PD

Question 1

Pharmacodynamics

Answer 1

Refers to the manner in which antibiotics interact with their target organisms to exert their effects

Question 2

Susceptibility Testing

Answer 2

MIC- minimum inhibitory concentration for the organism-antibiotic combo

For each combo, there is a particular cutoff MIC that defines susceptibility- called the breakpoint

Antibiotic MICs for a single organism generally should not be compared across different drugs (different antibiotics achieve different concentrations in the body in different places)

Used to be done in test tubes; now more commonly on microdilution plates or automated systems
Standard concentration of organism that patient had grown combined with increasing concentrations of antibiotic

Broth dilution methods are considered gold standard
Other methods exist (disk diffusion and E-tests)

Question 3

Static vs Cidal

Answer 3

At MIC, antibiotic is inhibiting growth

Bacteriostatic- inhibit growth of organism without killing it
If antibiotics removed, it will start growing again
Allow the patient’s immune system to catch up and kill off the organism

Bactericidal- kills the organism without help from the immune system
Preferred for certain infections (endocarditis, meningitis, infections in neutropenic patients, possibly osteomyelitis); immune system may not be as effective in these infections due to anatomic location or immunosuppression of patient

MBC- minimum bactericidal concentration- 99.9% (3-log) reduction in the original bacterial inoculum

When MBC is 4x or less than MIC, drug considered cidal
If greater, then considered static

MBC testing is more difficult; not common

Whether drug is cidal or static can vary based on pathogen, achievable dose, and growth phase of the organism

Question 4

Cidal Drugs

Answer 4

Penicillins
Cephalosporins 
Carbapenems
Monobactams 
Vancomycin (slowly)
FQ
AMG
Metronidazole 
Daptomycin

Question 5

Static Drugs

Answer 5

Macrolides
Tetracyclines
Linezolid

Question 6

PK/PD Relationships

Answer 6

Antibiotics differ in how they manifest their effects over time

Time dependent activity- activity against organisms correlates with duration of time that the concentration of drug remains above MIC

Concentration dependent or time independent- activity correlates with ratio of peak concentration of drug to MIC

For some, area under concentration curve AUC-MIC is best predictor of success

AMG now frequently given as a single large dose daily to leverage concentration dependent activity
Beta lactams given as continuous infusions or prolonged infusions because of time dependent activity

Question 7

Time > MIC Drugs

Answer 7

Penicillins
Cephalosporins
Carbapenems
Monobactams

Question 8

AUC/MIC Drugs

Answer 8

Vancomycin

Macrolides
Tetracyclines
Linezolid

Question 9

Peak:MIC Drugs

Answer 9

FQ
AMG
Metronidazole
Daptomycin