward
the above information to me along with a very brief description of each
hospital (size, type of care, etc). My e-mail address is:
nanaizi.aaa.frontiernet.net If you would like to mail printed material (e.g.,
dosing guidelines) my mailing address is:
Dr. Anaizi (Box 638), Univ of Rochester Medical Center. Rochester, NY 14642
In addition, please let me know what you think should be the main focus of
our consensus document.
Ciao, Bye, Addios, ...
University of Rochester Medical Center
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The important questions which need to be answered are:
CAN once-daily dosing of aminoglycosides be done successfully?
SHOULD once-daily dosing of aminoglycosides be done?
How often will deviation from the methods (i.e., patients selected,
duration of therapy, etc.) described in the primary literature be necessary
when this method is adopted in a given institution?
What role doses serum concentration monitoring play? What, if any,
serum concentrations should be obtained? What are "therapeutic" concentrations?
In patients with reduced CrCl, should the daily dose be reduced, or
the interval lengthened?
Should patients with infections of different severity ("mild",
"moderate", "severe") receive different maximal daily doses?
Good luck. SCE
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At 11:17 AM 7/10/96 -0500, you wrote:
>PharmPK - Discussions about Pharmacokinetics
> Pharmacodynamics and related topics
>The important questions which need to be answered are:
> CAN once-daily dosing of aminoglycosides be done successfully?
> SHOULD once-daily dosing of aminoglycosides be done?
>Good luck. SCE
Some observations, perhaps an answer in the bunch... Once daily
aminoglycoside dosing is currently being done successfully at several
institutions in our state. The starting dose is 5mg/kg q24h. A trough is
drawn 2 to 3 hours before the next dose. This gives time to the attending
MD or clinical pharmacist to access the timing of the next dose. Peaks are
drawn 12 to 14 hours after the dose (mid-point).
Different bugs require different peaks to do the job. The literature is
plentiful of high peaks (10-12) getting maximum penetration and the low
troughs (0-.2) giving the bugs a false sense of security and dropping their
guard. Thats the easiest way to put it.
We don't do this in pediatrics. Docs won't hear of it and I agree. I
have a hard time convincing them to give 2.5mg/kg as a loading dose. Also
with kids who have a CrCl of >130ml/min we would have to give 7 to 9 mg/kg
for the effect to even last 24 hours. A second hard sell. Not one I'm
willing to engage in.
There is plenty of literature out there. Most of it was reviewed here and
on the PharmUK list and a couple on the Hospital US list in the past six months.
ODAD is an idea that will either sell in your hospital now or sell later.
Either way we still have to monitor to stop them from cooking kidneys.
Robert Aucoin RPh
Peds Clinical Pharmacist
OLOLRMC Baton Rouge, LA
Robert G. Aucoin RPh
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