antimicrobial pharmacodynamics

Question 1

PK vs PD in antibacterial therapy

Answer 1

PK - conc vs time in tissue or other body fluids or at site of infection
PD - pharmacologic or toxologic or antimicrobial effect

Question 2

B-lactam PDs

Answer 2

correlation with clinical and microbiologic outcomes - time that free drug concentration remain above the MIC (fT>MIC)**
antibacterial properties: not rapidly bactericidal, time-dependent bactericidal activity (concentration-dependent up to 4x MIC), short-to-no postantibiotic effect for gram-negative pathogens - exceptions: carbapenems
-postantibiotic effects: continuous inhibition or killing of bacteria while antibiotic not present

Question 3

time vs conc dependent bactericial activity

Answer 3

b-lactam (time dependent) - all concentrations showed similar rates of killing, all required time to show major effect
AG and FQ (conc dependent) - major difference between concentrations when looking at number of organisms at 2 hours after 1 dose

Question 4

optimal dosing strategy for beta-lactam antibiotics

Answer 4

maximize fT>MIC (as a % of dosing interval)
-gram negatives: carbapenems over 40% (post-AB effect), penicillin over 50%, cephalosporins over 60%
-gram-positives: over 40-50%
strategies to maximize fT>MIC
-increase dose, same interval
-same dose, shorter interval
-continuous infusion
-prolonged infusion (dec. mortality, LOS, ventilation days, cost)

Question 5

FQ PDs

Answer 5

correlation with clinical and microbiologic outcomes - fAUC0-24/MIC ratio
antibacterial properties
-rapidly bactericidal
-conc dependent bactericidal activity
-postantibiotic effect for both gram-positive and gram-negative bacteria

Question 6

optimal dosing strategy - FQs

Answer 6

maximize free AUC0-24/MIC ratio
desirable targets
-over 100 for gram-negative pathogens
-30-40 for gram positive pathogens (100??? prevent emergence of resistance)

Question 7

AG PDs

Answer 7

correlation with clinical and microbiologic outcomes - Peak/MIC ratio
antibacterial properties:
-rapidly bactericidal
-conc-dependent bactericidal activity
-postantibiotic effect for both gram + and gram - bacteria
-adaptive resistance - down-regulation of AG transport into bacteria when no drug-free interval exists

Question 8

summary of PK/PD**

Answer 8

T>MIC - B-lactams*
Peak/MIC - aminoglycosides, daptomycin, metronidazole
AUC0-24/MIC - clindamycin, daptomycin, doxycycline, FQs, linezolid, macrolides, metronidazole*, tigecycline, vancomycin

Question 9

equation to estimate T>MIC for B-lactams

Answer 9

only 2 variables are V and CL - all other values are constant between all patients