Antimicrobial Flashcards
First question should always be
Should I be using an antibiotic (and..what am i treating)
Three classification of antibiotics
Classification by susceptible organisms
Classification by MOA
Classification by Type
Identify the likely pathogen
stains
serologies
culture and sensitivity
site
4 basic principles of therapy
know the drug confirm the presence of infection identify the likely pathogen select presumptive therapy monitor therapeutic response
You should see improvement in a patient within
24 to 48 hours
phamacokinetics
What the body does to the drug
– Concerned with the time course of antimicrobial
concentrations in the body
– Commonly used to determine dosing regimens
Pharmacodynamics
What the drug does to the body.
– Concerned with the relationship between those
concentrations and the antimicrobial effect.
– Increasingly important to design dosing regimens which
counteract or prevent resistance
is PK or PD determine dosing
PK
MIC
MIC: Minimum Inhibitory Concentration
the LEAST amount of drug that is required to kill or slow the organism
MBC
MBC: Minimum Bactericidal Concentration
Minimum that will kill the pathogen
Cmax
peak serum level after pt takes the drug
Cmin
least amount of drug you will see in the body
trough level
AUC
Area under the curve
puts all parameters together
Susceptibility testing
MIC
• Primary measure of antibiotic activity
– MIC is the lowest antimicrobial
concentration that
prevented prevented visible visible growth of an organism organism after 24 hours
of incubation
MIC is a good indicator
of the potency of an antibiotic
– It does not tell us about the time course of
antimicrobial activity
Breakpoints
Tells us the MIC/Zone values. Lets us know what which pathogens are susceptible, resistant or somewhat resistant
MIC90
tells you that 90% of strains of a particular pathogen are inhibited by this drug
PK Parameters help to do what
- Help to quantify the serum level time course of an antibiotic
- Evaluate antibiotic efficacy
Three most important PK parameters:
AUC, Cmax, Cmin
• Area under the curve is a
plot of concentration concentration of drug
in plasma against time
AUC represents
the total amount of drug absorbed by the
body regardless of rate of absorption
AUC is usefull in knowing the
g the average concentration over a
time interval
How high
peak level vs MIC
how long
time above MIC
how high for how long
ACU vs MIC
Peak/MIC
Cmax divided by MIC - will give you the formula for concentration antibiotic. How high does it need to be to irradicate the pathogen
Time>MIC
percentage of dosing interval in which the sum level exceeds the MIC
have to have the drug above a certain concerntraion for 40 to 50 % of dosing inverval in order to be effective
24 hr-AUC/MIC
24 hour AUC divided by the MIC
These drugs have a percisitant antbiotic effect
For a concentration (MAX) antibiotic we want to see that
the peak is 10x the MIC
for time dosing if you had a drug that was given 10 hours a part how long should the drug be over the MIC
40 to 50% or in this case 4 to 5 hours
The new science PK and PD
Is there an antibiotic level in blood that predicts bacterial
eradication and clinical success?
• If so, what is the optimal profile to maximize bacterial kill?
Once PK/PD requirements are known, one can: (3 things)
√ Calculate appropriate doses of new or existing agents
– √ Compare antimicrobial activity of existing agents and utilize
data in the development of guidelines
– √ Determine susceptibility of isolated pathogens
AUC/MIC ratioa at least what for gram pos an gram neg
25-30 pos
125 neg
Examples of Peak MIC drugs
aminoglycosides
examples of time dependent drugs
beta-lactums
clindamycin
erythromycin
linezolid
24-AUC/MIC drug examples (persistant)
azithromycin
quinolones
vancomycin
Examples of Multi-Drug Resistant Organisims
Strep pneumonaie
M hi illi Methicillin R i es stance S h tap aureus (MRSA CA (MRSA,CA‐MRSA)
– Vancomycin resistant enterococci (VRE)
– Some Gram negative organisms (MDR‐GNB)
Factors that Increase Antibiotic
Resistance
• Overuse of Antibiotics • Inappropriate antibiotics • Low dose… inadequate levels… subinhibitory exposure • Day Care and crowded living
Mechanisms of Resistance:
4 main types
- Decreased Permeability
- Antibiotic Efflux Pump
- Drug Inactivation
- Altered Target Site
Decreased permaiblity
lack of purions to get into the cell
Drug Efflux
eflux pumps, pump antibiotic out of the cell after they enter it
Drug inactivation
Enzymes inactivate the antibiotic
Altered Target
Changes that occur in the ribosomes
Beta‐lactamase
– Enzymes which destroy Penicillins and their
relatives
Beta‐Lactamase Inhibiting Compounds
Beta‐lactam antibiotics to which another
component (e.g. clavulanic acid added to
Amoxicillin) has been added to counteract the
beta‐lactamase
Cross-resistance
Genetic information may be passed from one
bacteria to another
Four types of cross resistance
– Mutation
– Conjugation
– Transduction
– Transformation
Conjugation
one bacteria shares dna with another bacteria
transduction
viral bacterial eats bacteria and shares DNA with it
Transformation
bacterial can incorporate dna from another organisim that is in the same enviornment. Bridge is not needed in this type
