Part 2 – Aminoglycoside & Vancomycin dosing

Pharmacy to dose: - a dose - a frequency - monitoring/labs

Basic patient information

NameGenderAgeHeight Weight

the patient – information for dosing…

Other essential informationfor 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, clearProtein negativeNitrite negativeWBC 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 SLevofloxacin SNitrofurantoin* SPenicillin S Tetracycline RVancomycin 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 calculatorGlobal 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 4-6Cystitis 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 4-6Soft 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 facilitiesdon’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.