Day2: Dr. Jayakumar

Question 1

What are important things to know about gram positive organisms

Answer 1

They have a large (50-90%) peptidoglycan component of cell wall

Maintains crystal violet and is a purple/blue stain

Question 2

What is important to know about gram negative organisms?

Answer 2

Small (10%) component of peptidoglycan in cell wall

Alcohol decolonizes thus maintains last dye of safranin to stain red/pink

Question 3

What are example of gram positive bacteria?

Answer 3

Staphylococcus app
S. Aureus
S. Epidermidis

Streptococcus app

ENTERococcus spp

Question 4

What are examples of gram negative bacteria?

Answer 4

Escherichia coli

Klebsiella

ENTERObactor

Serratia

Proteus

Pseudomonas

Acinetobacter

Question 5

What are Vancomycin pharmacokinetics?

Answer 5

Absorption: Poor oral absorption

Distribution: Widely into most body tissue except CSF
Vd = 0.7 L/kg for non-obese patients
Vd= 0.8 L/kg for obese patients

Exertion: 40-100% excreted unchanged in urine

Elimination: t1/2 4-6 hours in patients with normal renal function (CrCl > 50 mL/min)

Question 6

What can you treat with vancomycin?

Answer 6

Gram Positive only!

MRSA is a big one that is used

Has ZERO activity against gram negatives

Question 7

Gentamicin and Tobramycin pharmacokinetics

Answer 7

Absorption: Less than 0.2% oral, but rapid IV and IM

Distribution: Protein binding 0-30%
Vd: 0.25 L/kg for adults. (The drug is very hydrophilic which means that if you are obese you don’t need to adjust dose since it doesn’t go into fat)

Excretion: 70-100% excreted in the urine
T1/2: 4-6 hours with normal renal function

Question 8

What is the spectrum of activity for aminoglycosides?

Answer 8

Excellent activity against gram negative organisms

gentamicin/tobramycin can be used against some gram positive when used in combo with a cell wall active agent (vanco/beta-lactams) (this is because aminoglycosides work within the cell at RNA at 30S subunit, the cell wall agent breaks open the wall so these could go in and work) THIS IS SYNERGY

Question 9

What is the MIC?

Answer 9

It’s the minimum inhibitory concentration

You do it by putting a known quantity of bacteria in a tube with zero antibiotic. Then you make other tubes with the same amt of bacteria but double the amt of Antibitoic in those tubes and look to see when he bacteria dies

Question 10

What is Time-Dependent Killing?

Answer 10

It’s when you need to keep the drug concentration above the MIC over a period of time and the Cmax or peak doesn’t matter as much.

Beta-lactams are big with this

Question 11

What is concentration-Dependent killing?

Answer 11

This is when you need to get a high amt of drug into the body but the amount its there does not matter as much. You just need a high concentration or get Cmax (peak to the correct amt)

Aminoglycosides and Daptomycin are the ones that do this

Only way we can change Cmax= Dose/ Vd. We cant change a persons Vd so we can only increase dose in order to increase Cmax

Question 12

What is the AUC/MIC goal for vancomycin?

Answer 12

Higher doses and troughs are needed to get AUC/MIC greater than or equal to 400

Question 13

What is the amt of a loading dose, also when would you use it?

What is the initial Maintenance dose?

Answer 13

Loading dose: 25 mg/kg
It’s only used for seriously ill patients and it is optional

Initial Maintenance dose: 15 mg/kg give every 8-12 hours

***you alter these doses based off of TROUGH concentrations that are optioned

Question 14

What is the dosing weight for Vanco?

What is the MAX single dose of vanco?

What do you round vanco to?

Answer 14

You use the Total body weight (TBW)

2000mg and should avoid 4000mg a day (will get bad side effects)

Round to the nearest 250 mg

Question 15

What is the Goal serum trough concentration of non complicated infections?

Answer 15

Examples: UTI, Skin/skin structure

10-15 is optimal

Question 16

What is the goal serum trough concentration for more complex infections for vanco? Also how do you remember which ones are complex?

Answer 16

E - endocarditis (heart valve)
M- Meningitis 
O- Osteomyelitis 
P- Pneumonia
S- Sepsis (systemic)

Goal is a trough of 15-20 mcg/mL

Question 17

When are you supposed to measure Trough levels?

Answer 17

It must be done WITHIN 60 minutes prior to the next dose!

Also it must be checked prior to the 4th dose (this will ensure that you have enough time in order to reach steady state)

Question 18

What are some reasons why a trough might be too low?

Answer 18

Dose is too low

Not frequent enough dosing

Drug not at steady state

Trough drawn too late

Question 19

What would be the cause of a trough being too high?

Answer 19

Dose is too high

Too frequent of dosing

Trough was drawn when drug was infusing or shortly after infused

Question 20

How do you adjust the dosing regimes of vanco based on the vanco troughs?

Answer 20

First make sure that the trough was true

Use the TDD (total daily dose) / Measured mean trough) = X (new TDD trying to get ) / Mean goal trough

How to determine mean goal trough

For uncomplicated the goal is 10-15 meaning the mean goal is 12.5

For complex goal is 15-20 so mean goal is 17.5

Then cross multi and don’t forget to convert it into a reasonable dosing regimen

Question 21

What are the two main types of side effects that need to be considered for Vanco safety?

Answer 21

Nephrotoxicity

Ototoxicity

Question 22

What causes the nephrotoxicity that comes from vanco?

Answer 22

Associated with prolonged trough concentrations > 20 mcg/mL

Defined as a increase of serum creatinine of 0.5 mg/dL or > 50% increase from baseline

**Happens in pats who have poor perfusion to the kidneys or receiving other nephrotoxic medications

Question 23

What causes ototoxicity when using vanco?

Answer 23

Less common than nephro

Associated with peaks > 80 mg/L

Will get tinnitus, dizzy, and lose high frequency hearing

Dmg will be permanent if vanco dose is not adjusted

Question 24

What is Redmans syndrome?

Answer 24

It happens when you infuse vanco to quickly. You should infuse no faster than 1g / hr

Will usually happen within the first 15-30 minutes and you can stop it by infusing the drug over a longer period of time

**its a histamine release, which causes hypotension and rash on face, trunk, neck and upper extremities

Question 25

What are the summary of guidelines that should be known for vanco? IDSA guidelines

Answer 25

Loading dose ( Optional): 25 mg/kg Maintenance dose: 15 mg/kg Weight utilized: TBW Drug frequency: Q8h or Q12h (CrCl > 50 mL/min), less frequent dosing if pt CrCl < 50 mL/min Monitor Trough: 10-15 mcg/ mL for uncomplicated 15-20 mcg/mL for complicated (EMOPS) * ***MAX single dose is 2g * *** Caution with using over 4g per day

Question 26

What are the two types of dosing for Aminoglycosides?

Answer 26

Traditional: used primarily only for Gram positive and used be used with another antibiotic such as beta-lactam or vanco. (Also known as synergy dosing) Extended Interval dosing: this is used for gram negative organisms

Question 27

When do you get a peak (Cmax) when using traditional dosing of an Aminoglycosides

Answer 27

It happens 1 hour after infusion STARTS Typically give the infusion for 30 min or 1 hr

Question 28

What are the goal peak concentrations and goal trough concentrations for Aminoglycosides

Answer 28

Goal peak (only used for traditional dosing and gram positive infections) 3-5 mcg/ mL Goal trough concentration (for both Gram negative and positive bacteria) < 2.0 mcg / mL

Question 29

What is the dosing and dosing weight for Traditional gentamicin in gram positive infections?

Answer 29

Dosing: 1 mg/kg (TBW or AbjBW) IV q8h Dosing weight: Use Total body weight if non-obese Use Adjusted body weight if pt is obese If CrCl < 50 ml/min use q12h or once daily * **round to the nearest 20 mg * **this is never a mono therapy for gram positive and must be used with cell active antibiotic

Question 30

What is the rationale for extended interval?

Answer 30

What’s used for gram negative bacteria 1. Aminoglycosides are concentration-dependent killers They have improved efficacy due to higher doses Cmax (peak) / MIC > 10 has best efficacy 2. Prolonged post-antibiotic effects Continued bacterial killing even tho serum inhibitory concentrations have follows below minimum inhibitory concentration 3. Reduced emergence of bacterial resistance 4. Decreased uptake into sites of toxicity (kidney and inner ear)

Question 31

What is Aminoglycosides extended dosing? Like when is it used, how often do you dose, what’s the frequency based off, how do you determine how to use Hartford nomogram?

Answer 31

Only used for Gram negative infections Sometimes called once daily dosing but you can use q24h, q36h, q48h The dosing frequency is based on Hartford nomogram ***you pick this by choosing a random level between 6 and 14 hours after the start of infusion used BASE DOSE OFF OF 7 mg/kg with TBW or AbjBW

Question 32

Aminoglycosides safety considering nephrotoxicity. What’s important to know?

Answer 32

Defined as increase of serum creatinine of 0.5 mg/dL or > 50% increase from baseline The drug accumulates in tubular cells of kidney resulting in acute tubular necrosis and subsequent, decreased GFR **Genta>_ Tobramycin > amikacin It’s associated with prolonged trough concentrations > 2-3 mcg/mL (usually dosed occur before 3-5 days of therapy)

Question 33

Aminoglycosides safety considering ototoxicity. What’s important to know?

Answer 33

Aminoglycosides accumulate in the lymph of the inner ear and may cause dmg to cochlear (the little hairs is in the ear can fall off and cause perm dmg) (3-14%) or vestibular (sensory cells and can effect balance and make people get dizzy) **likely related to AUC (overall exposure) and trough ***first sign is usually tinnitus

Question 34

What is the summery of Extended interval dosing for Aminoglycosides in terms of bacterial targets, Drug dosing and drug frequency?

Answer 34

Bacterial targets: Gram negative Drug dosing: 7mg/kg/dose (use TBW or AdjBW) Drug frequency: Q24h or per nomogram

Question 35

What is the summery of synergy dosing for Aminoglycosides in terms of bacterial targets, Drug dosing and drug frequency?

Answer 35

Bacterial targets: gram positive Drug dosing (gentamicin/tobramycin): 1mg/kg/dose (based off ABW or AdjBW) Drug frequency: Q8h or less frequent dosing for CrCl < 50mL/min