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Part 2 – Aminoglycoside &
Vancomycin dosing
 Pharmacy to dose:
- a dose
- a frequency
- monitoring/labs
Basic patient information
Name
Gender
Age
Height
Weight
the patient – information for dosing…
Other essential
information
for initial dosing:
-Site of infection?
-Serum creatinine?
If available:
- Culture & sensitivity?
- Intake & output?
- CBC / WBC?
- Status of patient
- ambulatory? bed bound?
- Nutrition status?
How current/accurate is the
information?
Height and weight.
- Estimated? Measured? Amputation(s)?
- How recent?
Labs.
- when were the labs drawn?
Nutrition status.
- is the patient eating? being fed?
I & O.
- measured? is the patient producing urine?
Once you have as much information
as you need……….
Time to calculate a dose & frequency.
..and remember….
Large patients = large doses
Small patients = small doses
Younger pts = more frequent dosing
Older pts = less frequent dosing
Real patient…….
90 y.o. female – pharmacy to dose
vancomycin x10 days for UTI (?).
SCr 1.36 mg/dL (0.67-1.00)
Height 60”
Weight 94.5 lbs
Real patient…continued…
WBC 5.3 (3.4-10.8)
Urinalysis
Yellow, clear
Protein negative
Nitrite negative
WBC 0-5 (0-5)
Bacteria: few
Urinalysis - microbiology
 Enterococcus species. Abnormal.
Greater than 100,000 CFU per mL.
“Note: this isolate is vancomycin-susceptible.
This information is provided for epidemiological
purposes only: vancomycin is not among the
antibiotics recommended for therapy of urinary
tract infections caused by enterococcus.”
Sensitivities………..
 Antibiotic Result__
Ciprofloxacin S
Levofloxacin S
Nitrofurantoin* S
Penicillin S
Tetracycline R
Vancomycin S
So why are we
using
vancomycin??
...good
question....
Fundamentals of antibiotic stewardship
 Use the antibiotic that is:
- the most narrow spectrum
- least toxic
- least expensive
- doesn’t require monitoring
- has no contraindications for the patient
- screen for true allergies
- screen for potential drug interactions
Myth of the “stronger” antibiotic???
A more expensive, broad spectrum
antibiotic is typically no more effective
than a narrow spectrum antibiotic as
long as (1) the antibiotic is effective
against the organism and (2) is
delivered in therapeutic concentration
to the site of infection.
Before making your recommendation
to change antibiotics..
Get
your
ducks
in
a
row……
Before you call & suggest changing…
 Double check C&S results.
 Make sure the antibiotic is appropriate/indicated for the
infection you are treating.
 Consolidate: if patient is on two antibiotics & you can
use a single antibiotic – think about it.
 Check & question patient allergies (PCN, sulfa, ceph’s,
etc.).
 Check for drug interactions (TMP-SMX & warfarin, etc.)
 Make your suggestion with a dose, route, frequency.
Online calculators and equations
Global R Ph.
Lexicomp
Extended interval dosing of aminoglycosides:
http://ugapharmd.com/calculators/gentldei.htm
Others….
Go slowly be careful…
 Use calculator/equations that are easiest for you.
 Keep mindful of your units (lbs, kg, cm, inches, mg/dL,
mmol/L, etc).
 Be more conservative:
- Elderly pts and/or pts with renal failure
- Pts receiving other potentially nephrotoxic agents
- Malnourished patients
- Pts with poor renal output
- Pts who are dehydrated
Vancomycin nomogram dosing
1) Determine CrCl.
2) If CrCl > 30 mL/min use nomogram to
determine dose and frequency.
3) If CrCl < 30 mL/min, use conventional
dosing or online calculator.
Vancomycin nomogram..easy peasy..
Vancomycin online calculator
Global R Ph
 Name
 Location
 Pick antibiotic
 Age
 Weight
 Gender
 SCr
 Height
 Desired peak
 Desired trough
 Infusion time
 Volume of distribution
Aminoglycosides: 0.25 – 0.35 L/kg
Vancomycin 0.65-0.9 L/kg
What if you don’t have labs?
vancomycin
 If recent labs aren’t available and it is necessary
to begin therapy before they are available,
consider…
For vancomycin:
25-30 mg/kg, one-dose loading dose (max of 2
grams) for seriously ill patients.
Adjust dose and determine frequency when labs
available.
Alternative……
Go to online calculator, put in the known values of:
- height
- weight
- desired peak
- desired trough
- use “1” for Serum creatinine value
- ORDER ONLY A ONE INITIAL LOADING DOSE based on this calculation.
For example: if the calculator suggests:
Vancomycin 1250 mg IV q12h will give you prospective peak and
trough levels of 35 and 16 mcg/ml, order ONLY 1250 mg as a loading
dose, then calculate subsequent dosing when labs are back.
Online calculator for aminoglycosides
For conventional or traditional
dosing, use the calculator
basically the same way.
Pick levels based on type of
infection.
Target levels for indication…
Gentamicin/
Tobramycin
Amikacin
Infection Site Peak Trough Peak Trough
Abdominal 6-7 <1 25-30 4-6
Cystitis 4-5 <1 20-25 4-6
Endocarditis 4-12 <1.5 25-30 <8
Osteomyelitis 6-7 <1 25-30 4-6
Pneumonia 8-10 <1.5 25-30 <8
Pyelonephritis 6-7 <1 25-30 4-6
Sepsis 7-8 <1 25-30 4-6
Soft tissue 6-7 <1 20-25 <6
Synergy 5-6 <1 20-25 4-6
Wound Infections 6-7 <1 25-30 <6
What if you don’t have labs?
aminoglycosides
 Consider a one-time loading dose &
adjusting dose when labs are known.
Give dose which is adequate to achieve
peak level for the infection you are
treating.
Probably the easiest thing to do….
 Go to online calculator, put in the known values of:
- height
- weight
- desired peak
- desired trough
- use “1” for Serum creatinine value
- ORDER ONLY A ONE INITIAL LOADING DOSE based on this calculation.
For example: if the calculator suggests:
Gentamicin 200 mg IV q12h will give you prospective peak and
trough levels of 8 and 0.7 mcg/ml, order ONLY 200 mg as a loading
dose, then calculate subsequent dosing when labs are back.
When labs come back…….
 Adjust dose, interval based on newly acquired labs…
 If you calculate a new dose close to the one you started
with, just solider on…
For example:
If you gave vancomycin 1.25 grams to start with, and the
newly calculated dose is vancomycin 1 gm iv q12h, just
continue with vancomycin 1 gm iv q12h beginning approximately
12 hours after first dose.
If you need to give a smaller dose, use the calculator to
determine when the patient would trough out, and continue
with smaller dose.
Aminoglycosides dosing options:
(gentamicin,tobramycin,amikacin)
Extended interval (“once daily”)
nomogram dosing?
or
Traditional dosing?
Aminoglycoside
nomogram dosing
 Hartford nomogram: 7 mg/kg ABW q24h,
q36h or q48h – recommend not using it.
 IF patient appropriate for nomogram dosing,
use 5 mg/kg ABW and only with 24 hour
dosing interval.
What about “once daily” or
“extended interval dosing”?
 For our patient population, I would advise:
(1) using only the 5 mg/kg nomogram and
(2) only in those patients with calculated
CrCl greater than 60 mL/min.
 I would not order “once daily” dosing
without having a recent SCr.
University of Georgia online calculator
 http://ugapharmd.com/calculators/gentldei.htm
 Aminoglycoside Extended Interval Dosing
 __Gentamicin/Tobramycin 5mg/kg
 __Gentamicin/Tobramycin 7mg/kg
 __Amikacin 15mg/kg
 Patient height: ______
 Patient weight:______
 Male________ Female______
 Calculator will determine dose: _________ mg
Nomogram dosing…be careful…
 Advantages of nomogram dosing:
- Determine and administer dose.
- Random (single) level 6-14 hours after
beginning of infusion.
- Determine interval based on level (not peak
and trough levels).
- Less frequent dosing.
 - Disadvantages:
- Total dose is recognized as potential risk factor for
toxicity.
5 mg/kg dosing nomogram
 q24h & q36h interval dosing (no q48h dosing).
- q24h dosing is simple, manageable.
- q36h dosing problematic – suggest avoid.
- up to the nursing/secretarial staff to figure out
administration times. RN has to give it. Some facilities
don’t have RN evening/night staff.
- potential for dosing errors (missed, late or early
administration of doses) greater with awkward intervals (i.e.,
q16h, q18h, q36h, etc.).
Bottom line: if patient doesn’t fit into q24h hour interval
(estimated CrCl of 60 or greater), don’t use nomogram.
Some patients need more than
“standard” monitoring.
*Be cautious, especially with elderly
pts, pts with renal insufficiency and
pts with changing renal function.
Consider drawing levels early, i.e.,
trough prior to 2nd dose or 3rd dose,
etc.
Nomograms included on website:
Amikacin nomogram
Levels?
 Policy: “aminoglycosides and vancomycin - trough drawn
immediately before the fourth dose”.
 Don’t assume it’s going to be done.
 Write the order & be specific, especially with timing(s).
 For pts with rapid clearance, trough prior to 4th dose, peak after
4th dose may be ok.
 For pts with slow clearances, consider drawing levels around
3rd dose.
 For pts with very slow clearances and/or changing renal
function, consider drawing trough before 2nd dose.
Please be careful….calculators
don’t think, they only give answers….
 Units – make sure you’re entering correctly?
- kg or lbs?
- cm or inches?
- non-US calculators may use different units for SCr
(umol/L)
 Get someone else to independently verify your
answers.
 Use convenient dosing intervals, i.e.,
Every 6, 8, 12, 24, 48, 72 hour dosing intervals.
Be judicious, but give adequate dose..
With reasonable dosing and appropriate monitoring, the
consequences of an untreated infection are usually worse
the toxicities of most antibiotics, even aminoglycosides
and vancomycin….
Aminoglycoside toxicity does not usually occur before 5
days. Vancomycin, usually longer…..
Monitoring/Vancomycin
 Trough immediately prior (30 minutes) to 4th
dose or earlier if patient has impaired renal
function.
 Monitor vancomycin trough and serum
creatinine levels at least weekly if renal
function stable and 2-3 times weekly for
patients with unstable renal function.
Toxicity/Vancomycin
 Nephrotoxicity most common.
- Usually reversible, especially if caught early.
Monitoring/Aminoglycosides
 Conventional dosing: IV: trough prior (30 minutes) to 4th
dose, peak (30 minutes) after infusion of the 4th dose. IM:
trough 30 minutes before injection, peak 1 hour after IM
injection.
 Extended interval dosing: random aminoglycoside level 6
to 14 hours after the end on infusion.
 Monitor antibiotic and serum creatinine levels at least
weekly if renal function stable and 2-3 times weekly for
patients with unstable renal function.
Toxicity/Aminoglycosides
 Aminoglycoside toxicity usually does not occur within the first 5
days of therapy….
- be careful… usually does not always equate to never….
 Nephrotoxicity most common:
- usually acute tubular necrosis.
- if caught early, usually reversible.
 Ototoxicity less common:
- Auditory (Higher frequencies. May progress to lower
frequencies).
- Vestiublar (loss of balance, headache, nausea, nystagmus,
etc).
- Rarely reversible.
When you get labs/levels back….
Figure out where you are…. Before jumping to conclusions..
 Doses given?
 Doses given on time?
 Sample (peak/trough) drawn
appropriately?
 If something looks amiss, it probably
is..
 Multiple places for errors to occur.
Screen vanc/AG orders for
over/under-dosage…..
 Assume dose ordered is inappropriate.
 Obtain information the same as if pharmacy was
consulted for dosing, even if we’re not dosing.
 Make sure dose is appropriate for indication for which it is
prescribed.
 Notify appropriate staff (physician, nursing, etc.) if dose is
outside of reasonable prospective levels.
 Insure appropriate monitoring labs are ordered.
Part 2 - Aminoglycoside  Vancomycin dosing

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Part 2 - Aminoglycoside Vancomycin dosing

  • 1. Part 2 – Aminoglycoside & Vancomycin dosing  Pharmacy to dose: - a dose - a frequency - monitoring/labs
  • 3. the patient – information for dosing… Other essential information for initial dosing: -Site of infection? -Serum creatinine? If available: - Culture & sensitivity? - Intake & output? - CBC / WBC? - Status of patient - ambulatory? bed bound? - Nutrition status?
  • 4. How current/accurate is the information? Height and weight. - Estimated? Measured? Amputation(s)? - How recent? Labs. - when were the labs drawn? Nutrition status. - is the patient eating? being fed? I & O. - measured? is the patient producing urine?
  • 5. Once you have as much information as you need………. Time to calculate a dose & frequency. ..and remember…. Large patients = large doses Small patients = small doses Younger pts = more frequent dosing Older pts = less frequent dosing
  • 6. Real patient……. 90 y.o. female – pharmacy to dose vancomycin x10 days for UTI (?). SCr 1.36 mg/dL (0.67-1.00) Height 60” Weight 94.5 lbs
  • 7. Real patient…continued… WBC 5.3 (3.4-10.8) Urinalysis Yellow, clear Protein negative Nitrite negative WBC 0-5 (0-5) Bacteria: few
  • 8. Urinalysis - microbiology  Enterococcus species. Abnormal. Greater than 100,000 CFU per mL. “Note: this isolate is vancomycin-susceptible. This information is provided for epidemiological purposes only: vancomycin is not among the antibiotics recommended for therapy of urinary tract infections caused by enterococcus.”
  • 9. Sensitivities………..  Antibiotic Result__ Ciprofloxacin S Levofloxacin S Nitrofurantoin* S Penicillin S Tetracycline R Vancomycin S
  • 10. So why are we using vancomycin?? ...good question....
  • 11. Fundamentals of antibiotic stewardship  Use the antibiotic that is: - the most narrow spectrum - least toxic - least expensive - doesn’t require monitoring - has no contraindications for the patient - screen for true allergies - screen for potential drug interactions
  • 12. Myth of the “stronger” antibiotic??? A more expensive, broad spectrum antibiotic is typically no more effective than a narrow spectrum antibiotic as long as (1) the antibiotic is effective against the organism and (2) is delivered in therapeutic concentration to the site of infection.
  • 13. Before making your recommendation to change antibiotics.. Get your ducks in a row……
  • 14. Before you call & suggest changing…  Double check C&S results.  Make sure the antibiotic is appropriate/indicated for the infection you are treating.  Consolidate: if patient is on two antibiotics & you can use a single antibiotic – think about it.  Check & question patient allergies (PCN, sulfa, ceph’s, etc.).  Check for drug interactions (TMP-SMX & warfarin, etc.)  Make your suggestion with a dose, route, frequency.
  • 15. Online calculators and equations Global R Ph. Lexicomp Extended interval dosing of aminoglycosides: http://ugapharmd.com/calculators/gentldei.htm Others….
  • 16. Go slowly be careful…  Use calculator/equations that are easiest for you.  Keep mindful of your units (lbs, kg, cm, inches, mg/dL, mmol/L, etc).  Be more conservative: - Elderly pts and/or pts with renal failure - Pts receiving other potentially nephrotoxic agents - Malnourished patients - Pts with poor renal output - Pts who are dehydrated
  • 17. Vancomycin nomogram dosing 1) Determine CrCl. 2) If CrCl > 30 mL/min use nomogram to determine dose and frequency. 3) If CrCl < 30 mL/min, use conventional dosing or online calculator.
  • 19. Vancomycin online calculator Global R Ph  Name  Location  Pick antibiotic  Age  Weight  Gender  SCr  Height  Desired peak  Desired trough  Infusion time  Volume of distribution Aminoglycosides: 0.25 – 0.35 L/kg Vancomycin 0.65-0.9 L/kg
  • 20. What if you don’t have labs? vancomycin  If recent labs aren’t available and it is necessary to begin therapy before they are available, consider… For vancomycin: 25-30 mg/kg, one-dose loading dose (max of 2 grams) for seriously ill patients. Adjust dose and determine frequency when labs available.
  • 21. Alternative…… Go to online calculator, put in the known values of: - height - weight - desired peak - desired trough - use “1” for Serum creatinine value - ORDER ONLY A ONE INITIAL LOADING DOSE based on this calculation. For example: if the calculator suggests: Vancomycin 1250 mg IV q12h will give you prospective peak and trough levels of 35 and 16 mcg/ml, order ONLY 1250 mg as a loading dose, then calculate subsequent dosing when labs are back.
  • 22. Online calculator for aminoglycosides For conventional or traditional dosing, use the calculator basically the same way. Pick levels based on type of infection.
  • 23. Target levels for indication… Gentamicin/ Tobramycin Amikacin Infection Site Peak Trough Peak Trough Abdominal 6-7 <1 25-30 4-6 Cystitis 4-5 <1 20-25 4-6 Endocarditis 4-12 <1.5 25-30 <8 Osteomyelitis 6-7 <1 25-30 4-6 Pneumonia 8-10 <1.5 25-30 <8 Pyelonephritis 6-7 <1 25-30 4-6 Sepsis 7-8 <1 25-30 4-6 Soft tissue 6-7 <1 20-25 <6 Synergy 5-6 <1 20-25 4-6 Wound Infections 6-7 <1 25-30 <6
  • 24. What if you don’t have labs? aminoglycosides  Consider a one-time loading dose & adjusting dose when labs are known. Give dose which is adequate to achieve peak level for the infection you are treating.
  • 25. Probably the easiest thing to do….  Go to online calculator, put in the known values of: - height - weight - desired peak - desired trough - use “1” for Serum creatinine value - ORDER ONLY A ONE INITIAL LOADING DOSE based on this calculation. For example: if the calculator suggests: Gentamicin 200 mg IV q12h will give you prospective peak and trough levels of 8 and 0.7 mcg/ml, order ONLY 200 mg as a loading dose, then calculate subsequent dosing when labs are back.
  • 26. When labs come back…….  Adjust dose, interval based on newly acquired labs…  If you calculate a new dose close to the one you started with, just solider on… For example: If you gave vancomycin 1.25 grams to start with, and the newly calculated dose is vancomycin 1 gm iv q12h, just continue with vancomycin 1 gm iv q12h beginning approximately 12 hours after first dose. If you need to give a smaller dose, use the calculator to determine when the patient would trough out, and continue with smaller dose.
  • 27. Aminoglycosides dosing options: (gentamicin,tobramycin,amikacin) Extended interval (“once daily”) nomogram dosing? or Traditional dosing?
  • 28. Aminoglycoside nomogram dosing  Hartford nomogram: 7 mg/kg ABW q24h, q36h or q48h – recommend not using it.  IF patient appropriate for nomogram dosing, use 5 mg/kg ABW and only with 24 hour dosing interval.
  • 29. What about “once daily” or “extended interval dosing”?  For our patient population, I would advise: (1) using only the 5 mg/kg nomogram and (2) only in those patients with calculated CrCl greater than 60 mL/min.  I would not order “once daily” dosing without having a recent SCr.
  • 30. University of Georgia online calculator  http://ugapharmd.com/calculators/gentldei.htm  Aminoglycoside Extended Interval Dosing  __Gentamicin/Tobramycin 5mg/kg  __Gentamicin/Tobramycin 7mg/kg  __Amikacin 15mg/kg  Patient height: ______  Patient weight:______  Male________ Female______  Calculator will determine dose: _________ mg
  • 31. Nomogram dosing…be careful…  Advantages of nomogram dosing: - Determine and administer dose. - Random (single) level 6-14 hours after beginning of infusion. - Determine interval based on level (not peak and trough levels). - Less frequent dosing.  - Disadvantages: - Total dose is recognized as potential risk factor for toxicity.
  • 32. 5 mg/kg dosing nomogram  q24h & q36h interval dosing (no q48h dosing). - q24h dosing is simple, manageable. - q36h dosing problematic – suggest avoid. - up to the nursing/secretarial staff to figure out administration times. RN has to give it. Some facilities don’t have RN evening/night staff. - potential for dosing errors (missed, late or early administration of doses) greater with awkward intervals (i.e., q16h, q18h, q36h, etc.). Bottom line: if patient doesn’t fit into q24h hour interval (estimated CrCl of 60 or greater), don’t use nomogram.
  • 33. Some patients need more than “standard” monitoring. *Be cautious, especially with elderly pts, pts with renal insufficiency and pts with changing renal function. Consider drawing levels early, i.e., trough prior to 2nd dose or 3rd dose, etc.
  • 36. Levels?  Policy: “aminoglycosides and vancomycin - trough drawn immediately before the fourth dose”.  Don’t assume it’s going to be done.  Write the order & be specific, especially with timing(s).  For pts with rapid clearance, trough prior to 4th dose, peak after 4th dose may be ok.  For pts with slow clearances, consider drawing levels around 3rd dose.  For pts with very slow clearances and/or changing renal function, consider drawing trough before 2nd dose.
  • 37. Please be careful….calculators don’t think, they only give answers….  Units – make sure you’re entering correctly? - kg or lbs? - cm or inches? - non-US calculators may use different units for SCr (umol/L)  Get someone else to independently verify your answers.  Use convenient dosing intervals, i.e., Every 6, 8, 12, 24, 48, 72 hour dosing intervals.
  • 38.
  • 39. Be judicious, but give adequate dose.. With reasonable dosing and appropriate monitoring, the consequences of an untreated infection are usually worse the toxicities of most antibiotics, even aminoglycosides and vancomycin…. Aminoglycoside toxicity does not usually occur before 5 days. Vancomycin, usually longer…..
  • 40. Monitoring/Vancomycin  Trough immediately prior (30 minutes) to 4th dose or earlier if patient has impaired renal function.  Monitor vancomycin trough and serum creatinine levels at least weekly if renal function stable and 2-3 times weekly for patients with unstable renal function.
  • 41. Toxicity/Vancomycin  Nephrotoxicity most common. - Usually reversible, especially if caught early.
  • 42. Monitoring/Aminoglycosides  Conventional dosing: IV: trough prior (30 minutes) to 4th dose, peak (30 minutes) after infusion of the 4th dose. IM: trough 30 minutes before injection, peak 1 hour after IM injection.  Extended interval dosing: random aminoglycoside level 6 to 14 hours after the end on infusion.  Monitor antibiotic and serum creatinine levels at least weekly if renal function stable and 2-3 times weekly for patients with unstable renal function.
  • 43. Toxicity/Aminoglycosides  Aminoglycoside toxicity usually does not occur within the first 5 days of therapy…. - be careful… usually does not always equate to never….  Nephrotoxicity most common: - usually acute tubular necrosis. - if caught early, usually reversible.  Ototoxicity less common: - Auditory (Higher frequencies. May progress to lower frequencies). - Vestiublar (loss of balance, headache, nausea, nystagmus, etc). - Rarely reversible.
  • 44. When you get labs/levels back…. Figure out where you are…. Before jumping to conclusions..  Doses given?  Doses given on time?  Sample (peak/trough) drawn appropriately?  If something looks amiss, it probably is..  Multiple places for errors to occur.
  • 45. Screen vanc/AG orders for over/under-dosage…..  Assume dose ordered is inappropriate.  Obtain information the same as if pharmacy was consulted for dosing, even if we’re not dosing.  Make sure dose is appropriate for indication for which it is prescribed.  Notify appropriate staff (physician, nursing, etc.) if dose is outside of reasonable prospective levels.  Insure appropriate monitoring labs are ordered.