Exam 2 lecture 4 pt 2

Question 1

What bacteria are aminoglycosides primarily active against

Answer 1

Primarily active against aerobic bacteria

Question 2

What organisms should we be looking at for Aminoglycosides

Answer 2

Staph Aureus
Pseudomonas aeroginosa
enterococcus
MDR gram negatives

Question 3

What is special about aminoglycosides

Answer 3

Group antibiotics that are dosed individually for each patient and require serum concentration monitoring

Question 4

What are the most commonly used aminoglycosides

Answer 4

Gentamycin
Tobramycin
Amikacin

Question 5

Are aminoglycosides polar or non polar? How does this affect their MOA

Answer 5

Are very polar

Polycationic
Water soluble
Incapable of crosiing lipid membrane

Question 6

What bond holds aminoglycosides together?

Answer 6

glycosidic bond (oxygen between rings)

Question 7

MOA of aminoglycosides? Bacteiostatic/cidal? why?Time/concentration?

Answer 7

Are one of the only protein synthesis inhibitors that are cidal in nature. This is bc it irreversibly bind 30S subunit.

Concentration dependent

Question 8

Mechanism of resistance of aminoglycoside

Answer 8

1. Synthesis of aminoglycoside modifying enzyme (most common)
   - Plasmid mediated; enzyme modifies structure of aminoglycoside leading to poor uptake and ribosomal binding
2. Alteration in ribosomal binding sites
3. Alteration in aminoglycoside uptake

Question 9

Cross resistance of Aminoglycoside

Answer 9

Tobramycin and gentamycin have cross resistance

Question 10

What drug do we primarily see alteration in ribosomal binding? Why?

Answer 10

Streptomycin only binds to a single site.

Genta, tobra, amika bind to multiple sites so they can still exert activity by binding other sites

Question 11

spectrum of activity of aminoglycosides (what type of bacteria is it primarily active against?)

Answer 11

Primarily aerobic bacteria

For gram positives we ALWAYS use them in combinations

For gram negative we often use them in combination

Question 12

What dose should aminoglycosides be used in in gram positive vs gram negative agents

Answer 12

Gram positive- low dose
Gram negative- high dose

Question 13

What gram positive aerobes is aminoglycoside active against? What is the target organism?

Answer 13

Viridians streptococci (gent)
Enterococcus spp (gent or strepto)
most S aureus* (target organism)

Question 14

What are gram negative aerobes aminoglycosides are used in? What is the target organism What drugs are used for gram negative aerobes

Answer 14

Gentamamycin, Tobramycin, amikacin and plazomycin

E coli, K pneumonia, proteus spp, Acinetobacter (not P), citrobacter, enterobacter spp, morganella, salmonella, providencia, serratia, shigella

Pseudomonas aeruginosa* (target organism)

PPPEEACKSSS

Question 15

Do we use gent for monotherapy for MSSA or MRSA

Answer 15

No, always in combination

Question 16

Which Aminoglycosides are the most effective for gram negative aerobes/ cover more strains

Answer 16

Amikacin and plazomycin

Question 17

Does plazomycin have activity against acinetobacter?

Answer 17

no

Question 18

Do aminoglycosides act against anaerobes?

Answer 18

Inactive against anaerobes

Question 19

What is post antibiotic effect (PAE)? Do aminoglycosides have it?

Answer 19

PAE is suppression of bacterial growth after serum concentrations have fallen below MIC

Question 20

What are aminoglycosides synergistic with? What does this synergism target?

Answer 20

Observed with AGs and cell wall active agents against enterococcus spp, staphylococcus spp, ciridians strep and gram negatives

Question 21

WHat are soe cell wall active agents

Answer 21

B lactams and vancomycin

Question 22

Can aminoglycosides be used as monotherapy for tx of infections due to gram positive aerobes

Answer 22

No, they should always ben used with cell wall active antibiotics in tx of infections to gram positive aerobes

Question 23

Are aminoglycosides polar or non polar? How does this affect PK characteristics?

Answer 23

Highly polar

SO water soluble they are eliminated unchanged

Question 24

Why do we individualize dosing of aminoglycosides

Answer 24

Interpatient variability exists in Vd and clearence

Question 25

Are aminoglycosides concentration or time dependent? Cidal/static?

Answer 25

Concentration dependent bactericidal activity

Question 26

What does the absorption look like for aminoglycosides? Preferred ROA?

Answer 26

Poorly absorbed from GI tract, must use parenteral administration IM injection Intermittent IV infusion preferred (G,t,a,p)

Question 27

What are oral aminoglycosides

Answer 27

Oral neomycin and oral paramamycin

Question 28

When not to use IM injection for aminoglycosides

Answer 28

Hypotensive pts

Question 29

desscribe distribution of aminoglycosides (CSF, lungs, adipose) IBW or ADW for dosing?

Answer 29

Distribute poorly in CSF, lungs and adipose tissue Use IBW (or ADW in obese patients) for dosing

Question 30

What are factors we must take into account when calculating dose for aminoglycoside

Answer 30

Volume status must be taken into account to calculate appropriate dose

Question 31

How are aminoglycosides eliminated? What does elimination half life depend on?

Answer 31

85-95% eliminated in kidneys Elimination half life depends on renal function

Question 32

What is necessary monitoring required in ALL patients receiving aminoglcosides

Answer 32

Serum concentration monitoring is necessary in ALL pts

Question 33

Why do we monitor serum concentration for aminoglycoside

Answer 33

IT IS IMPERATIVE to achieve therapeutic concentrations quickly to decrease mortality

Question 34

When dosing Aminoglycosides, What is standard dosing based on? What does gram positive dosing come out as? What does gram negative dosing come out as?

Answer 34

Lading dose and maintenance dose based on Vd, IBW or ADW and desired peak Gram positive synergy- 1mg/kg gent gram negative- LD- 2-2.5 g/kg/dose gent, tobra MD- 1.5-2 mg/kg/dose gent, tobra

Question 35

What are the target peaks/troughs of gent and tobra for mod infection (UTI), mod-severe (SSTI, bacteremia), Severe (pneumonia, burn, life threat) Peak/trough for gram positive synergy (EXAM)

Answer 35

mod infection (UTI)- Peak= 4-6 mcg/ml, trough= 0.5-1.5 mcg/ml Mod-severe (SSTI, bacteremia)- peak= 6-8, trough 1-1.5 Severe (pneumonia, burn, life threat)- Peak=8-10, trough=<2 Gram positive synergy- peak= 3-5 mcg/ml, Trough= 1 mcg/ml

Question 36

How to dose aminoglycosides once daily? What type of patients can we use this in?

Answer 36

Gent/tobra= 7 mg/kg. Use IBW or ADW Only in gram negative bacteria and patients with normal Crcl (>40-50)

Question 37

target serum concentrations for QD dosing? (peak/trough) EXAM

Answer 37

Gent, tobra- Peak= 13-20, Trough <0.5 Amikacin- peak= 40-50, trough <8

Question 38

clinical uses of aminoglycosides? Which aminoglycosides are used for gram negative aerobes? Which are used with gram positive aerobes

Answer 38

Used in combination with cell modifying agents to treat gram negative aerobes and gram positive aerobes Gent, tobra, amikacin used in gram negative aerobes. including pseuomonas aerioginosa in combination with B lactams Gentamicin and streptomicin used for synergy with cell wall wall active agent for gram positive aerobes Streptomicin used for TB

Question 39

What is plazomycin used for?

Answer 39

Complicated UTI due to MDR gram negative aerobes

Question 40

What are gram positive aerobes that we use gentamicin/streptomycin for?

Answer 40

Endocarditis due to enterococci Viridians strep Staph aureua (including NRSA)

Question 41

Adverse effects of aminoglycosides

Answer 41

Nephrotoxicity Ototoxicity

Question 42

Risk factors for aminoglycosides nephrotoxiciy? ototoxicity?

Answer 42

Prolonged high troughs, long duration of therapy (>2 wks), underlying renal dysfunction, elderly, hypovolemia Same risk factors

Question 43

Which of the following antibiotics does NOT have activity against pseudomonas aeruginosa. Cefepime, Ciprofloxacin, tobramycin, piperacillin, Ceftriaxone

Answer 43

Ceftriaxone

Question 44

Which antibiotic does NOT cause nephrotoxicity Gentamicin, Televancin, Vancomycin, Azithromycin, Nafcillin

Answer 44

Azithro