Erdman - Aminoglycosides Flashcards
Why do aminoglycosides require serum concentration monitoring and individualized dosing for each patient?
-Interpatient variability in Vd and Cl
-Narrow therapeutic window/index
-Clinical studies have demonstrated a relationship between serum concentrations and efficacy/toxicity
-Imperative to achieve therapeutic concentrations quickly
What are the aminoglycosides?
-Gentamicin
-Tobramycin
-Amikacin
Aminoglycoside mechanism of action
-Inhibits protein synthesis
-Irreversibly binds to the 30S ribosomal subunit
What is the aminoglycoside mechanisms of action?
-Synthesis of aminoglycoside-modifying enzymes
-Alterations in ribosomal binding sites
What is the aminoglycoside gram-positive spectrum of activity?
-Enterococcus (gent or strepto)
-Staph aureus (gent)
When would you use aminoglycosides in combination with cell wall inhibitors?
-In all gram-positive aerobes
-Most gram-negative aerobes
Which drug would you use for gram-positives?
Gentamicin
What is the best drug for gram-negatives?
Amikacin/plazomicin>tobramycin>gentamicin
What is the aminoglycoside gram-negative spectrum of activity?
-PPPEEACKSSS
-Pseudomonas
Why was plazomicin developed?
To have better activity against multidrug resistant bacteria
Which bacteria do aminoglycosides have synergy with cell wall active agents?
-Enterococcus spp.
-Staph spp.
-Viridans strep
-Gram-negatives
How are aminoglycosides administered?
Intermittent IV infusion
Are aminoglycosides distributed to the CSF?
Poorly distributed to the CSF, lungs and adipose tissue
What must be taken into account when calculating aminoglycoside dose?
Volume status (concentration dependent killers)
How are aminoglycosides eliminated?
Unchanged by the kidneys
What is the peak concentration for gentamicin in gram-positive bacteria?
3-5
What is the trough concentration for gentamicin in gram-positive bacteria?
1
What is the peak concentration for gentamicin, tobramycin in gram-negative bacteria when treating UTI?
4-6
What is the peak concentration for amikacin in gram-negative bacteria when treating UTI?
20-25
What is the trough concentration for gentamicin, tobramycin in gram-negative bacteria when treating UTI?
0.5-1.5
What is the trough concentration for amikacin in gram-negative bacteria when treating UTI?
<8
What is the peak concentration for gentamicin, tobramycin in gram-negative bacteria when treating SSTI, bacteremia?
6-8
What is the trough concentration for gentamicin, tobramycin in gram-negative bacteria when treating SSTI, bacteremia?
1-1.5
What is the peak concentration for amikacin in gram-negative bacteria when treating SSTI, bacteremia?
25-30
What is the trough concentration for amikacin in gram-negative bacteria when treating SSTI, bacteremia?
<8
What is the peak concentration for gentamicin, tobramycin in gram-negative bacteria when treating pneumonia, burn, life-threat?
8-10
What is the trough concentration for gentamicin, tobramycin in gram-negative bacteria when treating pneumonia, burn, life-threat?
<2
What is the peak concentration for amikacin in gram-negative bacteria when treating pneumonia, burn, life-threat?
25-30
What is the trough concentration for amikacin in gram-negative bacteria when treating pneumonia, burn, life-threat?
<8
When do you use extended interval dosing?
Only in gram-negative
What is the peak concentration for gentamicin, tobramycin in intrabdominal infections, urosepsis, skin and soft tissue infections?
13-20
What is the trough concentration for gentamicin, tobramycin in intrabdominal infections, urosepsis, skin and soft tissue infections?
<0.5
What is the peak concentration for amikacin in intrabdominal infections, urosepsis, skin and soft tissue infections?
40-50
What is the trough concentration for amikacin in intrabdominal infections, urosepsis, skin and soft tissue infections?
<8
Plazomicin dosing
15 mg/kg IV IBW or ADW ever 24 hours if CrCl 60 or more
When is trough monitoring recommended in patients taking plazomicin?
In patients with CrCl 15-90
Aminoglycoside adverse effects
-Nephrotoxicity
-Ototoxicity
Risk factors for nephrotoxicity in aminoglycosides
-Prolonged high troughs
-Long duration of therapy
-Underlying renal dysfunction
-Elderly
-Hypovolemia
-Use of concomitant nephrotoxins
