Aminoglycosides

Question 1

Name the 3 most important AGs. Which is a 4th that is less important?

Answer 1

• Gentamycin (gent) - Tobramycin (tobr) - Amikacin (amik) Streptomycin

Question 2

Which is the most important AG?

Answer 2

Gentamycin

Question 3

What is the general class(es) of organism(s) that gentamycin targets? What are the 3 organisms in this class that it’s most effective against? (not sire if I need to be this specific)

Answer 3

Gram-negative *Can also target gram-pos if another drug allows it to get into the cell - E. coli, Klebsiella pneumoniae, Proteus

Question 4

How does the activity of tobramycin differ from gentamycin?

Answer 4

Slightly weaker gram-neg activity but more effective against pseudomonas.

Question 5

What type(s) of pathogen(s) is amikacin effective against?

Answer 5

• Nosocomial gram-negatives (except not as good as tobr for pseudomonas) - Mycobacterial (M. tuberculosis and atypical) - Other: nocardia (rare)

Question 6

What type(s) of pathogen(s) is streptomycin effective against?

Answer 6

• Gram-pos: enterococcus (but gentamycin is preferable) - Mycobacterial (M. tuberculosis, but less effective against atypical vs. amikacin)

Question 7

What type of drugs do AG’s have synergy w/?

Answer 7

Cell-wall inhibitors (likely due to enhanced AG uptake)

Question 8

What is unique about the distribution of AGs?

Answer 8

1000-fold higher conc. in urine vs. plasma (good for treating UTIs)

Question 9

Differentiate b/w “traditional” (MDD) and “extended interval” (ODA) dosing.

Answer 9

• Traditional: multiple daily doses (q8-12 hrs) - Extended interval: once daily dosing (no less)

Question 10

With conc-dependent killing, would you aim for higher or lower peak:MIC ratio?

Answer 10

Higher (make sure you understand why)

Question 11

How is the post-antibiotic effect influenced by the peak:MIC ratio?

Answer 11

Bigger peak:MIC ratio = larger dose, and therefore larger PAE w/conc-dependent killing

Question 12

Which is more likely to create resistance: infrequent large doses, or frequent smaller doses? (Why?) - Which leaves the bacterium more susceptible to killing?

Answer 12

Frequent smaller doses (bacteria more likely to survive) - 1 large dose more effective because bacteria more susceptible during drug-free time.

Question 13

Which AGs are effective against gram-neg infections?

Answer 13

• Gentamycin - Tobramycin - Amikacin

Question 14

What type of dosing is preferred when using AGs to fight gram-neg infections?

Answer 14

Extended interval (once daily) dosing

Question 15

Which AGs are effective against gram-pos infections?

Answer 15

• Gentamycin - Strepamycin

Question 16

What type of dosing is preferred when using AGs to fight gram-pos infections?

Answer 16

Traditional dosing * Counter to what has been said, but must be given in combo w/beta-lactam drug to get it into cell. Once in cell, there is synergy w/this other drug, and don’t need as high of a dose

Question 17

Which AGs are effective against mycobacterial infections?

Answer 17

• Amikacin - Streptomycin

Question 18

What type of dosing is preferred when using AGs to fight mycobacterial infections?

Answer 18

Extended interval dosing (3 times weekly!) - Amikamycin preferable

Question 19

Explain the reasons why extended-interval dosing is preferable to traditional dosing w/r/t AGs vs. gram-neg bacteria. (6)

Answer 19

• Concentration-dependent bactericidal activity - Post-antibiotic effect (PAE) - Adaptive resistance - *Minimize toxicities - Cost savings - Efficacy

Question 20

What are some factors that influence PAE? (4, not too important)

Answer 20

• Organism - Drug concentration - Duration of drug exposure - Antimicrobial combinations

Question 21

What are the 2 major toxicities related to AGs?

Answer 21

• Nephrotoxicity - Ototoxicity

Question 22

If gram-neg bacteria suspected, AGs can be used for the empiric treatment of __________, especially from a urinary source. What other conditions could they be used for?

Answer 22

Sepsis - Intraabdominal infections - Skin/soft tissue infections

Question 23

If a pt has a h/o CF, which AG would you choose and why?

Answer 23

*Tobramycin (pt is more susceptible to pseudomonas)

Question 24

If treating PNA with AGs, would you use a low, medium, or high dose?

Answer 24

High

Question 25

Recall: when using gentamycin (or sometimes streptomycin) to treat gram positive infections, you would normally combine it with ___________, or sometimes even ___________ for severe infections (e.g. enterococcal or staphylococcal).

Answer 25

• Beta-lactams (ampicillin, nafcillin) - Vancomycin (recall: lower, traditional dosing)

Question 26

What part of the kidney is affected by AG nephrotoxicity?

Answer 26

Proximal tubule (AG uptake is saturable here)

Question 27

How are AG’s administered? What are the exceptions?

Answer 27

They are all administered IV and IM (not PO)

Question 28

What are AG’s mech of action? (Cidal or static?)

Answer 28

Irreversibly bind to 30S ribosomal subunit to inhibit ptn synth (bacteriocidal).

Question 29

What are AG’s mech of resistance?

Answer 29

Synthesis of AG-modifying enzymes (often via plasmid), altered AG uptake (efflux pump of loss of porin channel), change in ribosomal binding site/target modification

Question 30

What organ eliminates AGs?

Answer 30

Kidneys (dose must be adjusted in kidney failure)