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Aminoglycosides
N/A
60
Microbiology
Professional
06/24/2012

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Cards

Term
What are the commonly used AG in clinical practice?
Definition
1. Gentamicin
2. Tobramicin
3. Amikacin
4. Streptomicin
5. Neomycin (topically used)
Term
What is the MOA of AG?
Definition
1. Inhibit protein synthesis by irreversibly binding to bacterial ribosomes 30S, interfering with translational accuracy of mRNA
2. Other mechanisms include cell wall activity via ionic interactions with the cell wall
3. They have been shown to disrupt and leave holes in the cell wall causing "bacterial bleeding"
4. In most cases, AG are CIDAL
Term
How much toxicity from the AG are we going to accept?
Definition
The amount of toxicity we are willing to accept depends on the severity of the infection
Term
Is renal dysfunction caused by AG reversible?
Definition
For the most part, renal dysfunction is reversible
Term
AG calculations are based on what compartment model?
Definition
Calculations are usually based on a 1-compartment model
Term
AG display what kind of compartment kinetics?
Definition
AG display 2-3 compartment kinetics so when monitoring levels, there is a need to avoid 1st and 3rd distribution phases unless using QD dosing
Term
With AG, which has higher concentrations? Tissue or serum?
Definition
Concentrations in the tissue are lower that in the serum
Term
Can AG penetrate the CSF?
Definition
CSF penetration is poor
Term
AG display what kind of killing?
Definition
AG and QN display concentration dependent killing, so the higher the concentration, the better the kill
Term
Does AG have post-ab effect?
Definition
Yes, but the duration of the post-ab effect is organism dependent and dose dependent
Term
How long is the half-life of AG?
Definition
T1/2 = 2 hrs in patients with normal kidney function

T1/2 = 0.693/Kd
Term
What is the Vd of AG?
Definition
Vd = 0.25-0.4 L/kg based on IBW (use ABW if obese)
Term
Dose AG distribute into adipose tissues?
Definition
No, the Vd is similar to ECF and distributes poorly into adipose tissue
Term
How do you calculate Vd in obese patients?
Definition
Vd = 0.25L/kg

ABW = IBW + 0.4(Actual - IBW)
Term
What is the relationship between AG and CrCl?
Definition
AG clearance is proportional to GFR (CrCl)
Term
Is AG dialyzable?
Definition
Yes, can be removed by hemodialysis, peritoneal dialysis & continuous hemofiltration (membranes determine quantity removed per unit of time on dialysis)
Term
If greater than 65 yo, which SCr do you use?
Definition
Minimum SCr = 1
Term
How do you calculate the elimination rate constant?
Definition
Kd (hr-1) = CL (L/hr)/Vd (L)
Term
How do you calculate a LD for AG?
Definition
LD = (desired AG serum conc.) CPss * Vd
Term
Why do we base dosing off of lean body tissue (IBW)?
Definition
Because AG are based off a 1 compartment model (water) and most of the water are in muscle
Term
Can AG be used in combo or as monotherapy?
Definition
Usually used as part of a combination that is synergistic and in rare cases, can be used alone as monotherapy like in uncomplicated UTI
Term
What is the spectrum of activity of AG?
Definition
1. Gram (-) organisms:
Enterobacteriaceae
Pseudomonas aeruginosa
Serratia
M. tuberculosis
Mycobacterium Avium (MAC)
SPACE
2. Gram (+) organisms:
Enterococci
Streptococci
Staphylococci
Listeria
(do not cover strict anaerobes without facilitation)
Term
Why can AG be used as monotherapy in treatment of uncomplicated UTI?
Definition
Bc AG are highly concentrated in the kidneys and so are highly concentrated in the urine (drug can be concentrated ip to 50 times in the urine -- AG + water)
Term
For gram (+) organisms, which of the AG are more potent?
Definition
Gentamicin!
Term
For gram (-) organisms, which of the AG are more potent?
Definition
Tobramycin!
Term
Which AG is MOST potent in general?
Definition
Amikacin!
Term
When using AG, which are the toxicity concerns we have?
Definition
1. Nephrotoxicity (associated with trough levels)
2. Ototoxicity (associated with peak levels)
3. Neuromuscular blockage
Term
Is nephrotoxicity reversible? And when is the onset of nephrotoxicity induced by AG?
Definition
Usually reversible, occurs 5-7 days after therapy
Term
Why does nephrotoxicity occur?
Definition
Bc AG have high affinity for proximmal tubule cells and may cause ATN and proximal tubular injury and cell necrosis
Term
What are the risk factors for ATN?
Definition
1. Long duration of treatment
2. Trough levels > 2mg/L and time
3. Repeated courses within a few months
4. Elderly >/= 65 yo
5. Malnutrition
6. Volume depletion
7. Pre-existing liver/renal disease
8. Potassium/magnesium depletion
9. Other nephrotoxic drugs
Term
Is ototoxicity reversible?
Definition
Usually irreversible
Term
What are s/sx of ototoxicity?
Definition
Tinnitus or feeling of fullness in the ears (don't complain of hearing loss until significant damage is done)
- Vestibular: N/V, cold sweats, nystagmus, vertigo
- Watch w/ concommitant ototoxic agents (Loop D, erythromycin)
- Watch w/ close-proximity ototoxic agents Platinum agents, Vinca's
Term
How does AG affect neuromuscular blockage?
Definition
AG prolongs neuromuscular blockage
Term
What are the risk factors for AG-induced neuromuscular blockage?
Definition
1. Concurrent neuromuscular blockers
2. CCB
3. Electrolyte abnormalities
4. Myasthenia Gravis
Term
What are the clinical uses of AG?
Definition
1. Gram (-) nosocomial pneumonia
2. Bacteremia
3. Pyelonephritis
4. Urosepsis
5. Sepsis
6. Polymicrobial infections
7. Febrile neutropenia
Term
How can we cover Enterococcus with AG?
Definition
In combo with beta lactams (PCN or Amp) - gent preferred (Gram (+) = Gent; Gram (-) = Tobra)
Term
What can we use for Enterococcus resistance?
Definition
1. Vancomycin (Vancocin)
2. Linezolid (Zyvox)
Term
How do you treat coagulase (-) staph endocarditis?
Definition
Combo with vanco and rifampin
Term
How do you treat staph. aureus endocarditis?
Definition
Combo with antistaph PCN with AG
Term
What is the usual dosing intervals for AG?
Definition
Usually 8-12 hrs, sometimes 24 with poor renal function
Term
What is the dosing for urinary, tissue, lungs/blood
Definition
1. Urinary: 1mg/kg (5) synergistic dose
2. Tissue: 1.5mg/kg (6) moderate infection
3. Lung/blood: 2mg/kg (7) moderate/severe infections
Term
When are drug levels usually obtained?
Definition
- Usually obtained after the 3rd dose
- Peak: obtain 30 min after a 30 min infusion or 15 min after 60 min infusion
- Trough: Just prior to the 4th dose
Term
What are the peak targets for gent/tobra and amikacin?
Definition
1. Gent/Tobra peak
UTI: 3-5 mcg/mL
Skin & soft tissue infections: 5-7mcg/mL
Pneumonia & sepsis: 7-10 mcg/mL
2. Amikacin
UTI: 20 +/- 5 mcg/mL or 25
Skin & soft tissue infection: 25 +/- 5 mcg/mL or 30
Pneumonia & sepsis: 30 +/- 5 mcg/mL or 35
Term
What are the trough levels we want?
Definition
1. Gent/Tobra: <2 mcg/mL
2. Amikacin: <10 mcg/mL
Term
What is the maximum peak for Gent?
Definition
<10 mcg/mL
Term
Why do we use High dose, once daily dosing?
Definition
1. Optimize PK/PD properties
2. High dose therapy is less nephrotoxic
3. Resistance
Term
For once daily dosing, what is the peak for Gent/Tobra and Amikacin?
Definition
1. Gent/Tobra = 20 mcg/mL
2. Amikacin = 60 mcg/mL
Term
What is the once daily dose for Gent/Tobra and Amikacin?
Definition
1. Gent/Tobra = 7 mg/kg
2. Amikacin = 15 mg/kg
Term
What is the dosing interval for once daily AG?
Definition
CrCl >60: Q24 hrs
CrCl 40-59: Q36 hrs
CrCl 20-39: Q48 hrs
CrCl < 20: monitor serial levels
Term
How do you monitor once daily AG levels?
Definition
Random conc after the 1st does between 6-12 (14) hr after the start of the infusion
Term
How long do we infuse once daily AG?
Definition
Infusion is usually over 60 min
Term
When is once daily dosing not recommended for?
Definition
1. Enterococcal endocarditis
2. Pregnancy
3. Select pediatric populations
4. Cystic fibrosis
5. Burns (Vd is unpredictable)
6. Renal failure (CrCl<10mL/min)
Term
High level Gent resistant enterococcus may be sensitive to what other AG?
Definition
Streptomycin
Term
Synergy doses do not require levels...what does this mean??
Definition
Everyone gets 1mg/kg, and no body gets level bc you are not using it for peak/trough, you are just using it for synergy dose
Term
How do you treat abscess?
Definition
You need to drain abscess bc AG can't perfuse in there (can only penetrate tissues)
Term
When should drug levels be obtained after hemodialysis?
Definition
2 hrs after hemodialysis
Term
Is monitoring necessary for patients with normal renal function who will be on therapy for <5 days?
Definition
Not really
Term
What do you do for patients with ascites/edema?
Definition
For ever 1 kg of weight gained, you need to increase Vd by 1 L (look at I/O)
Term
Is it ok to add PCN along with AG in the same IV bag?
Definition
No! You can NEVER let antipseudomonal PCN or ANY PCN come into contact with AG
bc can inactivate AG (Gent/Tobra are more problematic than Amikacin)
Term
When on AG therapy, which lab value do you need to monitor daily?
Definition
SCr
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