Theme 3: Lecture 13 - antibacterials and antifungals

Question 1

What are antibiotics?

Answer 1

chemical products of microbes that inhibit or kill other organisms

Question 2

What is bacteriostatic/ fungistatic killing?

Answer 2

• inhibit growth (as oppose to killing the organism)

- mainly protein synthesis inhibitors

Question 3

What is bacteriocidal/fungicidal?

Answer 3

• cause cell death

- mainly cell wall-active agents

Question 4

What is Minimum inhibitory concentration (MIC)?

Answer 4

• minimum concentration of antimicrobial agent at which visible growth is inhibited
• so the lower the MIC, the more sensitive the organism is to the antimicrobial

Question 5

What is synergy?

Answer 5

a combination is considered to be synergistic when the effect observed with a combination is greater than the sum of the effects observed with the two drugs independently

Question 6

What is antagonism?

Answer 6

activity of two antimicrobials given together is less than the activity if given separately

Question 7

Whats the difference between broad spectrum and narrow spectrum antibiotics?

Answer 7

broad spectrum - kills most types of bacteria/fungi encountered
narrow spectrum - kills only a narrow range of organisms

Question 8

Why does the spectrum of organisms covered by an antimicrobial agent become narrower during its clinical lifespan?

Answer 8

resistance develops in the target microbial population

Question 9

Is penicillin broad spectrum or narrow spectrum?

Answer 9

was once broad spectrum but now considered to be narrow spectrum

Question 10

What is peptidoglycan?

Answer 10

• murein

- major structural component of bacterial cell wall

Question 11

What are PBPs?

Answer 11

• penicillin binding proteins

- enzymes involved in the synthesis and maintenance of peptidoglycan

Question 12

What are the 2 groups of antibiotics that are cell wall synthesis inhibitors?

Answer 12

• B-lactams

- glycopeptides

Question 13

What was the first true antibiotic in clinical practise?

Answer 13

• benzylpenicillin

- a B lactam

Question 14

What do all B-lactams contain and what is their mechanism of action?

Answer 14

• all contain B-lactam ring

- mechanism of action is inhibition of PBPs

Question 15

Give 4 groups of B-lactam antibiotics and some examples of each

Answer 15

1. pencillins - narrow spectrum
   - benzylpenicillin
   - amoxicillin
   - flucloxacillin
2. cephalosporins - broad spectrum
   - cefuroxime
3. carbapenems - broad spectrum
   - meropenem
4. monobactams - gram negative
   - aztreonam

Question 16

Give two examples of antibiotics that are glycopeptides?

Answer 16

vancomycin and teicoplanin

Question 17

How do glycopeptides work?

Answer 17

• inhibit binding of transpeptidases and thus peptideoglycan cross linking
• gram +ve activity
• unable to penetrate gram negative outer membrane

Question 18

Give the names of some antibacterials that inhibit the protein synthesis in bacteria?

Answer 18

-aminoglycosides e.g gentamicin
-macrolides e.g clarithromycin
-tetracyclin, doxycycline
-linezolid (gram +ve)
and some more

Question 19

What are the 3 main groups of DNA synthesis inhibitors?

Answer 19

• trimethoprim
• sulfonamides
• fluoroquinolones

Question 20

How do trimethoprim and sulfonamide work?

Answer 20

• both agents inhibit folate synthesis
• sulfonamides inhibit dihydropteroate synthetase
• trimethoprim inhibits dihydrofolate reductase

Question 21

What are some examples of DNA synthesis inhibitors?

Answer 21

ciprofloxacin, levofloxacine

Question 22

What is rifampicin? How does it work and what is it used for?

Answer 22

• RNA synthesis inhibitor
• inhibits RNA polymerase
• prevents synthesis of mRNA
• main use is to treat tuberculosis

Question 23

Which antibiotics work on cell membranes?

Answer 23

gram negatives - colistin

gram positives - daptomycin

Question 24

How are fungi classified and which fungi dosen’t fit into these categories

Answer 24

• fungi are classified as moulds/filamentous fungi or yeasts

- pneumocystis jiroveci dosen’t fit into these categories

Question 25

What is a fungal cell wall made of?

Answer 25

-B-1,3-glucan

Question 26

What is B-1,3-glucan synthesised by?

Answer 26

B-1,3-glucan synthase

Question 27

Why is ergosterol in fungal cells a target for selective toxicity?

Answer 27

fufils the same function as cholesterol in animal cells but it is different in fungal cells so this can be manipulated

Question 28

How do antifungal cell wall inhibitors work and what are some examples?

Answer 28

• echinocandins (antifungal)
• inhibit B-1,3-glucan synthase
• examples are caspofungin and anidulafungin

Question 29

What are 3 classes of antifungal cell membrane agents

Answer 29

1. azoles e.g clotrimazole, fluconazole, voriconazole
2. terbafine
3. amphotericin B

Question 30

How does terbinafine and azoles work?

Answer 30

inhibit synthesis of ergosterol (a component of fungal cell membranes but not human or bacterial)

Question 31

How does amphotericin B work?

Answer 31

binds to ergosterol causing physical damage to the membrane

Question 32

Which antifungal agent is involved in RNA/DNA synthesis inhibition?

Answer 32

5-flurocytosine

Question 33

What are the 3 types of antimicrobial therapy you can give patients?

Answer 33

1. empiric therapy
   - initial selection of antimicrobial agents of broad enough spectrum to cover the range of organisms likely to be causing the patients infection
2. targeted therapy
   - use of narrowest-possible spectrum agents
3. susceptibility guided therapy
   - based on susceptibility testing results