Introduction To Antibiotics And Resistance Flashcards
Antimicrobial - classification
Antibacterial, antifungal, antiviral & antiprotozoal agents
Antibacterial agents can be classified by there:
– Bactericidal or bacteriostatic
– Spectrum – ‘broad’ v. ‘narrow’
– Target site (mechanism of action)
– Chemical structure (antibacterial class)
How to choose an antibiotic
Is it active against target organism?
Does it reach the site of infection?
Is it available in the right formulation (IV vs oral)?
What is the half life (decides dosing frequency)?
Does it interact with other drugs?
Is there toxicity issues?
Does it require therapeutic drug monitoring? (Too low and it wont do its job, too much and it can cause damage to the body)
Measuring antibiotic activity
Take agar plate and spread bacteria all over the plate evenly
Then place a paper discs containing different antibiotics in the agar plate
The antibiotic will diffuse out in a zonal fashion therefore identifying which one is most effective
Finding the minimum inhibitory concentration (MIC)
Broth microdilation - have test tubes all containing the same known concentration of bacteria
In each one put less and less bacteria until the antibiotics no longer clear all the bacteria
Can see the smallest concentration needed to inhibit the bacteria
Minimum inhibitory concentration (MIC)
Similar to bacteria on paper then agar
Rather than having a circle of paper - you have a strip of paper
But at points on the strip of paper you will have increasing concentration of antibiotic and you can see its effect due to the lack of bacteria growing nearby
Classes of antibacterials and their mechanisms of action
Act on cell wall synthesis - i.e. stop cell wall from forming so bacteria cell dies as they cant repair cell walls, so any damage to it, is kept, therefore water comes in and it dies e.g. Beta-lactams
Some prevent cell membrane function - e.g. polymixins
Some prevent nucleic acid synthesis - e.g. tetracyclines, aminoglycosides
Some prevent protein synthesis - Quinolones, rifampicin
Penicillin targets penicillin binding proteins which prevents the cell wall from forming - therfore cell wall doesn’t form properly and the bacteria is more sensitive to breakdown/death
Same for vancomycin
Types and mechanisms of resistance
Types of resistance
Intrinsic – No target or access for the drug – Usually permanent - drug would never have worked in the first place so there would be no need to run tests on it
Acquired – acquires new genetic material or mutates – Usually permanent - (natural pathway of evolution)
Adaptive – The organism responds to a stress (e.g. subinhibitory level of antibiotic presence)
Mechanisms of resistance - Enzymatic modification or destruction of antibiotics - enzymes present in bacteria are able to destroy/ modify the antibiotics therefore not killed off by them
Enzymatic alteration of antibiotic targets - bacteria is able to “change” the antibiotic target site therefore antibiotic cant inhibit/stimulate it’s required target therfore unaffected
Mutations of bacterial target sites so antibiotics dont work
Mechanisms of chromosomal gene mutation
One bacteria has the mutation that makes it resistant to the antibiotic
Antibiotics is introduced and kills all cells apart from bacteria with mutation
Antibiotic resistant bacteria then goes on and divides so all daughter cells have this resistance - rendering the antibiotic less affective/potentially useless than before
Horizontal gene transfer
Bacteria undergo this all the time, i.e. this is how the organism transfers genetic material from bacteria to bacteria
When transferring/ replicating the F plasmid, if it contains information that encodes for anti bacteria resistance then different strains of bacteria can gain this resistance, therefore decreasing the effectivness of bacteria - even in strains it hasn’t been “tried” out in
Beta-lactams
Largest group of antibiotics Contains - penicillins Cephalosporins Carbapenems
Penicillins
Penicillin – Mainly active against streptococci
Amoxicillin – Also some activity against Gram-negatives
Flucloxacillin – Active against staphylococci & streptococci
Beta
Cephalosporins
Generations’ with
Carbapenems
Carbapenems such as meropenem, ertapenem, imipenem -
Very broad spectrum (incl anaerobes)
Active against most (not all) Gram negs
Generally safe in penicillin allergy
Often considered the ‘reserve’ antibiotic for Gram-negative infections.
glycopeptides
Vancomycin
– Active against most Gram pos (not Gnegs)
– Some enterococci are resistant (VRE)
– Resistance in staphs rare
– Not absorbed (oral for C. difficile only)
– Therapeutic drug monitoring (TDM) required (narrow therapeutic window)
Teicoplanin
– Similar activity to vancomycin
– Easier to administer
Tetracycline and doxycycline
Similar spectrum, both oral only
Broad-spectrum but specific use in penicillin allergy, usually for Gram pos
Active in atypical pathogens in pneumonia
Active against chlamydia & some protozoa
Shouldn’t be given to children <12 years, pregnant and breastfeeding women (causes staining of developing teeth).
