AntiR Flashcards
Why is resistance a global concern?
→Increases mortality
→challenges control of infectious diseases
→threatens a return to the pre-antibiotic era
→increases the costs of health care
→jeopardizes health-care gains to society
What are beta lactamase?
→enzymes produced by bacteria that break open the beta-lactam ring, inactivating the beta-lactam antibiotic
What is methicillin?
→lactamase resistant penicillin
What is MRSA?
→methicillin-resistant Staphylococcus aureus
What 2 factors lead to vancomycin resistant MRSA?
→Co-infection
→genetic exchange
Examples of syperbugzillas?
→Enterococci - G+ve
→Acinetobacters- G-ve
→MRSA- G+ve
What are the mechanisms of antibiotic resistance?
→Drug inactivation →Altered or new target →Metabolic by-pass →Efflux pump- pump drug outside of cell →Intrinsic impermeability →Overproduction of target- increased folic acid
What features of protein synthesis can be a source of resistance?
→Ribosome →Porin mutations so antibiotic can’t get through →PBPs – peptidoglycan synthesis →DNA gyrase →RNA polymerase →Mcr1 & colistin
Why can efflux pumps increase resistance?
→by acquisition of pumps
→mutations or over expression
What can be overproduced as a mechanism of antibiotic resistance?
→precursor trimethoprim
What are the different paths to resistance?
→Directed at antibiotic itself
→New or Altered target
→Altered transport- excess pump
→Metabolic by-pass- metabolic change D-ala-D-lac and vancomycin
What are the three types mechanisms of resistance?
→Natural resistance
→Genetic Mechanisms - acquired
→Non-Genetic Mechanisms (growth phases) tolerance
What structure in the cell wall of bacteria results in multiple resistance?
→Porins
What are the two genetic mechanisms of resistance?
→Chromosome-mediated
→Plasmid-mediated gene exchange
Describe chromosome-mediated resistance
→spontaneous mutation:
→in the target molecule
→in the drug uptake system
→Mutants are SELECTED; they are NOT induced
Describe plasmid-mediated gene exchange for resistance
→Common in Gram-negative bacteria
→Transferred via conjugation
→Multidrug resistance
Which bacteria is known to have many mutations?
→e.coli
What are the mechanisms of gene transfer in bacteria?
→transformation
→transduction
→conjugation
Describe bacteria transformation
→fragment of DNA from another bacterial cell is incorporated into bacteria chromosome
Describe bacterial transduction
→DNA is transferred from one bacterium to another by a virus
What is bacteria conjugation?
→one bacterium transfers genetic material to another through direct contact
How can gram +ve bacteria be resistant to beta lactams?
→ß-lactamase (Penicillinase)
→Alteration of the transpeptidase enzyme (PBP)
How can gram-ve bacteria be resistant to beta lactams?
→ß -Lactamase (Penicillinase)
→Alteration of porins
What does penicillinase do?
→destroys active part of penicillin molecule
What is augmentin/co-amoxiclav?
→Binds to and inactivates beta-lactamases
→No anti-bacterial activity of its own
Describe beta-lactam resistance in gram -ve
→Porin mutates or new porin type Multi-resistant
→PBP - mutates or bacteria acquires a new PBP
→bacteria acquires a beta-lactamase enzyme
What are the mechanisms by which bacteria become resistant to penicillin?
→Produce penicillinases / beta lactamases that cleave the beta lactam ring- penicillin is inactivated
→Acquire alternative forms of / or mutations in penicillin binding proteins (PBPs) - penicillin can’t bind
→Acquire alternative forms of / mutations in porins - penicillin cannot get into cell
→Acquire alternative forms of / mutations in efflux pumps -penicillins are pumped out faster
How does vancomycin treat MRSA?
→inhibits availability of active site
Describe vancomycin resistance
→Acquisition of van operon by transposition
→Makes D-ala-D-lactate - prevents vancomycin binding
What are the two non-genetic mechanisms of resistance?
→Inaccessibility to drugs, TB lesion
→ Stationary phase/vegetations and biofilms
How can the stationary phase select for resistance?
→non-susceptible to inhibitors of cell wall synthesis
Example of vegetative bacteria
→endocarditis
How to prevent/overcome antibiotic resistance?
→control use
→new or modified drugs
→combination therapy
→infection control
How does combination therapy prevent antibiotic resistance?
→different targets
→overcome mutation rates
How does control use prevent antibiotic resistance?
→not in animal feeds
→complete course [DOTS for TB]
→appropriate prescribing
Example of bacteria which is becoming resistant
→Neisseria gonorrhoeae
What are carbapenems?
→broad spectrum antibiotics
of last resort for Gram negative bacteria
→effective against gram negative
Which type of bacteria is common in the gut?
→gram negative
