Lecture 15 - Antimicrobial mechanisms and Resistance Flashcards
Difference between antibiotics and chemotherapeutic agents
Antibiotics are naturally-occurring
Chemotherapeutic agents are synthetic
Goal of semi-synthetic drugs
1)
2)
3)
1) Alter kinetics
2) Reduce toxicity
3) Broaden antimicrobial spectrum
When might it be useful for a drug to have a short half life?
If excreted by the kidneys, for a UTI
Increases the amount of antimicrobial in the urinary tract
Which type of bacterium is Bordatella?
Gram - rod
Bordatella intrinsic resistance
Intrinsically resistant to penicillin
Phases of bacterial growth curve
1)
2)
3)
1) Lag phase
2) Exponential phase
3) Stationary phase
What qualifies an antimicrobial as bactericidal?
Kills 99.9% of bacteria
3-log reduction (log10 scale)
When are bactericidal antimicrobials necessary?
In immunocompromised patients
Tetracycline structure
Four hexagonal carbon rings
Structural difference between penicillin and cephalosporin beta-lactams
Penicillin is a beta-lactam ring attached to a pentagonal structure
Cephalosporins are beta lactam ring attached to a hexagonal structure
Tetracycline pharmacokinetics
Very short half-life
Excreted in bile
How are tetracyclines excreted?
In bile
Penicillin examples 1) 2) 3) 4) 5) 6)
1) Penicillin G
2) Penicillin V
3) Ampicillin
4) Methicillin
5) Flucloxacillin
6) Carbenecillin
Penicillin G oral availability
Low
Penicillin V oral availability
Good
Organisms susceptible to penicillin G
Gram + rods, cocci
Gram - cocci
Organisms susceptible to penicillin V
Gram +rods, cocci
Gram - cocci
Toxicity of penicillin G and V
Very low
Organisms susceptible to ampicillin
Gram + rods, cocci
Gram - rods, cocci
Ampicillin oral availability
Good
Ampicillin toxicity
Very low
Methicillin toxicity
Moderate
Organisms susceptible to methicillin
Gram + cocci
Targeted against staphylococci
Methicillin oral efficacy
Poor
Organisms susceptible to flucloxacillin
Gram + cocci
Targeted against staphylococci
Flucloxacillin toxicity
Low
Flucloxacillin oral availability
Good
Carbenecillin oral availability
Poor
Organisms susceptible to carbenecillin
Gram - rods
Targeted against pseudomonas
Antimicrobials used particularly against gram + cocci, EG: staphylococcus
Methicillin, flucloxacillin
Antimicrobial particularly used against G- rods, EG: pseudomonas
Carbenicillin
Carbenecillin toxicity
Very low
Antimicrobials targeting cell wall
1)
2)
1) Beta lactams
2) Glycopeptides
Antimicrobials targeting cytoplasmic membrane
1)
2)
1) Polymixins (antibacterial)
2) Polyenes (antifungal)
Antimicrobials targeting ribosomes
1)
2)
1) Aminoglycosides
2) Chloramphenicol
Antimicrobials targeting nucleic acids
1)
2)
1) Rifamycins
2) Quinolone
Antimicrobials targeting folic acid synthesis
1)
2)
1) Sulphonamides
2) Trimethoprim
Bacteria innately resistant to sulphanomides
Enterococci
Can’t synthesise folate
Can humans synthesise folate?
No
Examples of bacteria to be treated with ampicillin
Salmonella
Haemophilus influenzae
Which antimicrobial would salmonella and H. influenzae be treated with?
Ampicillin
