Infection 7 - Antibiotics + Resistance

Question 1

In what 4 ways can antibiotics be classified?

Answer 1

1) Bactericidal or Bacteriostatic
2) Spectrum - broad or narrow
3) Target site - e.g.: cell wall, DNA synthesis etc.
4) Chemical structure - e.g.: B-lactams

Question 2

What are two methods of measuring antibiotic activity?

Answer 2

1) Disc-sensitivity testing - put antibiotic disc in bacterial culture and measure zone of clearance. Compare against break point values.
2) Minimum Inhibitory Concentration (MIC) - Increase concentration of AB’s within broth micro-dilution and find minimum concentration at where there is no bacterial growth (broth is clear).

Question 3

Describe the 3 main types of antimicrobial resistance

Answer 3

1) Intrinsic - natural resistance to an AB without need for mutation. Either no target present for drug or unable to gain access to target, therefore usually permanent. E.g.: Gram-negative have intrinsic resistance to AB’s targeting peptidoglycan due to outer membrane.
2) Acquired - gene mutations or transfer allow resistance to a previously susceptible AB. E.g.: production of enzymes, alteration of target site, over-expression of efflux pumps etc.
3) Adaptive - organism responds to mild-stress (sub-inhibitory level of AB), switch on genes which confer resistance.

Question 4

Describe 3 mechanism of AB resistance

Answer 4

1) - Enzyme modification or destruction of ABs’ - e.g.: B-lactamases produced by S. aureus.

2) Enzymatic alteration of targets
3) Over-expression of efflux pumps

Question 5

What are the 2 ways in which bacteria can confer resistance?

Answer 5

1) One bacteria carrying resistance mutation reproduce in large numbers of resistant bacteria
2) Horizontal gene transfer - transfer of resistant gene on plasmid via pillus to donor cell.

Question 6

What is the MOA for B-lactam antibiotics?

Answer 6

• Bind to PBP’s on bacteria
• Inhibit transpeptidation enzyme (responsible for linking peptidoglycan chains)
• Therefore, disrupt bacterial cell wall synthesis (bactericidal)

Question 7

What are the 3 main subgroups of B-lactams, give examples and what they are used to treat.

Answer 7

1) Penicillins - e.g.: amoxicillin - have a wide range of clinical applications e.g.: bone + joint infections, skin infections, UTI’s + STI’s
2) Cephalosporins - e.g.: ceftriaxone - used for pneumonia, meningitis, UTI’s, biliary tract infections
3) Carbapenems - e.g.: imipenem - broad spectrum used when other AB’s have failed or when penicillin allergy

Question 8

What is the MOA for glycopeptide AB’s?
Give examples
What are they used to treat?

Answer 8

• Inhibit cell wall synthesis by blocking incorporation of NAG-NAM-PEP repeat into growing peptidoglycan chain.
• Vancomycin + Teicoplanin
• Used for gram-positive species e.g.: orally for C. difficile

Question 9

What 5 AB groups affect bacterial protein synthesis?

Answer 9

• Tetracyclines
• Amino-glycosides
• Macrolides
• Oxazolidonones
• Lincosamides

Question 10

What is the method of action for tetracycline AB’s?
Give examples
What are they used to treat?
Why don’t you give to children?

Answer 10

• Binds to ribosomes to prevent binding of tRNA to prevent initiation of PS
• Doxycycline (bacteriostatic agents)
• Respiratory tract infections, chlamydia, ache
• Cause staining of developing teeth

Question 11

What is the method of action for aminoglycoside AB’s?
Give examples
What are they used to treat?

Answer 11

• Bind to ribosomes, cause misreading of mRNA and insertion of incorrect AA leading to loss of function (bactericidal)
• Gentamicin
• Used against gram-negative but potentially nephro/ototoxic

Question 12

What is the method of action for macrolide AB’s?
Give examples
What are they used to treat?

Answer 12

• Inhibit ribosomal translocation (static and/or cidal)
• Clarithyromycin/erythromycin
• Similar spectrum to penicillin, also for atypical respiratory pathogens

Question 13

Describe the MOA for oxazolidinones
Give examples
What are lincosamides (with same MOA as macrolides) used to treat?

Answer 13

• Prevent PS
• Broad spec - suited to gram positive e.g.: skin/soft tissue infections (linezolid)
• Gram-positive cocci + anaerobic bacteria (clindamycin)

Question 14

What is the MOA for quinolones?
Give examples
What are they used to treat?

Answer 14

• Inhibit topoisomerase ll (DNA gyrase), stops supercoiling and prevents transcription
• Ciprofloxacin
• Gram-negative organism, complicated UTI’s, gonorrhoea

Question 15

What are the 2 AB’s that interfere with folate synthesis/action. How do they work?
What are they used for?

Answer 15

1) Sulfonamides - mimic PABA and competes with it for dihydropteroate synthetase active site reducing production of folic acid (bacteriostatic) - not often used for infection
2) Trimethoprim - inhibitor of dihydrofolate reductase, prevents production of THF acid - used for UTI’s

Question 16

What is metronidazole used against?

Answer 16

• Exact mechanism unknown
• Thought anaerobic bacteria + protozoa metabolise it making it active in blocking nucleic acid synthesis
• Has disulfuram action - must avoid drinking alcohol (nausea + headaches).

Question 17

What are the 2 main groups of antifungals and their MOA’s? - Give examples

Answer 17

1) Azoles - Inhibit fungal CP4503A enzyme, prevents formation of ergosterol which inhibits replication. E.g.: clotrimazole. Useful for candida infections.
2) Polyenes - lodge in fungal cell wall and alter cellular permeability - e.g.: amphotericin (systemic fungal infections) and nystatin (topical candida)

Question 18

Name 2 commonly used antiviral drugs and describe their MOA

Answer 18

1) Acyclovir - only activated in infected cells as viral thymidine kinase activates it, inhibits DNA polymerase. Used in herpes simplex + VZV
2) Oseltamivir - prevents viral replication by inhibiting neuraminidase which cleaves bonds linking particle coat and host scialic acid. used for influenza A+B.