Aminoglycosides

Question 1

Aminoglycosides

Answer 1

-ultimately involves the inhibition of protein synthesis –> bactericidal

Question 2

Aminoglycosides activity

Answer 2

-gram-neg (enterobacterales_
-gram-pos (occi)

Question 3

Aminoglycosides admin

Answer 3

-must admin parenterally for systemic infections
-usually IV over 30-60 min
-may be given IM (not if septic, HYPOtension) Tmax
-Tmax longer if IM (2 hours)

Question 4

Aminoglycosides distribution

Answer 4

–extracellular fluid

Question 5

Aminoglycosides excrection

Answer 5

-unchanged by glomerular filtration (accumulates in urine)
-removed by hemodialysis (10%/hr)

Question 6

Aminoglycoside half-life

Answer 6

-2-3 hours

Question 7

Aminoglycoside PD

Answer 7

-concentration-dependent activity
-Peak/MIC= 10:1
-AUC/MIC ~30-50 normal pt
-AUC/MIC ~80-100 if monotherapy or high bacterial burden

Question 8

Aminoglycoside loading dosing

Answer 8

-gentamicin, tobramycin: 2-2.5 mg/kg
-Amikacin: 7.5 mg/kg

Question 9

Aminoglycosides Maintenance dose

Answer 9

-Gentamicin, Tobramycin: 1.5-2 mg/kg q8-12h
-Amikacin: 5-7.5 mg/kg q12h

Question 10

Target peak of gram neg UTI

Answer 10

-G/T: 4-6 mcg/mL
-A: 20-25 mcg/mL

Question 11

Target peak aminoglycosides for mod-severe

Answer 11

G/T: 6-8 mcg/mL
-A: 25-30 mcg/mL

Question 12

Target peak aminoglycosides for severe

Answer 12

-G/T: 8-10
-A: 25-20

Question 13

Target trough aminoglycosides gram neg

Answer 13

-0.5-1
-4-8

Question 14

Synergy for gram pos infections

Answer 14

-combo w cell wall-active agent for staph, strept, entero
-prefer gentamicin

Question 15

Gentamicin

Answer 15

-preferred agent for gram pos
-peak: 3-5
-trough <1

Question 16

Aminoglycoside concentration monitoring

Answer 16

-obtain peak/trough at steady state (4-6 half lives)
-obtain peak at least 0.5 hours after the end of a 0.5-hour infusion (after distribution)
-Trough should be obtained < 0.5 hours before the next dose

Question 17

Why wait to obtain peal after distribution phase?

Answer 17

-

Question 18

Traditional dosing in practice

Answer 18

-POPULATION dosing to calc initial aminoglycoside dosing regimen
-utilize PK parameters derived from a population of pt to estimate parameters

Question 19

Aminoglycoside dosing steps

Answer 19

1. select Cmin and Cmax based on site/severity of infection
2. IBW, AdjBW, LBW
3. Cockcroft
4. Population estimate using k
5. half-life
6. Vd
7. tau
8. MD
9. double check
10. AUC

Question 20

Aminoglycoside dosage timing

Answer 20

-extremely important to VERIFY TIMING of admin of previous/current doses
-PRIOR

Question 21

Extended-Interval Dosing (EID) of aminoglycosides

Answer 21

-max concentration-dependent vactericidal activity by giving larger doses (less freq) (max peak/MIC)
-give dose q24h to pt with normal renal funtion!!
-minimize toxicity, resistance
-may not apply to all

Question 22

EID dosing

Answer 22

-G/T: 5-7 mg/kg as single dose
-A: 15-25 mg/kg
-G/T: 15-20 mcg/mL Cmax
-A: Cmax 50-60 mcg/mL Cmax
-trough undectable!!

Question 23

Dosing interval based on CrCL

Answer 23

-> 60ml/min q24h
-40-60 ml/min q36h
-20-39 ml/min q48h
-< 20 ml/min use trad dosing

Question 24

Hartford Nomogram

Answer 24

-inability to calc pt-specific PK