Antimicrobials Flashcards
How are antibiotics mostly cleared from the body?
by the bacteria themselves
what is the breakpoint?
the concentration at which bacteria are susceptible to successful treatment by an antibiotic
When is a bacteria classed as resistant in regard to the breakpoint?
if the antibiotic needs to be at a higher concentration than the breakpoint to treat the infection
What classes an infection as multi-drug resistant?
the bacteria are resistant to at least 3 of the major classes of antibiotics
What classes an infection as extensively-drug resistant?
the bacteria are resistant to at least 5 of the major classes of antibiotics
What classes an infection as pan-drug resistant?
the bacteria are resistant to all known classes of antibiotics
What does antibiotic resistance mean in the lab?
when the minimum inhibitory concentration of a drug against a bacteria is greater than the breakpoint
What does antibiotic resistance mean in the patient?
when the minimum inhibitory concentration of a drug against the bacteria is not achieved for long enough to cure the infection
What are four factors that can affect the minimum inhibitory concentration (and therefore the level of antibiotic resistance) in a patient?
dose size/dose frequency, the pharmacokinetics of the drug in the patient, the infection site, the pharmacodynamics of the drugs against the infecting bacteria
What is the definition of antibiotic resistance?
the failure of an antibiotic to kill or arrest a bacterial population
What theory do antibiotics work on?
the lock and key theory
In general, how does antibiotic resistance occur?
resistance methods stop the antibiotic-target site complex developing
What are efflux pumps?
systems in the bacteria that pump out waste products and toxic substances from inside the cell
How are efflux pumps regulated?
DNA
What are the two outcomes of a natural, spontaneous DNA mutation?
they can be silent mutations or have an affect on how the cell functions
What is the consequence of the bacteria developing resistance?
the cell will need to reroute energy from elsewhere
What can happen to bacteria that become resistant to Colistin?
they take longer to grow and divide and can eventually be outcompeted for resources
What is the gene that codes for the metallo-beta-lactamase enzyme?
NDM-1
What does the metallo-beta-lactamase enzyme do?
‘chops up’ beta-lactam antibiotics and renders them inert
Where is the NDM-1 gene carried?
on plasmids
Which class of antibiotics are the most widely prescribed?
beta-lactamase
How can plasmids be spread between bacteria?
conjugation
What is the consequence of the bacteria gaining a plasmid?
it needs to use energy to carry and express those genes meaning the ability of the bacteria to cause infection is significantly impacted
Is a bacteria always a problem if it is highly resistant?
no, if the bacteria cannot spread infection it isn’t clinically relevant
Are antbiotics mostly natural or synthetic?
natural
Which class of antibiotics are entirely chemically synthesized?
quinolones
What are the four mechanisms of antibiotic resistance?
target site modification, replacement of antibiotic target by non-susceptible target, reduced permeability/efflux pumps, enzymatic degradation/modification of the drug
Is reduced permeability/efflux pumps more of a problem in gram +ve or gram -ve bacteria?
gram -ve due to their outer membrane
Are antibiotics lipid or water soluble?
water soluble
What is the normal method antibiotics use to enter a cell?
they hijack a pore
How can bacteria prevent the antibiotics entering the cell?
reducing the size/number of pores
How can you reverse the effect of reduced permeability?
improve the penetration of the antibiotics
How can some bacterial enzymes affect antibiotics?
some actively breakdown the antibiotic, others modify the drug
Can plasmids carry more than one resistance gene?
yes
Does your chance of gaining a resistant strain of bacteria increase or decrease after a course of antibiotics?
increase
How long does it take for your chance of gaining a resistant strain of bacteria go back to baseline after a course of antibiotics?
a year
How does a course of antibiotics make you more susceptible to a resistant strain?
the antibiotics kill bacteria creating a vacuum where another species fill the gap, this species may carry the resistance gene
What are some ways we can combat antibiotic resistance?
smart surfaces, inhibition of resistance, improve failed antibiotics, find new antibiotics, improve existing antibiotics, rapid AMR detection
How can smart surfaces reduce resistance?
a ‘spiky’ silica surface can kill the bacteria before they infect by acting as a physical barrier, this removes the need for antibiotics and reduces the chance of resistance developing
How can inhibition of resistance reduce antibiotic resistance?
blocking the bacterial methods of resistance chemically, by giving another substance in conjunction with the drug such as to block the enzymes that breakdown antibiotics
How can improving failed antibiotics reduce antibiotic resistance?
improve penetration to combat reduced permeability, conjugate the antibiotics with iron molecules that will get taken into the bacteria and bring the antibiotic with it
What is the bacterial iron molecule that you can conjugate with an antibiotic in order to combat reduced permeability
siderophore
What is an antibiotic that you can conjugate with a bacterial iron molecule to combat reduced permeability?
Cefiderocol
How can finding new antibiotics reduce antibiotic resistance?
no common circulating resistance genes yet
What are some ways being used to try and find new antibiotics?
finding the compounds in toad skin or making chemically from fungi
How can improving exisiting antibiotics reduce resistance?
there may be a strain of the current antibiotic that is better at killing bacteria
What are the ways you can try to improve exisiting antibiotics?
modify each gene to see if the end chemical is better at killing bacteria
What is rapid AMR detection?
rapid antimicrobial resistance detection, is a machine that can determine which antibiotics the bacteria are resistant to before you give the treatment to the patient
How can rapid AMR detection reduce antibiotic resistance?
it allows you to determine which antibiotics will actually work and allows the use of effective narrow spectrum antibiotics
