Antiobiotics and Antimicrobial Reseistnace Flashcards
whats the difference between antibiotics and antimicrobials?
- *antibiotics:** natural antimicrobial substance - produced by living organism
- *antimicrobial:** any substance that kills or inhibits growth of microbes
all antibiotics are antimicrobials, but not all antimicrobrials are antibiotics
what is selective toxicity?
what can you target to achieve this?
selective toxicity: drug that kills or inhabits growth of pathogen without harming the host
- *target:**
- different essential vitamins that bacterial use
- bacterial cell wall
- bacteria rb (50S & 30S)
- bacterial mt
- DNA and RNA synthesis different
which are the current exploited antibiotic targets?
what are the most successful?
- inhibition of bacterial cell wall synthesis
- inhibition of bacterial protein synthesis
- inhibition of DNA transcription and replication
- inhibition of RNA synthesis and replication
- *most successful hit:**
- rb
- cell wall synthesis
- DNA gyrase or DNA toposiomerase
what are the classification of antibacterial agents? (2)
spectrum activity: broad spectrum: (target all) OR narrow spectrum: (e.g. only target gram positive or gram negative / or gram positive aerobes)
mode of action: bacteriostatic (stops it growing) or bactericidal (kils). in clinic can be both - depending on dose, duration of exposure or the state of invading bacteria
bacteriostatic or bactericidal e.g.s?
awareness probs
which drugs target bacterial cell walls? how work?
explain how pencillin works
explain how glycopeptide antibiotics work
explain how polymyxins work
beta-lactam antiobiotics: inhibit cell wall synthesis
work: inhibit step in synthesis of peptidoglycan (most contain a B-lactam ring). causes cells to osmotically lyse
pencillin:
bacterial cell wall grows: get cross links between cell wall by pentaglycine (using enyzme transpeptidase)
penecillin acts as a mimic: as a substrate for transpeptidase. blocks it working
glycopeptide antibiotics:
- too big to get through cell wall
- block D-ala residues (D-ala form the cell wall cross links) from forming cross links by forming H-bonds between the D-ala
- used on gram-positive bacteria
polymyxins:
- bind to charge structures of cell walls on gram negative bacteria
- changes the charge
- this destabilises cell wall
- rupture
how do antibacterial targeting protein synthesis work?
what do aminglycosides, tetracylines, macrolides and chloramphenicol do?
- aminglycosides: change shape of 30S portion & disrupt the structure (Gentamicin, tobramycin and amikacin). Gram-negative bacteria. can cause hearing loss and renal impairment. IV drugs
- tetracyclines: bind to 30S. interfere with attachment of tRNA to rb. oral drugs
- macrolides: bind to 50s subunit. prevents translocation
- chloramphenicol: bind to 50S, inhibit formation of peptide bond
which drugs act on nucelic acid synthesis?
quinolones / fluoroquinolones:
- broad spectrum
- bind to topoisomerase II (DNA gyrase) and topoisomerase IV and inhibit DNA synthesis.
Rifampicin:
- acts on RNA transcription: inhibits RNA polymerase on gram postive
- treats TB
which drugs target bacterial metabolic pathways
drugs target metabolic pathways unique to bacteria
- *e.g. Sulphonamides and folic acid inhbitors: (e.g. trimethoprim and sulfamethoxazole)**
- competitive inhibitors of bacterial synthesis of folic acid: block the bacterial precursor of FA - PABA by binding themselves, so FA cant be produced
how do inactivated bacterial vaccines work?
what are the two types and what subtpyes?
- *inactivated vaccines:**
- chemical treatment of part of bacteria to make inactive: e.g. heat or purifcation of protein
- large amount of antigen produces antibody repsonse
- *inactiaved bacterial vaccines:
- **whole bacteria killed
- protein subunits inactivated
- toxoid inactivated
- *polysaccharide vaccines** (usually from cell wall):
- pure poly.
- conjugate vaccines
how do live bacterial vaccines work?
- live attenuated (weakened) bacteria are grown over period of time
- e.g. cholera
- attenuated live bacteria will multiply more slowly than virulent strains
what is antimicrobial susceptibility testing? why do it?
= the measurement of the susceptibility of bacteria to antibiotics.
- to see whether the therapy is likely to be effective
- enable narow therapy to reduce AEs
- allows data on resistance
- enable antimicrob policies to be formed
- provide surveillance
what is minimal inhibitory concentration (MIC) of antiobiotic?
= minimal concentration of antibiotic required to inhbit the growth of organism
e.g. in picture: MIC = 0.03 mg/l
what are two methods of antimicrobial sus. testing?
broth microtitre dilution: often determined in 96-well microtiter plate format, bacteria are inoculated into a liquid growth medium in the presence of different concentrations of an antimicrobial agent. Growth is assessed after incubation for a defined period of time (16-20 h) and the MIC value is read. uses spectrophotometry
disc diffusion tests :An effective antibiotic will produce a large zone of inhibition (disk C), while an ineffective antibiotic may not affect bacterial growth at all (disk A).
what does susceptibility, intermediate and resistant mean?
what is a breakpoint??
susceptibility: bacterial strain inhibited in-vitro by a conc of an antimicrobial agent that is associated with a high likelihood of therapeutic success
intermediate: bacterial strain inhibited in-vitro by a conc of an antimicrobial agent that is associated with a uncertain therapeutic success
resistant: bacterial strain inhibited in-vitro by a conc of an antimicrobial agent that is associated with a high likelihood of therapeutic failure
breakpoint concentration: A breakpoint is a chosen concentration (mg/L) of an antibiotic which defines whether a species of bacteria is susceptible or resistant to the antibiotic. changes all the time
what do u do after done antimicrobial sus testing?
use a EUCAST Breakpoint tables: interpret test to indicate if microbe is susceptible or resistant
what are PD indecies for antimicrobial activity and MIC?
effect of drug regarding its antimicrobial activity can differ regarding PD indices:
- Cmax / MIC ratio - concentration depending killing: most importnat is getting high conc above MIC.
- T>MIC - time dependent killing - most important is time above MIC. with minimal prolonged antibiotic effect
- *- AUC24 / MIC ratio** - combo of above time dependent killing with prolonged antibiotic effect
