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Hello,
What do you think of 19 for a Vancomycin trough on a 51 year old man
with Creatinine of 1.2? We are treating Septic Arthritis.. I don't
know what the MIC is... He is 90 kg. I was thinking we should extend
the interval. The man had a dose of Vanco 1.4 Gm q12h to get that
trough. He is having no symptoms of nephrotoxicity, and is on no other
nephrotoxic agents.
Cindy Cloud, RPh
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Cindy,
A trough of 19 indicates that accumulation /may/ be occurring. But I
wouldnt recheck troughs more than weekly unless renal function worsens.
Lakshmi
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The following message was posted to: PharmPK
How big is the guy? Is the patient at steady state? What are you worried
about, 19 is a great trough for bad infections.
Glenn
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Definite accumulation. Assuming that the value is mg/litre and not
mmol/litre.
Our practice here (for better or for worse, but shaped by med
malpractice experiences - our MDs were external consultants for med-mal
cases, and found that many resulted from not doing levels, so insurance
paid out the claim) is to do pre and post levels on these cases, and
adjust dosing and/or intervals based on the levels. There are others
who say no levels needed unless on vanco a long time, or at risk for
nephrotoxicity.
Greg Soon
Greg Soon
Pharmacist-Critical Care
Peterborough Regional Health Centre
Peterborough, ON, Canada K9J 7C6
tel: (705) 743-2121 x.3196 or x.3254
fax: (705) 876-5072
email: gsoon.-a-.sympatico.ca
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The following message was posted to: PharmPK
Cindy,
I would adjust the dose for a trough in the neighborhood of 12. I am not
comfortable with 19 in a patient with a Cr of 1.2.
I have never seen a MIC of 5 to warrant such a high level. Also, I would
recheck the level in 48 hours. Remember that the vanco level is a more
accurate to measure renal function than Cr. If you really want to find
out
the patients true renal function, draw a peak and trough in the same
interval.
Cr levels are about 72 hours late when it comes to telling you that the
kidneys are fried.
Good luck.... Robert
Robert Aucoin, Pharm D.
Clinical Pharmacy Spec - Peds/PICU
Department of Pharmacy
Our Lady of the Lake RMC
Baton Rouge, La 70809
office: 225-765-7652
fax: 225-765-8221
e-mail: raucoin.-a-.ololrmc.com
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The following message was posted to: PharmPK
1-We don't know if vanc is still accumulating at this point, as we have
not been provided with all the necessary information. For example, if
the patient has recieved 10 doses over the period of 5 days, with a
t1/2 of 10 hours, then 90%+ steady state has been achieved, and this
trough value is relective of a steady state trough value (with a Cmax
of probably 40-45 mcg/mL -- and that isn't remarkable). So, the answer
at this point is that we simply just don't know.
2-Nephrotoxicity is of little concern. Even with Cmax's in the 30s.
WIth the information provided, 1.2 mg/dL for Serum creatinine, is
unimpressive, as it is on the high end of normal. Unless, the patient's
SCr was 0.8 the day before, I wouldn't flinch too much at this SCr of
1.2 mg/dL.
Nephrotoxicity was in relative high incidence when vanc was first
introduced, because of the formulation had much impurities (Mississippi
mud); and over the years has become more and more pure, with the
incidence of nephrotoxicity dropping significantly. the patient may be
at greater risk for nephrotox if they are on concomitant meds that can
affect renal fxn (e.g. aminoglycosides). Just a note, that ototoxicity
probably has had about 25 cases in the past 50 years of use.
Considering that millions of doses of vanc have probably been used,
that almost marginalizes vanc as a causor of ototoxicity.
3-Regardless of legal issues, the use of post (Cmax) concentrations are
arguable. While I prefer to obtain a concentration 2 hrs post dose, and
one just prior to next dose, to extrapolate a true Cmax, this probably
doesn't provide anymore clinical utility than just my own satisfaction.
Toxicities are not associated with high Cmax; and if you have a very
high Cmax (>60-80 mcg/mL), more than likely, you have a very high Cmin
(>30), at which may put at risk for nephrotoxicity.
Glenn
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There exists a lot of controversy about monitoring of vancomycin
troughs. Since the incidence of adverse effects with the current
preparation of the drug is low and there is no clear proof of a
relationship between toxicity and serum levels, most clinicians do not
suggest monitoring vancomycin troughs unless in certain circumstances
that may warrant such monitoring (e.g. rapidly changing renal function,
concurrent therapy with nephrotoxic agents, dialysis, dosing interval >
48h, etc.)
Here are some references that may help:
1. Wilhelm M, Estes L. Vancomycin. Mayo Clin Proc. 1999; 74(9):
928-35.
2. Moellering R. Monitoring Serum Vancomycin Levels: Climbing the
mountain because it is there? Clin Infect Dis. 1994; 18:
544-46. Editorial.
3. Hammett-Stabler C, Johns T. Laboratory guidelines for monitoring
of antimicrobial drugs. Clin Chem. 1998; 44(5): 1129-40.
4. Cantu T, Yamanaka-Yuen N, Lietman P. Serum vancomycin
concentrations: reappraisal of their clinical value. Clin
Infect Dis. 1994; 18: 533-43.
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The following message was posted to: PharmPK
At our institution we shoot for a trough of 5-20, so your trough would
be fine here. We use a 1 g standard dose and adjust interval, except
for hemodialysis patients.
Carol A. Roby, PharmD, MS
Clinical Pharmacist
St. Agnes Hospital
900 Caton Avenue
Baltimore, MD 21229
410-368-3109
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Hi Carol:
You wrote: "...we shoot for a trough of 5-20..."
Could you give us any reference (clinical trial) of this data , please?
Thank you.
Paulo A. Caceres Guido
Pharmacist
Clinical Pharmacokinetic Unit
Hospital de Pediatria GArrahan
Buenos Aires, Argentina
Paulo A. Caceres Guido
Unidad de Farmacocinetica Clinica
Hospital de Pediatria Prof. Dr. Juan P. Garrahan
Combate de los Pozos 1881 - puerta 4232 / 17
Ciudad de Buenos Aires - Argentina - CP: 1245
TE: x-54-11-4308-4300 ext. 1676 FAX: ext.1337
E-mail: pcaceres.-a-.garrahan.gov.ar
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The following message was posted to: PharmPK
Agree with Glenn completely. In addition, if the patient is on
concurrent meds that cause renal toxicity such as aminoglycosides, you
will need to monitor closely. At our institution, we use a trough of
10-15 mcg/ml for regular infection and 15-20 for severe infection such
as neutropenic fever, osteo, endocarditis, and joint infection. For
pneumonia (vent dependent) we aim trough around 20 mcg/ml. Things to
consider are: 1. Is the level steady state?, 2. Are there other agents
on board that may complicate the picture? 3. Is the patient's renal
function changing (Scr)? 4. Was the level drawn at the right time? 5.
Were the vancomycin doses given at the appropriate intervals and at the
right timing?
Linda
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The following message was posted to: PharmPK
Hi Linda:
Do you have clinical trials (as references) which show those target
levels (troughs until
20) as sure and needed?
Paulo
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[Subject Re: Vanco Trough levels - show me the literature]
The following message was posted to: PharmPK
Question to all,
Where are you getting the data for these Vancomycin troughs of 15 - 20?
How is your lab reporting these levels?
What is the MIC of the treated organisms?
What prompts you to believe that you need this level to eradicate the
organisms?
Are you doing Tr:MIC ratios or are you using AUC measurements?
What in the basic pharmacology of Vancomycin has made you decide on
these
high levels?
I am a bit skeptical re: troughs > 10-12 to treat anything. Especially
when
I have seen severe renal toxicity with troughs in the 15 - 20 range on
real
patients.
All this being said, my specialty is Pediatrics and I follow 10 to 15
different patients daily as well as a large ICU population. If the
organism
- usually MRSA - has a MIC of > 2, then we change medication or use
double
coverage with a non-renal toxic drug. I adjust levels to a trough of
10 -
12 and no more.
I have a lot of clinical experience with MRSA pneumonia and find
Vancomycin
to be of little use when the MIC is 2 or greater. We will use it in
combination with Linezolid or Rifampin or Clinda or Nafcillin.
Jerry Schentag... where are you?
My $0.10 American
Thanks.......... Robert
Robert G. Aucoin, Pharm D.
Clinical Pharmacy Spec - Peds/PICU
Department of Pharmacy
Our Lady of the Lake RMC
Baton Rouge, La
Office: 225-765-7652
e-mail: raucoin.-a-.ololrmc.com
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The following message was posted to: PharmPK
There is no final consensus on what trough level is ideal. However,
based on the following literature and our clinicians experiences, we
have changed our lab reference range to 10-15 mcg/ml except for VAP (20
mcg/ml).
1.Zimmerman AE, et al. Association of vancomycin serum concentrations
on the outcome of patients being treated with Gram-positive bacteremia.
Pharmacotherapy 1995;15:85-91. (reduced # of fever days when trough
was > 10 mcg/ml)
2. Mulhern JG, et al. Trough serum vancomycin levels predict the
relapse of gram-positive peritonitis in peritoneal dialysis patients.
Am J Kidney Dis 1995;25:611-5. (no relapse when trough was > 12mcg/ml)
3. Georges H, et al. Pulmonary disposition of vancomycin in
critically ill patients. Eur K Clin Microbiol Infect Dis
1997;16(5):385-8. (suggests trough of 20 mcg/ml correlates with an
Epithelial Lining Fluid level of 2 mcg/ml)
4. American Thoracic Society and the Infectious Diseases Society of
America. Guidelines for the Management of Adults with
Hospital-acquired, Ventilator-associated, and Healthcare-associated
Pneumonia. Am J Respi Crit Care Med 2005;171:388-416. (states high
failure rates with vancomycin related to inadequate dosing. Many
physicians tried to achieve a trough conc. equal of greater than 15
mcg/ml.
Hope this help.
Linda
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The following message was posted to: PharmPK
Hi Linda:
There is not known ideal trough level, but, majority of clinicians use
5 to 10 or 15 in some special cases. Perhaps we need begin trying this
type of schemes, through clinical assays.
Reference of George et al "suggests trough of 20 mcg/ml correlates with
an
Epithelial Lining Fluid level of 2 mcg/ml" but also write that "further
studies are requiered to determine the clinical relevance of these
observations". That is the only clinical trial that you have referenced
with 20 as target level.
Guidelines of American Thoracic Society is something like a review.
With your clinicians experiences, have you made any retrospective (or
prospective) analysis to study renal function parameters (for example)
in VAP patients, when your target is 20 mcg/ml? Or a comparative
between 10 and 20 mcg/ml for example?
Please, don't misinterpret my question. I think that point can be very
interesting and useful, but perhaps we need more important evidence.
Thank you very much
Paulo A. Caceres Guido
Unidad de Farmacocinetica Clinica
Hospital de Pediatria Prof. Dr. Juan P. Garrahan
Combate de los Pozos 1881 - puerta 4232 / 17
Ciudad de Buenos Aires - Argentina - CP: 1245
TE: x-54-11-4308-4300 ext. 1676 FAX: ext.1337
E-mail: pcaceres.-a-.garrahan.gov.ar
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Dear Linda:
About Vancomycin and desirable target serum concentrations.
I have the impression that the common MIC of bugs that Vanco
is used for is about 1.0 ug/ml. Since Vanco is about 1/2 protein
bound, you need 2 total to get 1.0 free. Vanco is not a very
concentration dependent drug, and the kill rate appears to plateau
off after about 5-6 times the MIC, so concentrations of 12 are 6
times the common MIC (this should always be obtained if possible).
Higher peak concentrations are probably not that useful, and may well
constitute an unnecessary exposure of the patient to the drug.
I have seen 2 patients with severe granulocytopenia and
thrombocytopenia felt by everyone here as most probably due to vanco.
They received their vanco q 12 h. Their adverse reactions might well
have been less severe if they had received less drug.
Frequent dosing more often means that peak levels are less,
and also so is the total daily dosage. How can the dosage be made
most efficient? Good kill but minimal toxicity? Wysocki et al had a
good idea of using continuous IV vanco. Their only problem was that
they couldn't get the target concentration until the end of the first
day. However, they didn't use a loading dose. See:
Antimicrobial Agents and Chemotherapy, September 2001, p. 2460-2467,
Vol. 45, No. 9
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.9.2460-2467.2001
Copyright (c) 2001, American Society for Microbiology. All rights
reserved.
Continuous versus Intermittent Infusion of Vancomycin in Severe
Staphylococcal Infections: Prospective Multicenter Randomized Study
Marc Wysocki,1,* Frederique Delatour,2 Francois Faurisson,2 Alain
Rauss, Yves Pean,4 Benoit Misset,5 Frank Thomas,6 Jean-Francois
Timsit,7 Thomas Similowski,8 Herve Mentec,9 Laurence Mier,10 Didier
Dreyfuss,10 and The Study Group
Medico-Surgical Intensive Care Unit1 and Microbiology,4 Institut
Mutualiste Montsouris, Medico-Surgical Intensive Care Unit, Hopital
Saint-Joseph,5 Medico-Surgical Intensive Care Unit, Hopital de
Diaconesses,6 INSERM U132 and Infectious Diseases Critical Care Unit,
7 Hopital Bichat-Claude Bernard, and Respiratory Intensive Care Unit,
Hopital de la Pitie-Salpetriere,8 Paris, Medico-Surgical Intensive
Care Unit, Hopital V. Dupouy, Argenteuil,9 and Medical Intensive Care
Unit, Hopital Louis Mourier, Colombes,10 France
Received 28 June 2000/Returned for modification 2 January 2001/
Accepted 5 June 2001
A continuous infusion of vancomycin (CIV) may provide an alternative
mode of infusion in severe hospital-acquired methicillin-resistant
staphylococcal (MRS) infections. A multicenter, prospective,
randomized study was designed to compare CIV (targeted plateau drug
serum concentrations of 20 to 25 mg/liter) and intermittent infusions
of vancomycin (IIV; targeted trough drug serum concentrations of 10
to 15 mg/liter) in 119 critically ill patients with MRS infections
(bacteremic infections, 35%; pneumonia, 45%). Microbiological and
clinical outcomes, safety, pharmacokinetics, ease of treatment
adjustment, and cost were compared. Microbiological and clinical
outcomes and safety were similar. CIV patients reached the targeted
concentrations faster (36 +/- 31 versus 51 +/- 39 h, P = 0.029) and
fewer samples were required for treatment monitoring than with IIV
patients (7.7 +/- 2.2 versus 11.8 +/- 3.9 per treatment, P < 0.0001).
The variability between patients in both the area under the serum
concentration-time curve (AUC24h) and the daily dose given over 10
days of treatment was lower with CIV than with IIV (variances, 14,621
versus 53,975 mg2/liter2/h2 [P = 0.026] and 414 versus 818 g2 [P =
0.057], respectively). The 10-day treatment cost per patient was $454
+/- 137 in the IIV group and was 23% lower in the CIV group ($321 +/-
81: P < 0.0001). In summary, for comparable efficacy and tolerance,
CIV may be a cost-effective alternative to IIV.
* Corresponding author. Mailing address: Reanimation Polyvalente,
Institut Mutualiste Montsouris, 42 Bd. Jourdan, 75674 Paris Cedex,
France. Phone: 331.56.61.61.79. Fax: 331.56.61.61.99. E-mail:
marc.wysocki.aaa.imm.fr .
Antimicrobial Agents and Chemotherapy, September 2001, p. 2460-2467,
Vol. 45, No. 9
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.9.2460-2467.2001
Copyright (c) 2001, American Society for Microbiology. All rights
reserved.
Now, if we consider a 65 year old man, 70 in tall, 70 kg,
serum creatinine=1.0, and select a trough target goal of 12 ug/ml at
12 hrs after starting a 1 hr infusion q 12 h, our MM-USCPACK software
for maximally precise "multiple model" dosage design, using a 2
compartment model (see www.lapk.org) would suggest a regimen of:
Lastname a Firstname a
Date of birth 07/30/1940 Age 65 BSA 1.87
Gender Male Height 70.00 in Weight 70.00 kg
Drugname Vancomycin Provider LAPK
Planning Future Therapy
Route IV Option 4 - Control Central Compt. Conc. at Chosen Time after
Goal 1 12.00 [ug/mL]
Time 1 12.00 [hours]
ObjFunc 8.2461 AUC 1669.62
Dose #Date Time Dose Dose
AUC Total AUC
[mg] [mg/kg] [ug/
mL] [ug/mL]
1 07/30/05 16:00:00 1543.2963 22.0471
239.98 239.98
2 07/31/05 04:00:00 782.4071 11.1772
211.74 451.72
3 07/31/05 16:00:00 726.5609 10.3794
206.57 658.29
4 08/01/05 04:00:00 700.4957 10.0071
204.08 862.37
5 08/01/05 16:00:00 686.3458 9.8049
202.71 1065.08
6 08/02/05 04:00:00 678.2254 9.6889
201.92 1267.00
7 08/02/05 16:00:00 673.4066 9.6201
201.45 1468.45
8 08/03/05 04:00:00 670.4772 9.5782
201.17 1669.62
Goal # Time [h] Goal WgtAvg Diff
1 12.00 12.00 12.00 0.00
2 24.00 12.00 12.00 0.00
3 36.00 12.00 12.00 0.00
4 48.00 12.00 12.00 0.00
5 60.00 12.00 12.00 0.00
6 72.00 12.00 12.00 0.00
7 84.00 12.00 12.00 0.00
8 96.00 12.00 12.00 0.00
Future Summary (Serum Concentrations)
Central Compartment Peripheral
Compartment
Mean Max Min Last Value Mean
Max Min
23.61 66.32 0.00 12.00 9.07
0.00 6.18
21.54 44.84 12.00 12.00 9.93
6.18 6.61
20.72 42.53 12.00 12.00 10.06
6.61 6.82
20.25 41.44 12.00 12.00 10.14
6.82 6.95
19.95 40.85 12.00 12.00 10.19
6.95 7.02
19.74 40.51 12.00 12.00 10.23
7.02 7.07
19.58 40.31 12.00 12.00 10.25
7.07 7.11
19.38 40.19 12.00 12.00 10.27
7.11 7.13
In this case the total daily dose is a loading dose of 1583
mg, then 782, tapering down to 670 q 12 h. or a bit more than1300 mg
per day, and the total AUC for the first 4 days is 1669.62 ug/ml-days.
On the other hand, you can set a target goal of 12 ug/ml at
2 hours, for example, and then the same again at 4 and 6 hours, and
then follow this with continuous infusions after that. You can go to
our web site and get more info on this general way of computing
dosage regimens specifically with maximum precision (a new feature).
For example, if you again have the same 65 year old. 70 in tall, 70
kg man with a serum creatinine of 1.0, the stepwise but continuous
infusion regimen to hit and keep a target of 12 ug/ml would be:
Planning Future Therapy
Route IV Option 3 - Continous IV Central Compartment
Goal 1 N/A
Time 1 N/A
ObjFunc 5.2591 AUC 1055.39
Dose #Date Time Dose Dose AUC Total
AUC IV Rate
[mg] [mg/kg] [ug/mL] [ug/
mL] [mg/min]
1 07/30/0518:00:00 366.1249 5.2304 10.24
10.24 3.05
2 07/30/0520:00:00 181.7027 2.5958 12.11
22.34 1.51
3 07/30/0522:00:00 129.0215 1.8432 12.35
34.70 1.08
4 07/31/0500:00:00 751.7992 10.7400 195.95
230.65 0.70
5 07/31/0518:00:00 894.8736 12.7839 273.26
503.90 0.62
6 08/01/0518:00:00 864.4431 12.3492 275.42
779.33 0.60
7 08/02/0518:00:00 853.1318 12.1876 276.06
1055.39 0.59
Goal # Time [h] Goal WgtAvg Diff
1 2.00 12.00 12.00 0.00
2 4.00 12.00 12.00 0.00
3 6.00 12.00 12.00 0.00
4 24.00 12.00 12.00 0.00
5 48.00 12.00 12.00 0.00
6 72.00 12.00 12.00 0.00
7 96.01 12.00 12.00 0.00
Future Summary (Serum Concentrations)
Central Compartment Peripheral Compartment
Mean Max Min Last Value Mean Max
Min Last Value
9.83 12.00 0.00 12.00 1.16 1.69 0.00 1.69
10.98 12.00 11.26 12.00 1.88 2.98 1.69 2.98
11.33 12.00 11.73 12.00 2.42 3.68 2.98 3.68
11.48 12.00 11.18 12.00 3.88 4.98 3.68 4.98
11.67 12.00 11.79 12.00 4.82 5.52 5.37 5.52
11.82 12.00 11.97 12.00 5.00 5.59 5.52 5.59
So the infusion is 366 mg over the first 2 hours, then
stepping down to 181mmg for the next 2 hrs, then down again to129mg
for the 3rd 2 hrs, then 751 mg for the remaining 18 hrs of the first
day, and then 894 mg/day, tapering more slowly down to 843 mg/day as
the peripheral compartment continues to equilibrate slowly. In
general. your total daily dose is less than 900 mg/day. The levels
will be about 12 over the entire day, and they will be reached in the
first 2 hrs of therapy, instead of after waiting for 1 day. Total AUC
is 1055 ug/ml-days for the 1st 4 days of the regimen, versus 1669.
You have saved about 1/3 of the dose, with less risk of toxicity, and
also a cost saving, with probably just as good a kill, as Wysocki
showed. The dose and cost saving is even greater when you compare it
to q 24 hr dosing. Monitoring morning levels and adjusting doses is
easy, as the adjustment up or down is simply proportional to the
distance from the target goal.
This is the way we like to pursue vanco therapy. This model-
based, target goal-oriented approach has been shown to be useful both
for outcome and cost effectiveness for aminoglycoside therapy, and
may well be so also for vanco. You might see: van Lent-Evers NA,
Mathot RA, Geus WP, van Hout BA, Vinks AA. Impact of goal-oriented
and model-based clinical pharmacokinetic dosing of aminoglycosides on
clinical outcome: a cost-effectiveness analysis. Ther Drug Monit.
1999; 21(1):63-73.
Very best regards,
Roger Jelliffe
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