antibiotics Flashcards
likely causative organsims for otitis media and sinusitis
strep pneumoniae, H. influenzae - amoxycillin
two mechanisms of drug inactivation causing resistance to antimicrobial agents
- hydrolysis - eg. pseudomonas aeroginosa produces beta-lactamase - hydrolysing beta-lactam antibiotics - covalent modification - eg. modification of aminoglycosides
2 ways to create resistance in bacteria
intrinisic acquired (mutation or horizontal gene transfer)
antimicrobial agents that act on cell wall
beta lactams, glycopeptides
how are the MIC and the zone of antibiotic clearance diameter related?
the bigger the zone diameter the lower the MIC
tobramycin active against
pseudomonas aeroginosa
examples of altering the target of drug action by micro-organsims
- modify target to less sensitive form - B-lactam (altered PBP), and vancomycin (sugar instead of D-ala)
flucloxacillin used to treat which type of bacteria
staphyloccus - low toxicity
what is the synergistic effect when combining 2 antibiotics together?
when you add the 2 drugs together you get an unexpected positive benefit
How does the E-test strip work?
another type of diffusion test - log scale of two fold dilution on a piece of filter paper
what is the antagonistic effect when combining 2 antibiotics together?
the two drugs interfere with each other - get a worse outcome compared with either of them by themselves
examples of reducing access of drug to target by micro-organisms
-reduced entry into cell - aminoglycosides -increased efflux from cell - aminoglycosides, tetracycline
how does the disc susceptibility test work?
discs of antibiotics placed into a culture of micro-organism - see if there are rings of no growth
what is the mechanism of the synergistic effect of antibiotic combinations?
- they block sequential steps of a metabolic pathway - inhibit enzymatic degredation - enhance antimicrobial uptake by bacterial cells
3 types of horizontal transfer
transformation phage mediate transduction plasmid-mediated conjugation
what is the indifferent effect when combining 2 antibiotics together?
on their own the antibiotics have an effect when adding them together - they have a better effect, however this could have just been achieved by increasing the concentration of one of the antibiotics
how are antimicrobial agents classified?
source: natural or synthetic broad mechanism of action
how is aminoglcoside resistance achieved
- modified outer membrane causing reduced entry 2. enzymatic modification causing reduced entry (acetylation, adenylation, phosphorylation, adenylation phosphorylation) 3. ribosomal mutation - reduces binding
antimicrobial agents that act on cytoplasmic membrane
polymyxins, polyenes
why to transpeptidases bind to beta-lactams?
recognise the beta-lactam ring as similar to the bond between terminal D-ala amino acids
how is beta-lactam resistance achieved?
1) beta lactamases - acts on beta-lactam ring and hydrolyses it 2) altered PBP - makes something beta-lactams will bind to but does not interfere with cross linking
how do you determine the MIC using the E test
where the clear zone edge intersects this piece of paper = MIC
What is the micro-organism that changes the terminal D-ala so vancomycin cant bind?
enterococci
why are semi-synthetic drugs useful?
you can alter the pharmacological properties of antibiotics to suit use - change kinetics - reduce toxicity - modify antimicrobial spectrum
what are the 2 effects anti-microbial agents can have
bacteriostatic bactericidal
how can vancomyin resistance be achieved
bacterium replaces the terminal D-ala with a sugar and so vancomycin cant bind strongly
carbenicillin important for which organism?
pseudomonas aeruginosa
what is the micro-organism that overproduces the peptidoglycan wall so vancoymycin cant bind?
staphlococcus aureus
methicillin used to treat which type of bacteria
staphyloccus - moderate toxicity (nephrotoxic)
how is peptidoglycan cross-linking achieved
transpeptidase enzymes catalyse the cross linking by removing the terminal D-ala from the precursor peptidoglycan
what is plasmid-mediated conjugation
formation of sex pillus (cytoplasmic bridge) replication and transfer of DNA plasmid across bridge and recombination
metranidozole only acts on…
strict anaerobes
examples of drug inactivation by micro-organisms
hydrolysis - B-lactams covalent modification - aminoglycoside
difference between penicillin G and penicillin V
penicillin G was destroyed in the stomach as so had to be given by injection penicillin V acid stable - able to be taken orally
gentomycin active against
lots of gram -ve bacteria
what are the mechanisms for antagonism
- inhibition of the bactericidal activity by a bacteriostatic agent - induction of enzymatic degredation - competition for binding to the same target - inhibition of target
likely causative organsims for UTI, cystitis
>80% E coli - cephalexin or co-amoxyclav or trimethoprim
bonus of using ampicillin compared to penicillin G
ampicillin can also treat gram negative rods (penicillin G could not)
MRSA - resistant to which antibiotics
all beta-lactam antibiotics
2 mechanisms of altering target of drug action to cause resistance to antimicrobial agents
- modify target to a less sensitive form - eg. MRSA - altered PBP for beta-lactam. eg. VRSA - put sugar instead of D-ala at end of peptidoglycan precursor 2. overproduction of target - eg. overproduce peptidoglycan in staph aureas- soaks up vancomycin
what is transformation
donor bacterium lysis - fragments of DNA DNA uptake by competent cells homologous recombination4 (must be between closely related bacteria)
antimicrobial agents that act on folic acid
sulphonamides, trimethoprim
likely causative organsims for a sore throat and the antibiotic of choice
>50% viral - no antibiotic strep pyogenes - penicillin
examples of failure to inactivate inactive precursor of drug
metronidazole isoniazid
targets for antimicrobial agents
cell wall - beta lactams, glycopeptides cytoplasmic membrane - polymyxins, polyenes ribosomes - aminoglycosides, chloramphenicol nucleic acid - rifamycins, quinolones folic acid - sulphonamides, trimethoprim
what are the types of anti-microbial agents
antibiotics - naturally occurring chemotherapeutic agents - synthetic semi-synthetic
action of aminoglycosides
bind to 30s ribosome of bacterium - distorts the reading frame for transcription –> introduces abnormal amino acid or stops transcription completely
likely causative organsims for skin infection
staph aureus or strep pyogenes - penicillin, mupirocin, dicloxacillin
action of ticarcillin
resistant to chromosmal encoded beta-lactamse
antimicrobial agents that act on ribosomes
aminoglycosides, chloramphenicol
what does phage mediated transduction have the potential to do to cause a epidemic pathogen?
could transfer R between staph epidermis and staph aureas
2 mechanisms to reduce access of drug to target to cause resistance to antimicrobial agents
- decrease entry into cells - eg. R to aminoglycosides 2. increased efflux from cell - eg. aminoglycosides, tetracyline
action of beta-lactam antibiotics
binds to transpeptidases directly -> suicide inhibition -> stops the formation of cross linking of peptidoglycans for cell wall
How does the dilution method work for antibiotic susceptibility testing?
series of test tubes with different concentration of antibiotics - do a two fold dilution across the tubes with growth medium in it. Then add micro-organism and incubate overnight. Look for the lowest conc that inhibits the growth of the organism
action of clavulonic acid
resistant to plasmid encoded but not chromosmal encoded beta-lactamse
basic structure of beta-lactam antibiotics
5 carbon chain ring with 4 carbon chain ring. Joined together by a N and with a double bonded oxygen to the 4 C ring. They differ in the substitution in the 5 C ring and whether they have a single or double bond in the 5 C ring
two main methods for antibiotic susceptibility testing
dilution methods diffusion methods
How do you determine the MIC?
the lowest antibiotic concentration that prevents micro-organism growth (first clear tube)
antimicrobial agents that act on nucleic acid
rifamycins, quinolones
what are the 3 types of effects you can get when combining 2 antibiotics
indifference antagonism synergy
Action of vancomycin
binds to terminal D-ala of peptidoglycan precursor stopping the action of transpeptidase
example of failure to activate inactivate precursor of drug to cause resistance to antimicrobial agents
metronidazole - only activated in strict anaerobic bacteria some myco TB dont have the Kat enzyme to convert it to its active form and therefore are Resistant
what kind of bacteria can vancomycin act on
only acts on gram positive bacteria (cannot pass through outer lipid membrane of gram negative bacteria)
what is phage mediated transduction?
infection of recipient cell with abnormal phage with R genes encoded –> recombination into chromosome
what does transformation have the potential to do to cause a epidemic pathogen
transfer antibiotic R from commensals to pathogens
likely causative organsims for an acute exacerbation of chronic bronchitis
H. influenzae or strep pneumoniae - treat with amoxycillin or doxycyciline
