Pharmacokinetics and Dynamics of Antimicrobial Drugs Flashcards
What is MIC? How does it compare to MBC?
MIC is the mean inhibitory concentration and is the amount of drug needed to stop bacterial growth.
MBC is mean bactericidal concentration and is the concentration at which 99.99% of bacteria are killed
What is “breakpoint”?
The concentration of antibiotic below which the bacteria is susceptible
What is post-antibiotic effect?
Persistent suppression of microbial growth after the removal of antibiotics from the medium (used for aminoglycosides to reduce ototoxic and nephrotoxic effects)
What is time-dependent killing?
How does it compare to concentration-dependent killing?
The mechanism of bacterial killing depends on the amount of time where the concentration is above the MIC whereas concentration dependent killing is the mechanism of killing depends on the peak concentration (Cmax) above the MIC and NOT the time
What three factors determine the outcome of an infection?
- characteristics of the infecting organism (innate susceptibility to antimicrobials/acquired resistance)
- Characteristics of the host- site of infection
- Choice of appropriate antimicrobial therapy
What is susceptibility testing?
What type of infection are they used for?
What can it not be used for?
Testing done in a micro lab to get an idea about what antimicrobials might treat an infection.
Used for bacteria and yeasts
Not used for moulds or parasites
What are the three main susceptibility tests?
- Broth dilution- inoculate a tube containing a defined inoculum with bacteria and test different concentrations of antimicrobial of interest. Measure turbidity of the broth. MIC is where growth is inhibited completely
- Kirby-Bauer Disk Diffusion- place antibiotic impregnated disk on agar plate that has been inoculated with a bacteria lawn. Measure zone of inhibition of growth. Larger diameter= better
- E-test= lab tech places a strip which has a gradient of increasing antimicrobial concentration. Where the zone of growth inhibition starts will align with the MIC
Why is MIC used more commonly than MBC when doing susceptibility tests?
Because MBC requires doing viable counts and plating bacteria or yeast on agar plates and is labor-intensive
What are the three ways a bacteria can be reported from susceptibility testing?
- susceptible- standard dosage of antimicrobial will be effective at treating infection
- Intermediate- antimicrobial may be effective at high enough concentrations
- Resistant- growth could not be inhibited by concentrations within the therapeutic index for the drug
A bactericidal drug will kill over _______ of the bacteria in the solution over a 24 hour period. This is known as a greater than ______log kill.
99.99%
greater than 3 log kill
(99%-2logs killed is bacteriostatic)
What are the major bactericidal drugs?
- Penecillin/Cephalosporins/carbopenems
- Fluoroquinolone
- Aminoglycoside
- Vancomycin
- Daptomycin
- Metronidazole
- Rifampin
What are the major bacteriostatic drugs?
- tetracycline
- sulfanomides
- macrolides
- clindamycin
- linezolid
What is the “90-60” rule?
What does this tell us about host factors?
Infections susceptible to antimicrobials work 90% of the time.
Infections resistant to antimicrobials work 60% of the time.
This tells us that host factors are critical in determining outcome more than just knowing MIC
Susceptibility testing is more likely to help us______________________ than to select ______________________.
rule out drugs that are least likely to succeed than to select ones that will work
What are the only 2 anti-fungal drugs to undergo renal excretion?
- amphotericin
- fluconazole
All the rest are hepatic with biliary or renal excretion of metabolites
