Micro: Antimicrobial Resistance Flashcards
(37 cards)
Name/define the two forms of antimicrobial resistance.
Innate - existence before exposure to the drug.Acquired - antibiotic use-driven selection and accumulation of resistant strains
Name four examples of innate resistance. How does these resistances work?
G+ bacteria resistant to polymyxins; lack of lipopolysaccharide layer (LPS) G- bacteria resistance to vancomycin; vancomycin too large to cross thick outer membrane Intracellular bacteria to b-lactams; b-lactams poorly absorbed by animal cells Chlamydia and mycoplasma to b-lactams; both bacteria lack peptidoglycan cell walls
Name the 5 basic principles of antibiotic resistance.
- Resistance will likely emerge given sufficient time/drug use 2. Antibiotic resistance is progressive. 3. Bacteria resistant to one drug are most likely to become resistant to other drugs. 4. If resistance is present, it’ll decline slowly if at all. 5. Anti-biotic use affects those in immediate and extended healthcare environment.
What is a bactericidal agent? What situations would be use bactericidal agents?
Bactericidal = causes cell death Used during chronic infections and infections known to create biofilms.
What is a bacteriostatic agent?
Bacteriostatic = slows cell growth
How do bacteriostatic agents clear infections if they only slow bacterial growth?
They don’t clear infections. They slow infections to control them until the immune response can clear them.
What general class of antibiotics are bacteriostatic? What is one member of this class that is bactericidal?
All protein synthesis inhibitors are bactiostatic EXCEPT aminoglycosides, which are bactericidal.
Define MIC.
MIC = Minimum inhibitory concentration. It is the lowest concentration that a drug must achieve to inhibit growth of a certain bacterium.
Define Breakpoint.
Breakpoint = the MIC that defines whether a bacterium is susceptible or resistant to a drug.
Use MIC and breakpoint to define if a bacterium is resistant, susceptible, or intermediate to a drug.
Resistant = If the breakpoint of a drug for a bacterium is below or equal to its MIC. Susceptible = if the breakpoint is above the MIC Intermediate = if the breakpoint is resistant for some measurements and susceptible for others.
Define MBC.
MBC = minimum bactericidal concentration. Its the lowest concentration that a drugs much achieve to kill a certain bacterium.
Name/Define the 6 indications to use multi-drug therapy
- Probable synergy – the two drugs we’re prescribing have shown to work together for a stronger effect 2. Polymicrobial infection – there’s more than one microbe and have to treat with more than one antibiotic 3. Uncertain diagnosis – we’re not entirely sure what the bacterium is, so let’s hit it from a few angles 4. Reduction in emergence of resistance – a bacterium will struggle to adapt to two or more drugs at the same time, so we can reduce the chance of resistance emerging 5. Reduction of therapeutic levels of toxic drug – a drug that is toxic at therapeutic levels by itself can be made therapeutic and non-toxic at lower levels in conjunction with another drug (not entirely sure on this one, edit later) 6. Organ coverage (eg, access to CSF) - not entirely sure on this one, edit later
Name/define the three general mechanisms of antibiotic resistance.
- Exclusion - resistance born from excluding the antibiotic from the bacterium’s cytoplasm 2. Altered target - somehow changing the drug’s target to inhibit binding 3. Enzymatic inactivation - producing an enzyme to inactivate a drug.
What is the most robust mechanism of resistance?
Enzymatic inactivation is the most robust form of resistance because no sacrifice in activity must be made.
What are the two types of exclusion?
Innate and Acquired exclusion
Give three types of acquired exclusion resistance mechanisms.
- Altered membrane lipids - reduce drug binding/diffusion 2. Altered porins or transport properties - make it more difficult for antibiotics to enter the bacterium. 3. Increase efflux pump expression - increasing the ability to actively pump out antibiotics. Seen in tetracycline resistance and often seen in multi drug resistance. Induced by drug presence
What are the two types of altered target resistance?
- Amino acid substitutions to reduce affinity for antimicrobial agents. 2. Acquisition of new activity to altered the drug’s target.
What limits the range of mutation that can occur in altered target resistance?
Functionality. The altered binding sites have to still function for the bacterium for it to thrive, so it can only change so much.
How are newer antibiotics designed to combat altered target resistance?
New drugs are designed to bind to multiple sites so if one site is altered, it can still be efficacious at another site.
(left) Which antibiotics are this bacterium resistant? Susceptible? (right) What is the plate on the right testing?
(left) This Kirby-Bauer test shows it’s definitely resisting A and C. Its resistant to D and F to a some degree. Its susceptible to B, E, and G. (right) This E-strip is testing different concentrations of an antibiotic to see what concentration is efficacious.
Name the two types of enzymatic inactivtion; give examples of each.
Antimicrobial destruction - cleavage or some other method of destroying the enzyme to inactivate it.
Ex) b-lactamases
Antimicrobial modification of hydroxyl or amino groups
Ex) acetylation, adenylation, or phosphorylation
Which mechanisms are used in resisitance of antimicrobials that target the cell wall?
All three (exclusion, altered target, inactivation)
How to Gram- bacteria use exlcusion to combat cell antimicrobial agents? Are they innate or acquired?
Penecillins - combination of poor uptake and efflux pump expression
Vancymycin - outer membrane porins are not large enough to accomodate this drug’s entry
Thse bacteria may also modify their porins to acquire b-lactam exclusion.
How does Staph aureus (G+) use exclusion to combat vancomycin?
Can increase the thickness of its cell wall to exclude vancymycin from the cell wall precursors that it attaches to and trap vancomycin in the cell wall.
