Antibiotic Resistance Flashcards
What are the 4 main issues with antibiotic resistance?
β Increases mortality
β Challenges control of infectious diseases
β Threatens a return to pre-antibiotic era
β increases healthcare costs
β Jeopardizes health care gainst to society
What are βsuperbugsβ?
β Drug resistant bacteria that are not more pathogenic
β there are fewer options for treatment
How has S.aureus become resistant to penicillin?
β by acquiring a new PBP
What do gram +ve pyogenic cocci cause?
β Surgical sepsis
β endocarditis
What are enterococci naturally resistant to?
β Vancomycin resistant
Where do enterococci live?
β in the gut
Where do acinetobacter live?
β in the gut
How do vancomycin resistant MRSA arise?
β MRSA in the gut
β enterococci are vancoymycin resistant
β all the bacteria live together in the gut
β they exchange genes between each other and vancomycin resistant MRSA can arise
What are the 7 mechanisms of antibiotic resistance?
β Mutated target β New target β Efflux pumps β Intrinsic impermeability β Overproduction of target β Metabolic bypass β Drug inactivation
Why is MRSA not inhibited by beta lactams?
β it has acquired a new penicillin binding protein PBP2A so it is not inhibited by the beta lactam
How do efflux pumps work?
β new efflux pumps or upregulation of genes that code for efflux pumps
β they pump out antibiotics
How does intrinsic impermeability work?
β Membranes are naturally impermeable that they are resistant to a range of antibiotics without mutations
How does overproduction of the target work?
β Bacteria can overcome sulfonamides and trimethoprim by overproducing the target
β they upregulate genes that code for the enzyme so there is more enzyme than competitive inhibitor
How does metabolic bypass work with vancomycin?
β Vancomycin binds to terminal D-ala, D-ala
β the resistant bacteria have acquired a new biosynthetic pathway
β instead of generating D-ala, D-ala it maked D-ala lactate that vancomycin canβt bind to
How does a mutated target work?
β If RNA polymerase acquires a new mutation then the drug can no longer bind to it so the bacteria is resistant to rifampicin (TB)
β mutations in ribosomes and porins
β bacteria can acquire a gene for a completely new porin
How does drug inactivation work?
β beta lactamase destroys beta lactam and inactivates it
What are the mechanisms of natural resistance for gram + and -?
β Gram +ve peptidoglycan is highly porous and has no barrier to diffusion
β Gram -ve outer membrane forms a barrier
What is the Lamarck model for antibiotic resistance?
β Antibiotic is introduced and suddenly all the bacteria mutate
What is the right model for antibiotic resistance?
β There is a random mutation that occurs spontaneously
β lots of other mutations occur
β as soon as an antibiotic is added
β all the bacteria that do not have the mutation die off
β the mutants are the ones that are left
What are the chromosome mediated genetic mechanisms of antibiotic resistance?
β spontaneous mutation in the target molecule or the drug uptake system
What are the plasmid mediated genetic mechanisms of antibiotic resistance?
β common in gram -ve rods
β transferred via conjugation
β multidrug resistance
What are the three ways in which bacteria can take up genes?
β Transformation
β Transduction
β Conjugation
What is transformation?
β bacteria can take up bacterial DNA that has been lysed
What is transduction?
β bacteria can get infected by viruses (phage)
β the phage usually brings a piece of DNA from the previous bacterial host
What is conjugation?
βForming pili through which DNA is exchanged
β chromosomal DNA and plasmid DNA can be exchanged
How have gram +ve bacteria acquired resistance to beta lactams?
β Beta lactamase
β alteration of transpeptidase enzyme (PBP)
How have gram -ve bacteria acquired resistance to beta lactams?
β alteration of porins
What does augmentin/co-amoxiclav do?
β Binds to and inactivates beta lactamases
What is penicillin given with and why?
β Clavulanic acid
β is an inhibitor of a beta lactamase enzyme
β allows broad spectrum penicillin to work
What are the three ways in which a bacteria can become resistant to beta lactams?
β If the porin mutates or there is a new type of porin the beta lactam cannot enter
β the bacteria can encode a new PBP like MRSA and the beta lactam canβt bind to the new PBP
β bacteria can acquire a beta lactamase enzyme
What are the 4 ways in which bacteria become resistant to penicillin?
β Produce penicillinases/beta lactamases that cleave the beta lactam ring - penicillin is inactivated
β acquire alternative forms of/or mutations in PBPs so penicillin canβt bind
β acquire alternative forms of/or mutations in porins so penicillin canβt get into the cell
β acquire alternative forms of/mutations in efflux pumps so penicillins are pumped out faster
What is the only effective treatment for MRSA?
β Vancomycin
How is MRSA becoming resistant to vancomycin?
β Acquisition of the van operon by transposition
β makes D-ala D-lactate that prevents vancomycin binding
β because vancomycin recognises D-ala, D-ala
What are 2 non-genetic reasons that an antibiotic may be resistant?
β Inaccessibility to drugs
β Stationary phase/vegetations and biofilms
What kind of antibiotics donβt work on biofilms?
β inhibitors of cell wall synthesis
What kind of diseases are inaccessible to drugs?
β Abscess
β TB
What are 4 ways of preventing antibiotic resistance?
β Control use - not in animal feeds
β New or modified drugs
β combination therapy
β Infection control
What was the old treatment for gonorrhoea and why is this not used anymore?
β single intramuscular injection of penicillin
β 15% increase in resistance rates
What was the drug used after penicillin for gonorrhoea and why is this not used anymore?
β Ciprofloxacin (inhibits DNA gyrase)
β resistance rates increased
What is the new treatment for gonorrhoea?
β intramuscular injection of ceftriaxone + 1g azithromycin
What are carbapenems used for?
β broad spectrum antibiotics used as a last resort for gram -ve bacteria
What are CREs?
β carbapenem resistant enterococci
