Lecture 20 - Antimicrobial Drug Resistance Flashcards
When was the first case of penicillin resistant S aureus?
1947
When was the first case of MRSA in the UK?
1960
What are the two types of resistance?
intrinsic and acquired
What is intrinsic resistance?
if we give a antibiotic used for gram positives to treat gram negatives
e.g. gram negatives are intrinsically resistant to vancomycin
How is acquired resistance acquired?
either by vertical or horizontal transfer
What is vertical transfer?
if a mother cell is in the presence of a drug, it is possible that some spontaneous mutations occur leading to this sensitive cell producing some drug resistance
What can drug resistant bacteria do?
survive and multiply and form many colonies of bacterial cells carrying DNA that will code for drug resistance
What are the steps of vertical transfer?
non resistant bacteria exist
bacteria multiply by the millions
some mutations make the bacterium drug resistant, in the present of drugs only the resistant bacteria survive
drug resistant bacteria multiply and thrive
What are the types of horizontal transfer?
transformation
conjugation
transduction
What is transformation?
if a drug resistant cell is killed by another antibiotic, the bit of the plasmic with genes conferring drug resistance can be transferred to another cell
bacterial cell transferring info to another bacterial cell
What is conjugation?
when bacteria are in close proximity and can transfer genes coding for drug resistance from a resistant bacterial cell by producing a bridge/link between the two cells
What is transduction?
happens when a bacterium becomes infected with a virus
viruses replicate inside the bacterial cell and if they do this within a drug resistant bacteria then once they leave they take some DNA coding for drug resistance
they continue to reinfect sensitive bacterial cells and bring these bits of info coding for resistant into these cells
What are bacterialphages?
viruses that infect bacteria
Examples of antimicrobial resistance?
reducing drug accumulation
inactivating/altering drugs
altering target sites
Reducing drug accumulation?
production of efflux pumps which remove any antibiotics that enter the cell
changes the structure of the porins
What does changing the structure of the porins do?
they no longer act as a way for small hydrophilic drug molecules to get into the gram negative - stops the drug working
Inactivating/altering drugs?
beta lactamases
degrade beta lactam antibiotics
What can the resistance genes of beta lactamases code for?
new penicillin binding proteins that work in the presence of beta lactams
Altering target sites?
changes in ribosomes (macrolides)
changes in PBPs (MRSA)
What is there correlation between with AMR?
antimicrobial resistance/overuse and high levels of AMR
What do resistant microbes do?
increase the severity and duration of an illness (high costs)
Why is rapid emergence of AMR a problem?
ease of transfer between species
bacteria multiply very rapidly and are able to transfer the genes coding for drug resistance very easily
What is a reason AMR is such a problem?
dramatic decline in antibiotic research and discovery
What are the ESKAPE pathogens?
Enterococcus faecium
S. aureus
Klebsiella (-ve)
Acinetobacter (-ve)
Ps. aeruginosa (-ve)
Enterobacter
Why are the ESKAPE pathogens a problem?
they have developed ways to resist most of the current drugs available
need to find alternative ways to treat these
What are beta lactamases?
bacterial enzymes that degrade beta lactam antibiotics
What was penicillinase produced by?
first penicillin-resistance S. aureus
What % of S. aureus are resistant to benzylpenicillin?
> 90%
What was developed in response to resistance?
meticillin (no longer used by gave flucloxacillin)
temocillin
Why is flucloxacillin beta lactamase resistant?
it has a bulky side chain which acts as a protective shield to protect the carbon on the beta lactam ring from being attacked by beta lactamases
Why is temocillin resistant to beta lactamases?
has an additional O methyl substituent which stops the beta lactamases attacking the neighbouring carbonyl
Co-amoxiclav?
amoxicillin + clavulanic acid
Tazocin?
piperacillin + tazobactam
What are beta lactamase inhibitors?
clavulanic acid and tazobactam
What were meticillin type drugs developed for?
to resist beta lactamase attack
What did MRSA do?
meticillin resistant staph aureus
found a way to produce new PBP that are not inhibited by flucloxacillin
What is the one treatment choice for MRSA?
vancomycin
What is VRSA?
there are now some vancomycin resistant staph aureus so there needs to be new treatments developed
What do extended spectrum beta lactamases degrade?
penicillins (except temocillin)
cephalosporins
monobactams
What do metallo-beta-lactamases (NDM 1) degrade?
penicillins
cephalosporins
carbapenems
What do metallo-beta lactamase (KPC) degrade?
penicillins
cephalosporins
monobactams
carbapenims
What are some metallo beta lactamases?
not inhibited by clavulanic acid nor tazobactam
How to tackle AMR?
use antibiotics in the right way
dont keep/share antibiotics
never use antibiotics for viral sore throats
select most appropriate antibiotic
reserve highly effective antibiotics for severe infections
provide advice
develop local antimicrobial guidelines
prevent transmission
develop quicker diagnostics
support drug discovery
develop education/training
raise awareness
