Antibiotic Resistence Flashcards
Why is antibiotic resistance a global concern?
Increases mortality
Challenges control of infectious diseases
Threatens a return to the pre-antibiotic era
Increases the cost of health care
Jeopardises health care gains to society
What is superbugzilla?
When microbacteria in the same environment can exchange genes and pass on resistance to one another
For example enterococci giving MRSA vancomycin R+ resistance in the gut
What are the main mechanisms of antibiotic resistance?
Drug in activation - eg. beta lactimase
Altered or new target - eg. Ribosome, porin, RNA polymerase
Metabolic by pass - eg. vancomycin
Efflux pump - over activation so antibiotics are pumped out faster than they can get in
overproduction of target - eg. Trimethoprim - overproduced folic acid overcoming the inhibition
Intrinsic permeability - intrinsically impermeable to the antibiotic
What are the four pathways to resistance?
Directed at antibiotic itself - degrading drug or modifying drug
Now or altered target - antibiotic no longer binds
Altered transport
Metabolic by pass
What are the three mechanisms of resistance?
Natural resistance
Genetic mechanisms - acquired
Non genetic mechanisms - tolerance
What happens during natural resistance?
Drug must reach target by passing through natural barriers
G+ peptidoglycan - highly porous - no barrier to diffusion
G- outer membrane - barrier resistance advantage
What are the two genetic ways bacteria can become resistant?
Chromosome mediated
- due to spontaneous mutation in the target molecule or drug uptake system
Plasma mediates gene exchange
- common in G-
- multidrug resistence
- transferred by conjugation
How can genes be transferred between bacteria?
Transformation
- fragment of DNA from another bacterial cell enters a bacteria and joins the bacterial chromosome
Transduction
- fragment of DNA from another bacterial cell in a phage fuzes with a bacteria and joins with the DNA
Conjugation
- two bacteria join together using sex pilli and genes are transferred from the donor cell to the recipient cell
How can different bacteria build resistance to beta lactams?
Gram +ve: alteration of transpeptidase enzyme
Gram -ve: alteration of porins
What does penicillinase do?
Destroys active part of penicillin molecule - cleaves off beta lactam ring
How does Augmentin function?
Made of Clavulanic acid and amoxicillin
Binds to and inactivates beta lactimases
No antibacterial activity of its own
What are the mechanisms by which bacteria can become resistant to penicillin?
Produce penicillinases that cleave the beta lactam ring - penicillin is in activated
Acquire alternative forms of mutations in penicillin binding protiens - penicillin can’t bind
Acquire alternative forms of mutations in porin - penicillin cannot get into cell
Acquire alternative forms of mutations in efflux pumps - penicillin’s are pumped out faster
What is a antibiotic for MRSA?
Only effective treatment is vancomycin
It stops the bacteria from making peptidoglycan
What are non genetic mechanisms that allow for bacterial resistance?
Inaccessibility to drugs
Stationary phase/vegetations and biofilms
How can we prevent or overcome antibiotic resistance?
Control use - appropriate prescribing
New or modified drugs
Combination therapy - different targets overcome mutation rates
Infection control
