Day2: Dr. Jayakumar Flashcards
What are important things to know about gram positive organisms
They have a large (50-90%) peptidoglycan component of cell wall
Maintains crystal violet and is a purple/blue stain
What is important to know about gram negative organisms?
Small (10%) component of peptidoglycan in cell wall
Alcohol decolonizes thus maintains last dye of safranin to stain red/pink
What are example of gram positive bacteria?
Staphylococcus app
S. Aureus
S. Epidermidis
Streptococcus app
ENTERococcus spp
What are examples of gram negative bacteria?
Escherichia coli
Klebsiella
ENTERObactor
Serratia
Proteus
Pseudomonas
Acinetobacter
What are Vancomycin pharmacokinetics?
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)
What can you treat with vancomycin?
Gram Positive only!
MRSA is a big one that is used
Has ZERO activity against gram negatives
Gentamicin and Tobramycin pharmacokinetics
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
What is the spectrum of activity for aminoglycosides?
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
What is the MIC?
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
What is Time-Dependent Killing?
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
What is concentration-Dependent killing?
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
What is the AUC/MIC goal for vancomycin?
Higher doses and troughs are needed to get AUC/MIC greater than or equal to 400
What is the amt of a loading dose, also when would you use it?
What is the initial Maintenance dose?
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
What is the dosing weight for Vanco?
What is the MAX single dose of vanco?
What do you round vanco to?
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
What is the Goal serum trough concentration of non complicated infections?
Examples: UTI, Skin/skin structure
10-15 is optimal
What is the goal serum trough concentration for more complex infections for vanco? Also how do you remember which ones are complex?
E - endocarditis (heart valve) M- Meningitis O- Osteomyelitis P- Pneumonia S- Sepsis (systemic)
Goal is a trough of 15-20 mcg/mL
When are you supposed to measure Trough levels?
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)
What are some reasons why a trough might be too low?
Dose is too low
Not frequent enough dosing
Drug not at steady state
Trough drawn too late
What would be the cause of a trough being too high?
Dose is too high
Too frequent of dosing
Trough was drawn when drug was infusing or shortly after infused
How do you adjust the dosing regimes of vanco based on the vanco troughs?
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
What are the two main types of side effects that need to be considered for Vanco safety?
Nephrotoxicity
Ototoxicity
What causes the nephrotoxicity that comes from vanco?
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
What causes ototoxicity when using vanco?
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
What is Redmans syndrome?
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
What are the summary of guidelines that should be known for vanco? IDSA guidelines
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
What are the two types of dosing for Aminoglycosides?
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
When do you get a peak (Cmax) when using traditional dosing of an Aminoglycosides
It happens 1 hour after infusion STARTS
Typically give the infusion for 30 min or 1 hr
What are the goal peak concentrations and goal trough concentrations for Aminoglycosides
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
What is the dosing and dosing weight for Traditional gentamicin in gram positive infections?
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
What is the rationale for extended interval?
What’s used for gram negative bacteria
- Aminoglycosides are concentration-dependent killers
They have improved efficacy due to higher doses
Cmax (peak) / MIC > 10 has best efficacy - Prolonged post-antibiotic effects
Continued bacterial killing even tho serum inhibitory concentrations have follows below minimum inhibitory concentration - Reduced emergence of bacterial resistance
- Decreased uptake into sites of toxicity (kidney and inner ear)
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?
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
Aminoglycosides safety considering nephrotoxicity. What’s important to know?
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)
Aminoglycosides safety considering ototoxicity. What’s important to know?
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
What is the summery of Extended interval dosing for Aminoglycosides in terms of bacterial targets, Drug dosing and drug frequency?
Bacterial targets: Gram negative
Drug dosing: 7mg/kg/dose (use TBW or AdjBW)
Drug frequency: Q24h or per nomogram
What is the summery of synergy dosing for Aminoglycosides in terms of bacterial targets, Drug dosing and drug frequency?
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
