Antibiotics

Question 1

What is the principle behind semi-synthetic antimicrobials?

Answer 1

Based on biological compound but modified to make it better i.e.

• change kinetics e.g. Penicillin > methicillin
• reduce toxicity e.g. from methicillin > nafcillin > oxacillin etc.
• modify antimicrobial spectrum e.g. Ampicillin effective against gram -ve bacteria as well as the gram +ve bacteria that Penicillin G and V were effective against

Question 2

What are the principles of empirical “best guess” antimicrobial chemotherapy?

Answer 2

• Is treatment with an antimicrobial needed?
• Is it safe and reasonable to wait before treating?
• Are diagnostic samples needed? (i.e. taking samples before treatment is commenced to effectively identify infection)
• If so, have they been collected?
• What is the likely aetiological agent?
• What is its antimicrobial susceptibility?
• Is there evidence that treatment will benefit the patient?

Question 3

What is the rationale for using antibiotic combinations?

Answer 3

• As a temporary measure in an ill patient - cover a broader spectrum of bacteria e.g. when early signs of septicaemia occur
• To delay the emergence of resistance - start on 4 drugs because they may already be resistant to 2 drugs
• To treat mixed infections
• To reduce toxicity (?)
• To achieve a synergistic effect

Question 4

What are the 3 mechanisms of synergy and what are some examples?

Answer 4

• Block sequential steps of a metabolic pathway - E.g. sulphonamides and trimethoprim block sequential steps in folic acid synthesis (if gets past one block in the pathway, second antibiotic can block it at a later step
• Inhibit enzymatic degradation - E.g. co-amoxyclav inhibits Beta-lactamase degradation
• Enhance antimicrobial uptake by bacterial cell - e.g. aminoglycoside gets in to cell poorly and penicillins interfere with cell wall synthesis so it is easier for aminoglycosides to get in

Question 5

What are the 4 mechanisms of antagonism and what are some examples?

Answer 5

• Inhibition of bactericidal activity by a bacteriostatic agent (e.g., tetracycline + penicillin G in meningitis) i.e. lose bactericidal activity of penicillin and patient outcome is worse
• Induction of enzymatic degradation (e.g. ampicillin + piperacillin)
• Competition for binding to the same target (e.g. lincosamide + macrolide?)

What• Inhibition of target (e.g. polyene + imidazole?)

Question 6

What are Jawetz’s laws

Answer 6

• Bacteriostatic + bacteriostatic = additive or indifferent
• Bacteriostatic + bactericidal = antagonistic
• Bactericidal + bactericidal = synergistic

Question 7

What are the targets of antimicrobial agents?

Answer 7

Question 8

What are the mechanisms of antimicrobial resistance?

Answer 8

• Drug inactivation

By hydrolysis, e.g. β-lactams

By covalent modification, e.g. aminoglycoside, chloramphenicol

• Altering the target of drug action

Modify target to a less sensitive form, e.g. β-lactam, vancomycin

Overproduce target, e.g. vancomycin

• Reduce access of drug to target

Reduced entry into cell, e.g. aminoglycosides

Increase efflux from cell, e.g. aminoglycosides, tetracycline

• Failure to activate inactive precursor of drug e.g. metronidazole, isoniazid

Question 9

How are genes transferred between bacteria?

Answer 9

• Transformation (must have large DNA relatedness)
• Phage-mediated transduction (can occur b/w somewhat unrelated bacteria but still need some relatedness)
• Plasmid-mediated conjugation (can occur b/w entirely different bacteria)

Question 10

How are genes transferred via Transformation?

Answer 10

Question 11

How are bacterial genes transferred via Phage-mediated Transduction?

Answer 11

Question 12

How are bacterial genes transferred via plasmid-mediated conjugation?

Answer 12