Antimicrobial Resistance & Susceptibility Flashcards
antimicrobial resistance
the ability of a bacterium to survive and/or multiply when faced with a drug used to inhibit its growth and/or kill it
what are the outcomes of antimicrobial resistance
- drug is no longer effective
- increased animal disease and spread
- drug eliminates good pathogens but not the targeted pathogen
- use in animals can lead to resistance in humans
selective pressure
driving cause of antimicrobial resistance
antimicrobial kills off the bacteria that are susceptible and leave behind the ones that are resistant –> resistant population survives and grows
what are 4 mechanisms of bacteria use to become resistant
- pumping drug out of the bacteria
- preventing the entry of the drug into the bacteria
- inactivating the drug once inside
- changing the target site for the drug
intrinsic resistance
drug resistance that is naturally present in the microorganism
drug never has and never will work against the pathogen type
can NOT change this resistance - does not develop over time
acquired resistance
ability of a microorganism to survive and multiply in the presence of an antimicrobial that would normally inhibit/kill that organism
drug used to work but no longer does - develops over time
what are two methods of acquired resistance
- mutation
- acquisition
mutation
bacteria mutates its genetic code
rate of mutation increases with stress
acquisition
most common method
horizontal transfer of genes encoding resistance
- conjugation of plasmid
- transduction via bacteriophages
- transformation by up taking naked DNA
can acquisition of resistance occur between bacterial species
yes
how many resistant organisms does a normal population of bacteria have
very few - carrying around extra DNA is heavy
antimicrobial treatment will eliminate the susceptible bacteria and leave behind the resistant ones that will then proliferate to form a resistant population
antimicrobial susceptibility testing
method for determining if a bacterial isolate is susceptible to a range of antimicrobials that may be used to treat an infection with this bacteria
only a PREDICTION - not a guarantee
contraindications for susceptibility testing
- strain is predictably susceptible to certain antimicrobials
- infection type has high level of efficacy for empiric therapy (ex. first time UTIs)
- infection is highly mixed (will not provide useful information)
considerations for susceptibility testing
- location of infection
- breakpoints
- MIC
- zone of inhibition
how does location of infection impact susceptibility test result interpretation
test will predict if a particular drug will reach the tissue in concentrations high enough to inhibit bacteria
requires PK data to establish breakpoints specific for that location
breakpoints
cutoff values that determine the interpretation of MIC/zone of inhibition values as either susceptible, intermediate, or resistant
drug, host, and bacteria specific values
do all species have established breakpoints
no - must extrapolate from other species or body sites
not always appropriate/accurate
what drug concentration are breakpoints based off of
the concentration in the SERUM
MIC
minimum inhibitory concentration
lowest concentration of antimicrobial drug that inhibits growth of a bacterium (ug/mL)
zone of inhibition
diameter of bacterial growth that is inhibited around an antimicrobial disk
what are the three methods of AST
- broth micro dilution
- E-test
- disk diffusion
broth micro dilution
measures MIC
culture gets isolated and inoculated into broth –> placed into wells –> variable concentration of different drugs added to wells (drugs based off of panel type) –> check for growth
broth micro dilution results
- no growth achieved at a specific concentration –> compare to breakpoint to determine if S, I, or R
- MIC = lowest concentration that achieved no growth - growth achieved at all concentrations –> resistant
- MIC > highest concentration - no growth achieved at any concentration –> susceptible
- MIC < lowest concentration
what does NA, NI, or NN mean on a susceptibility report
no information provided to categorize as S, I or R
what are the pros of broth microdilution
- gets an MIC
- has standardized breakpoints
- works for some slow growing or fastidious organisms
what are the cons of broth microdilution
- more expensive
- need special equipment
e-test
antimicrobial strip testing
measures MIC
disk diffusion
measures zone of inhibition
standardized lawn of bacteria spread over plate –> filter paper disks with antimicrobial applied to lawn –> incubate –> check for zone diameter of inhibition
disk diffusion result interpretations
S, I, or R depending on zone size, drug, and host species
pros of disk diffusion
- easy
- inexpensive
- no special equipment
- more flexibility with drugs used
cons of disk diffusion
- no MIC measured
- doesn’t work for slow growing/fastidious organisms
AST interpretation
categorization based on breakpoints established for host, drug, and organism based on the MIC or zone diameter
used to determine whether a drug can be used to treat an infection
susceptible
bacterial isolate is inhibited by usually attainable concentration of drug for infection site
MIC </= susceptibility breakpoint
intermediate
MIC approaches the usually attainable concentration levels for susceptible isolates
clinical efficacy might be achieved in body sites where the drug concentrates
MIC = intermediate breakpoint
resistant
bacterial isolate is not inhibited by the usually achievable concentrations of antimicrobial
MIC >/= resistant breakpoint
effect of susceptibility report on drugs that reach greater concentration at the target site than in serum
susceptibility test will UNDERESTIMATE true susceptibility
ex. topical administration for skin infections or UTIs
effect of susceptibility report on drugs that reach lower concentration at the target site than in serum
susceptibility test will OVERESTIMATE true susceptibility
ex. intracellular bacteria, eye, prostate
does “no interpretation” mean that drug will not be effective
NO - only means that efficacy can’t be predicted
is an interpretation of resistance or susceptibility more likely to be correct
resistance
R is more likely to correctly predict failure of the drug to work than S is likely to predict success of the drug
