Lecture 4 - Antibiotics Flashcards
what does antibiotic mean?
anti = against
biotic = life
what is the definition of an antibiotic?
a substance produced by a microorganism that is effective in inhibiting the growth of other microorganisms
what is an antimicrobial agent?
a synthetic drug used to treat an infectious disease
what are the types of antimicrobial agents?
- antibacterial
- antifungal
- antiprotozoal
- antiviral
what does it mean if the origin of an antibiotic is organic?
it was isolated from bacteria or fungi
- penicillin
what does it mean if the origin of an antibiotic is semi-synthetic?
there was further derivatisation of the organic compound for greater efficacy
- amoxicillin, methicillin
what does it mean if the origin of an antibiotic is synthetic?
generated in the lab
- sulfonamides
what is the antibacterial spectrum?
An antibiotics range of activity against bacteria, e.g broad spectrum and narrow spectrum?
what does it mean if an antibiotic is narrow spectrum?
it only works against a limited variety of bacteria
- vancomycin only works against gram +ve
what is bacteriostatic activity?
level of antimicrobial activity that inhibits growth of an organism but doesnt kill it
what is bactericidal activity?
a level of antimicrobial activity that kills the organism
what is antibiotic combination?
combining antibiotics to:
- broaden antimicrobial spectrum
- treatment of polymicrobial infections
- prevent emergence of resistant organism
- achieve a synergistic effect
what is antibiotic antagonism?
activity of one antibiotic interferes with the activity of another (so the sum of the two ABs is less effective than the most active individual drug)
what is antibiotic synergism?
antimicrobial activity is higher than the sum of combined drugs
what are the three main ways to perform an antibiogram?
- semi-quantative based of diffusion (kirby-bauer method)
- Quantative based on dilution series
- determining the minimum bacterial concentration (MBC)
what is the kirby-bauer method?
spots of AB on an agar plate. effectiveness of AB is dictated by the diameter of the clear zones
what is the ‘quantitive based on dilution’ series’?
the lowest concentration of antibiotic in which no growth is occurring but the bacteria isnt killed. (MIC)
what measure does the dilution series test for?
minimum inhibitory concentration (MIC)
what is MBC?
minimum bacteriocidal concentration - the minimum concentration required to kill a bacteria strain
- reduction of colony forming units (CFU) to 99.9% below control
how can we test for the minimum bacteriocidal concentration?
by subculturing the clear broth onto an antibiotic-free solid media
which drugs block bacterial cell wall synthesis?
1: beta-lactam ABs (penicillin)
2: Glycopeptides (vancomycin)
what are the three main beta-lactam ABs?
- penicillin
- cephalosporins
- carbapenems
how do beta-lactam antibiotics block bacterial cell wall synthesis?
they inhibit peptidoglycan synthesis by binding transpeptidase, a penicillin binding protein.
this prevents cross-linking of peptide chains in the cell wall.
- this causes a weak cell wall and results in osmotic lysis of the bacterium
what kind of bacteria are resistant to penicillin?
gram negative, because it cannot penetrate the outer membrane porins
what can we do to allow penicillin to pass the gram negative outer membrane?
use an extended spectrum penicillin such as amoxicillin and ampicillin, which are semi-synthetic
how do glycopeptides inhibit cell wall synthesis?
they block cell wall synthesis by binding to peptidoglycan subunits, preventing proper assembly and cross-linking
- causes weak cell wall and osmotic lysis
is penicillin bacteriocidal?
yes, its action kill the bacteria
what is the most popular glycopeptide antibiotic?
Vancomycin
why is vancomycin the drug of last resort?
because it is often used to treat drug resistant bacterial infections, such as methicillin resistant staphylococcus aureus. its use is limited due to concerns about resistance and potential side effects
which drugs act as inhibitors of RNA transcription of bacteria?
rifamycins
which drugs act as inhibitors of nucleic acid synthesis?
quinolones and fluroquinolones (synthetic)
how do quinolones and fluroquinolones work?
they bind DNA topoisomerases (e.g helicase) and prevent DNA replication, ultimately leading to cell death, and so are bacteriocidal
are rifamycins bacteriocidal?
yes
what are antimetabolites?
antibiotics that interfere with metabolic processes by mimicking substrates
what are the two main classes of antimetabolites?
sulfonamides and trimethoprim
what are the common features of sulfonamides and trimethoprim?
- they are bacteriostatic, so prevent growth but do not kill
- they both block the pathway of tetrahydrofolic acid synthesis
- commonly used against UTIs
which drugs act to inhibit protein synthesis by binding to the 30S subunit? (bacterial ribosomal subunit)
aminoglycosides and tetracyclines
how do aminoglycosides work?
- freeze the 30S initiation complex, which causes misreading of DNA due to frame shifts
what are the features of aminoglycosides
- most effective against aerobic (respiration), gram negative bacterium
- bacteriocidic
- synergistic with penicillins
what are the three most common aminoglycosides?
- neomycin
- gentamycin
- kanamycin
how do tetracyclines work?
they inhibit the binding of aminoacyl-t-RNA to the acceptor site on the ribosome
what are the features of tetracyclines?
- they are broad spectrum and are used against many bacterial infections
- they are bacteriostatic
what are the two most common tetracyclines?
- tetracycline
- doxycylcine
which drugs act to inhibit protein synthesis by binding to the 50S subunit? (bacterial ribosomal subunit)
- macrolides (erythromycin)
- chloramphenicol
what are the features of macrolides
- most effective against gram positives and mycoplasma
- is bacteriostatic
how do macrolides work?
bind to 50S subunit and inhibit translocation of the peptidyl tRNA from the A to the P site
what is the most common macrolide?
erythromycin
how do rifamycins work and what are they typically used against?
they inhibit bacterial RNA polymerase, and are typically used against mycobacteria
what is the most common rifamycin?
Rifampin
what are the common features of quinolones and fluoroquinolones?
- they are broad spectrum
- bacteriocidal
- commonly used against UTIs
what is the most common quinolone and the most common fluroquinolone?
Q = Nalidixic acid
FQ = Ciprofloxacin
what do sulfonamides inhibit?
they are an antimetabolite that competitively inhibits pteridine synthase
what does trimethoprim inhibit
bacterial dihydrofolate reductase
what are the common features of chloramphenicol
- used mostly in topical applications such as eye drops
- broad spectrum
- bacteriostatic
what are the two types of antibiotic resistance?
- non-genetic/intrinsic drug resistance
- genetic resistance
what are the three types of intrinsic drug resistance?
- metabolic inactivity.
- drugs wont work on metabollically dormant cells - lack of target structure
- mycoplasmas lack a cell wall - Exclusion
- antibiotic cant enter cell, like penicillin can’t enter gram negative
what are the two types of genetic resistance?
- chromosomal resistance
- spontaneous mutation in a gene encoding a target receptor (mutation of RNA-polymerase gene results in a rifamycin resistance) - acquired resistance
-bacteria gain resistance genes through horizontal gene transfer of plasmid DNA
how does selective pressure work for bacteria adapting to antibiotics?
before selection, there are a variety of resistance levels of bacterium
directly after selection, only the high resistance bacteria survived
so now only high resistance bacteria grow and remain
- survival of the fittest
list the 6 antibiotic resistance mechanisms
- exclusion of AB from the site of action (AB can’t enter through porins)
- Efflux pump for the antibiotic -> removal from the site of action
- enzymatic modification of AB
- Destruction of AB
- Modified AB insensitive target
- New antibiotic insensitive target
what does beta lactamase do
destroys penicillin by hydrolysing the beta lactam ring between the carboxyl and nitrogen.
what are two types of beta lactamases
- penicillinase
- cephalosporinase
what is bad about beta lactamase in terms of resistance?
b-lactamases are plasmid encoded enzymes that can be transferred between bacterial strains and species via horizontal gene transfer, increasing AB resistance
which penicillin derivatives are unaffected by beta lactamase?
- methicillin
- oxacillin
- flucloxacillin
what is a beta lactamase inhibitor?
clavulanic acid
how can we use amoxicillin and have it be effective even though beta lactamase breaks it down?
by combining it with clavulanic acid to get augmentin
what is the most known example of bacteria that develop resistance against b-lactamase resistance penicillins?
MRSA -> methicillin resistant staphylococcus aureus.
how is MRSA resistant to even beta lactamase resistant penicillins?
MRSA bacterium create a new penicillin binding protein PBP, which does the same job as the original transpeptidase, but has a low affinity for beta lactams
what is staphylococcal cassette chromosome mec? (SCCmec)
the SCCmec is a mobile component of bacterial chromosomes (chromosomal cassette, not a part of plasmid DNA) that contains the MecA gene, which codes for Penicillin Binding Protein 2a.
what is community acquired SCCmecIV vs hospital acquired SCCmecII
spreads in different places (community vs hospitals
hospital acquired is harder to treat and highly resistant, whereas community acquired isnt resistant to non-beta lactam ABs and is easier to treat
what are multidrug resistant strains?
strains that are resistant to more than one class of drugs
what are pandrug-resistant strains?
strains that are resistant to all clinically safe drugs
