AMGs - SOA

Question 1

List the aminoglycosides (AMGs):

Answer 1

• gentamicin
• tobramycin
• amikacin
• streptomycin
• plazomicin (new)

Question 2

What is the mechanism of action of the AMGs?

Answer 2

• AMGs inhibit protein synthesis by irreversibly binding to 30S ribosomal subunits.

Disruption in initiation of protein synthesis

Question 3

What kind of activity to AMGs display?

Answer 3

• rapid
• concentration dependent
• bactericidal

Question 4

What are the mechanisms of resistance to the AMGs?

gentamicin, tobramycin, amikacin, streptomycin, plazomicin

Answer 4

• altered AMG uptake
• synthesis of AMG-modifying enzymes

Streptomycin only binds to a single site at the 30S ribosomal subunit, so it is also susceptible to resistance via alteration in ribosomal binding site.

Question 5

Which PK parameter correlates best with clinical efficacy for the AMGs?

Answer 5

peak:MIC

Peak:MIC ratio of 10 to 1 is optimal

Question 6

What is the general SOA of the AMGs?

Answer 6

• some activity against GP aerobes
• very active against GN aerobes

Question 7

How are AMGs used for GP aerobes?

Answer 7

They are NEVER used alone.
They are always used in LOW DOSES with cell-wall active agents to provide synergy.

Question 8

How are AMGs used in GN aerobes?

Answer 8

AMGs are often used with cell-wall active agents to provide synergy.
HIGH DOSES of AMGs are used in GN aerobes.

Question 9

What target organisms do AMGs cover?

Answer 9

• MSSA
• MRSA
• pseudomonas aeruginosa (A,P>T>G)

• strepotmycin is not active against pseudomonas

Question 10

Describe the pharmacokinetic characteristics of the AMGs:

Answer 10

• AMGs are highly polar cations –> lack of absorption after oral administration
• volume of distribution and clearance vary from patient to patient –> dosing has to be patient-specific

Question 11

How are AMGs distributed?

Answer 11

• AMGs are distributed primarily in the extracellular fluid compartment.
• Distribute poorly into CSF and adipose

Question 12

Which weight should be used for AMG dosing?

Answer 12

ideal body weight

Adjusted body weight for obese patients

Question 13

How are the AMGs eliminated?

Answer 13

• AMGs are primarily eliminated unchanged by the kidneys via glomerular filtration
• decreases in renal function prolong the half-life

Question 14

What patient factors should be considered when dosing AMGs?

Answer 14

• gender
• renal function
• age
• weight
• volume status
• infection
• severity of infection

GRAWVIS

Question 15

What are the target peak and trough concentrations for traditional dosing of gentamicin and tobramycin in gram-negative infections?

mod, mod-sev, sev

Answer 15

• Moderate: peak of 4-6, trough of 0.5-1.5
• Mod-severe: peak of 6-8, trough of 1-1.5
• severe: peak of 8-10, trough of <2

units = ug/mL

She always targets 1 for the trough no matter what.

Question 16

What is the target peak and trough concentration for gentamicin and tobramycin for once daily dosing in the treatment of gram-negative infections?

Answer 16

• Peak of 13-20 ug/mL
• trough of < 0.5 ug/mL

Question 17

How are AMGs used clinically?

Answer 17

They are never used alone (except for plazomicin).

Used with cell wall synthesis inhibitors like B-lactams or vanc

Question 18

What are the adverse effects of the AMGs?

Answer 18

• Nephrotoxicity - reversible
• ototoxicity - irreversible

Question 19

What are the risk factors for developing nephrotoxicity and/or ototoxicity from AMGs?

Answer 19

• prolonged high trough concentrations
• therapy longer than 2 weeks
• underlying renal insufficiency
• older age
• hypovolemia
• use of concomitant nephrotoxins