clinical PKs of AGs and vancomycin

Question 1

aminoglycosides spectrum of activity

Answer 1

no anaerobes
gram-negative aerobes: enterobacteriaceae, P. aeruginosa (tobramycin), acinetobacter species
gram-positive aerobes* (more often): primarily used in combination with a cell wall-active agent for synergy (gentamicin - never monotherapy), staphylococci, streptococci, enterococci

Question 2

aminoglycoside PKs

Answer 2

must be administered parenterally**; usually infused over 30-60 minutes
primarily distributed into extracellular fluid
primarily excreted exchanged by glomerular filtration
normal half-life: 2-3 hours*
removed by hemodialysis (10% per hour)

Question 3

aminoglycoside PDs

Answer 3

exhibit conc-dependent bactericidal activity**

• PD parameter: peak/MIC ratio
• optimal peak/MIC ratio 8-10:1

Question 4

aminoglycoside dosing recommendations

Answer 4

loading dose:
-gentamicin, tobramycin: 2-2.5** mg/kg
-amikacin: 7.5 mg/kg
maintenance dose (based on renal fxn):
-gentamicin, tobramycin: 1.5-2 mg/kg q8-12h (normal renal function)
-amikacin: 5-7.5 mg/kg q12h (normal renal fxn)

Question 5

target peak and trough conc for gram-negative infections

Answer 5

maximize peak/MIC ratio
moderate: UTI
-Gentamicin, tobramycin: peak 4-6; trough less than 1
-amikacin: peak 20-25; trough 4-8
moderate-severe: osteomyelitis, pyelonephritis, soft-tissue infections
-gentamicin, tobramycin: peak 6-8; trough less than 1
-amikacin: peak 25-30; trough 4-8
severe: bacteremia, pneumonia, life-threatening infections
-gentamicin, tobramycin: peak 8-10; trough less than 1
-amikacin: peak 25-30; trough 4-8

Question 6

target peak and trough conc for gram-positive infections

Answer 6

synergy*** (must be used in combination) for gram-positive infections - not as concerned about peak/MIC d/t synergy
-combination with cell-wall agent for staphylococcal, streptococcal or enterococcal infections
-gentamicin - preferred agent
---target peak: 3-5**
---target trough: less than 1**
examples:
-nafcillin + gent - MSSA
-vancomycin + gent - MRSA or entercocci
-ampicillin + gent - enterococci

Question 7

serum conc monitoring

Answer 7

obtain peak and trough conc at steady state (usually 4-6 half lives - 3rd or 4th dose)
peak conc should be obtained at least 0.5 hour after the end of a 0.5-1 hour infusion (after distribution phase* is complete)
Trough conc should be obtained less than 0.5 hours before the next dose***
Why wait to obtain peak after distribution phase? if not, you will calculate k incorrectly (overestimate elimination rate)

Question 8

traditional aminoglycoside dosing in clinical practice

Answer 8

population pharmacokinetic dosing to calculate INITIAL* aminoglycoside dosing regimen
utilize PK parameters derived from a “population” of patients to estimate PK parameters in a specific patient - “average”
populaiton parameters were generated from older studies and patient parameters may vary* from your specific patient

Question 9

IBW equation

Answer 9

males = 50 kg + 2.3*inches over 60
females = 45.5 kg + 2.3*inches over 60

Question 10

adjusted body weight equation

Answer 10

IBW + 0.4(TBW-IBW)

calculate if TBW is over 1.3(IBW)

Question 11

lean body weight dosing

Answer 11

calculate if patient is morbidly obese (BMI over 40)
males = (9260TBW)/((216BMI)+6680)
females = (9270TBW)/((224BMI)+8780)

Question 12

CrCl equation

Answer 12

(140-age)weight/(SCr72)

multiply by 0.85 for females

Question 13

weights used while dosing aminoglycosides

Answer 13

CrCl: TIIL
V(L) : TIAA
EID: TIAA

Question 14

choosing volume of distribution range

Answer 14

0. 25 L/kg = normal
1. 15-0.20 L/kg = dehydrated
2. 30-0.35 L/kg = used most often - fluid overload, burn, pregnancy, critically ill, infection

Question 15

cmax and cmin

Answer 15

Cmax = desired max conc
Cmin = desired min conc
NOT peak or trough

Question 16

cmax or peak larger??

Answer 16

Cmax!!!

Question 17

delta t

Answer 17

time between Cpk and Ctr and is calculated as (tau) - (tinf) - (time from end of infusion of Cpk) - (time from Ctr to next infusion)

Question 18

extended interval dosing of aminoglycosides

Answer 18

higher peak
maximize conc-dependent bactericial** activity by giving larger doses
minimize accumulation in target organs - conc should be zero at 24 hours
dosing interval based on CrCl
hartford nomogram - obtain single random blood sample 6-14 hours after START of infusion on day 5 - puts point near line

Question 19

vacnomycin PD target

Answer 19

AUC/MIC = 400

Question 20

weight dosing in vancomycin

Answer 20

based on TBW

not well defined in morbid obesity

Question 21

V(L) for vancomycin

Answer 21

0. 6-0.7 L/kg using TBW in non-morbidly obese

0. 6-0.7 L/kg using ABW in morbidly obese

Question 22

cpk and ctr for vancomycin dosing

Answer 22

Cpk (or Cmax): 30-40 mg/L

Ctr (or Cmin): 10-15 mg/L or 15-20 mg/L depending on site and severity of infection

Question 23

vancomycin monitoring parameters

Answer 23

“optimal” - trough serum concentrations
-always maintained about 10 mg/L
-if the MIC is 1 mg/L, Cmin of 15 mg/L should achieve target AUC/MIC of 400
troughs of 15-20 mg/L recommended in complicated infections (endocard, osteomyel, meningitis, MRSA, pneumonia)

Question 24

calculating AUC

Answer 24

(lin trap + log trap) *2