Antibiotic Resistance Flashcards
Where did most antibiotic resistance most likely emerge from
overuse of antibiotics in agriculture
misuse of antibiotics in humans: 50% inappropriate use, wrong dosage or duration such as in a viral infection
there are 25 million pounds of non therapeutic livestock use and there are about 3 million pounds of human medical use
What does MDR stand for
multidrug resistant
resistant to three or more antibiotic categories
How many antibiotics are MDR (multi drug resistant) bacteria resistant to
resistant to three or more antibiotic categories
What does XDR stand for
extensively drug resistant
susceptible to two or fewer antibiotic categories
only two or one antibiotic category would work
What does PDR stand for
pan drug resistant
not susceptible to any of the approved drugs in all categories
How many antibiotics are XDR (extensively drug resistant) bacteria resistant to
only susceptible to two or fewer antibiotic categories
How many antibiotics are PDR (pan drug resistant) bacteria resistant to
not susceptible to any of the approved drugs in all categories
There are the 6 well known multi drug resistant pathogens
Enterococcus spp. VRE
Staphylococcus aureus MRSA
Klebsiella spp. CRE
Acinetobacter baumannii ESBL
Pseudomonas aeruginosa ESBL
Enterobacter spp. CRE
What are the main mechanisms of antibiotic resistance
- restriction of the antibiotic to the antibiotic target
- enzymatic inactivation of the antibiotic
- modifying the antibiotic target
- protecting the antibiotic target
- failure to activate the antibiotic
- restriction of access to target: outermsmbrane barrier, selective porins, efflux pumps
- enzymatic inactivation: beta-lactamase, aminoglycoside modifying enzymes, CAT
- target modification or protection: PBPs with reduced affinity for beta lactase, point mutations that alter affinity of DNA gyrase to fluoroquinolone, RNA polymerase mutations alter affinity to rifampin, 23S rRNA mthylases, D-ala-D-lac substations
- failure to activate the antibiotic: metronidazole is a prodrug requiring reduction by bacterial flavodoxin to active form, reduced expression to flavodoxin
What are examples of restriction of the antibiotic to the antibiotic target
outer membrane barrier
selective porins
efflux pumps
What are examples of enzymatic inactivation of the antibiotic
beta-lactamase
aminoglycoside modifying enzymes
CAT
How do outer membrane porins work against antibiotics
outer membrane: formidable barrier
outer membrane porins are selective gatekeepers
How do outer membrane porins work against antibiotics
outer membrane: formidable barrier
outer membrane porins are selective gatekeepers
small molecules can diffuse to periplasm through porins
antibiotics such as vancomycin and daptomycin are too large to get through porins and the outer membrane
What types of antibiotics do porins prevent/ how does this process work/ what type of antibiotic resistance is this
vancomycin and daptomycin are too large to diffuse through the periplasm through porins
usually small molecules diffuse through porins into the periplasm
restriction of access of the antibiotic to its target
How do antibiotic efflux pumps work against antibiotics
efflux pumps have been discovered for nearly every class of antibiotic
gram - efflux pumps span both membranes and is analogous to type I secretion system
gram + efflux pumps are simple anti-porters or ABC transporters
What type of efflux pump do gram - bacteria have
span both membranes and is analogous to type I secretion system
What type of efflux pump do gram + bacteria have
are simple anti-porters or ABC transporters
An efflux pump is a type of ____ antibiotic resistance mechanism
restriction to access of the antibiotic to its target
How do serine beta-lactamases work against antibiotics
cleave the beta-lactam ring of antibiotics
similar mechanism to the beta lactams action on the transpeptidase enzyme
Are serine beta-lactamases more common in gram - or gram +
more common in gram negative bacteria
How do zinc beta-lactamases work against antibiotics
cleave the antibiotic at a different site
clavulanic acid and other inhibitors cannot interact with the zinc form
can cleave a wider range of beta lactams than serine beta-lactamases
used against Carbapenems: Doripenem, Meropenem, Imipenem
What does clavulanic acid do
inactivates beta-lactamase in when added with SERINE beta-lactamases used with penicillin, cephalosporins: Ceftazidime, Cefotaxime, Ceftriaxone???
clavulanic acid and other inhibitors cannot interact with the ZINC form
When is clavulanic acid usually administered with
beta lactams can be administered in combination with a beta lactase inhibitor bc the clavulanic acid inactivates beta lactamases in SERINE beta lactamases
clavulanic acid and other inhibitors cannot interact with the ZINC form
What type of antibiotic resistance mechanism do serine beta lactamases and zinc beta lactamases
enzymatic inactivation
