Antibiotics Flashcards
Where are antibiotics derived from and what are their natural functions?
Derived from natural products of fungi and bacteria (soil dwellers) by fermentation then modified chemically
- Natural antagonism and selective advantage
- Kill/inhibit growth of other microorganisms (bacteria)
Some are totally synthetic (e.g. sulphonamides)
When do we use antibiotics?
1) Treatment of bacterial infections
2) Prophylaxis:
- Close contact of transmissible infections
- Prevention of infection (e.g. TB)
- Peri-operative cover for gut surgery
- People with increased susceptibility to infection
What are 8 features that make an antibiotic good?
1) Selective toxicity (harm microorganism, not the host)
2) Good killing activity
3) Slow emergence of resistance (some bacteria have inducible resistance )
4) Narrow spectrum of activity (broad vs narrow in different stages)
5) Non-toxic to host (therapeutic index)
6) Long plasma half-life
7) Oral and parenteral dosing forms
8) No interaction with other drugs (pharmokinetic ADME)
SGSNNLON
Describe the difference between bactericidal or bacteriostatic classified antibiotics?
Bactericidal:
- Kill bacteria
- Used when hosts defense mechanisms are impaired
- Required in serious infections
Bacteriostatic:
- Inhibit bacteria
- Used when the host defense mechanisms are intact
- Used successfully in many infections (not serious)
Some antibiotics can be both (e.g chloramphenicol)
Explain the microbiological principles of therapeutic index
TI = a ratio comparing the blood concentration at which a drug becomes toxic and the ratio at which it is effective
Active dose (MIC) vs toxic effect
The larger the TI, the safer the drug
Ti narrow for toxic drugs
Need to give a dose higher than the MIC (min inhib conc = lowest conc of which a drug prevents growth of visible bacteria)
What are the 5 main target sites of antibiotics mechanism of action?
1) CELL WALL SYNTHESIS
- Beta-lactams (penicillins)
- Glycopeptides
2) PROTEIN SYNTHESIS
- Inhibitors of 30S subunit (Tetracyclines, Aminoglycosides)
- 50S (Chloramphenicol, Macrolides, Oxazolidinones)
3) NUCLEIC ACID SYNTHESIS
- Fluoroquinolones (e.g. ciprofloxacin, levofloxacin) inhibit DNA gyrase
4) METABOLIC PATHWAY
- Sulfonamides and trimethoprim prevent folic acid synthesis (bacteria growth)
5) CELL MEMBRANE FUNCTION
- Polymyxins (e.g. colistin) - increase permability = leakage = inhibits respiration = cell death
CPNMC
Explaing the effect of antibiotics on cell wall synthesis
- Peptidoglycan wall - long sugar polymers, cross-linked by action of enzymes including penicillin-binding proteins (PBPs)
- Beta-lactams (e.g. penicillin) - target PBP, prevent crosslinking (PBP will bind to b lactam ring causing enzyme to be deactivated)
- Glycopeptides (e.g. vancomycin) - bind to D-ala D-ala portion of peptide side chain
- Disruption of peptidoglycan layer = bacterial lysis
Optimising dose of antibiotic
Age, weight, renal and liver function, severity of infection
Susceptibility of organism
Properties of antibiotic
At the site of infection
What are 7 factors to consider when choosing an antibiotic?
1) Distribution in body relative to distribution of bacteria
- some not absorbed from gut
- don’t cross BBB
- do not penetrate abscess
- few accumulate inside cells
2) Toxicity
3) Excretion
4) Patients age
5) Route of administration
6) Type/sensitivity of bacteria
7) COST
What are causes of failure in antibiotic therapy?
DRUG - inappropriate drug, inadequate dose, improper route of administration
HOST - immunocompromised host, poor circulation/ damaged tissue
BACTERIA - natural or acquired resistance, dual infections, dormant, biofilms
LAB - failure to isolate organism or perform appropriate tests
