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The following message was posted to: PharmPK
Hello,
I have a question regarding aminoglycosides and endocarditis.
We have a few patients that must be placed in an infusion center due
to insurance issues to treat their endocarditis.
Is there any literature (or thoughts) supporting the use of extended
interval aminoglycosides as possible synergy.
(Typically, these patients are in the center for one dose, once a
day. This rules out the q12h or q8h infusions.)
Any help is appreciated.
Thanks.
Nathan Skorodin, PharmD
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We discourage pulse dosing of aminoglycosides for gram positive synergy at
our institution. I believe this is because the post antibiotic effect is not
significant in the vegetation nidus. See Bates and Nahata, Annals of
Pharmacotherapy 1994 vol 28:757-765 (If your physicians like Sanford's
Guide, point out that it clearly states "not once-daily dosing" with its
gentamicin dosing recommendations for endocarditis).
Tim Gendron
Clinical Coordinator
Naval Medical Center Pharmacy
27 Effingham Street
Portsmouth, VA 23708
(757) 953-0252
rtgendron.-a-.mar.med.navy.mil
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Nathan,
A recent case report and a review article in Annals of Pharmacotherapy
suggest that there may be a role for once-daily aminoglycoside therapy in
gram-positive endocarditis. However, results from studies that have been
published so far remain controversial, and indicate the need for larger more
controlled trials which resolve issues regarding dose and clinical monitoring.
References:
1) Tam, V.H., Preston, S.L., Briceland, L.L., Once-daily aminoglycoside in
the treatment of gram-postive endocarditis, The Annals of Pharmacotherapy
1999; 33:600-606
2) Tam, V.H. et al., Once-daily aminoglycoside in the treatment of
Enterococcus faecalis endocarditis: case report and review, Pharmacotherapy
2000;20:1116-1119
Mike Leibold, PharmD, RPh
ML11439.at.goodnet.com
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The following message was posted to: PharmPK
Nathan,
A recent case report and a review article in Annals of Pharmacotherapy
suggest that there may be a role for once-daily aminoglycoside therapy in
gram-positive endocarditis. However, results from studies that have been
published so far remain controversial, and indicate the need for larger more
controlled trials which resolve issues regarding dose and clinical monitoring.
References:
1) Tam, V.H., Preston, S.L., Briceland, L.L., Once-daily aminoglycoside in
the treatment of positive endocarditis, The Annals of Pharmacotherapy
1999; 33:600-606
2) Tam, V.H. et al., Once-daily aminoglycoside in the treatment of
Entocarditis faecalis endocarditis: case report and review, Pharmacotherapy
2000;20:1116-1119
Mike Leibold, PharmD, RPh
ML11439.-at-.goodnet.com
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Dear Nathan:
With respect to endocarditis, one can compute the diffusion
of drug into a porous spherical object which might resemble an
endocardial vegetation. Arnold Bayer and Donald Crowell did this for
experimental endocarditis and obtained a diffusion coefficient for
amikacin. We have used such a model in the USC*PACK programs to
compute possible diffusion into such vegetations, when they are
bathed in blood, so that you can present them with the serum
concentration profile of a patient receiving the drug. In addition,
one can use a Zhi model to compute, with some skepticism, the effect
of the regimen on the relative number of organisms present, when
presented either with a serum concentration profile, or a profile
from the center of a vegetation, for example. While not totally
realistic, it provides a pretty good "worst cade scenario" for
evaluating the effectiveness of a regimen. It would be really nice if
more work could be done to get more information about drug
concentrations in vegetations at various times after a dose.
Both the diffusion and the effect models are present in the
USC*PACK software, and it is interesting to see what appears to
happen with various regimens under various circumstances. These
models can also be used to gain an impression of the effectiveness of
a regimen on a bug either in the bloodstream, in a peripheral
nonserum compartment, or in a vegetation of a stated diameter with a
stated diffusion coefficient.
You can go to our web site (see below) and download demo
software, and examine these questions. I would be interested in your
comments about all this.
Very best regards,
Roger Jelliffe
Roger W. Jelliffe, M.D. Professor of Medicine, USC
USC Laboratory of Applied Pharmacokinetics
2250 Alcazar St, Los Angeles CA 90033, USA
Phone (323)442-1300, fax (323)442-1302, email= jelliffe.-at-.hsc.usc.edu
Our web site= http://www.usc.edu/hsc/lab_apk
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