T2 - L4 ANTIBACTERIAL AND ANTIFUNGAL AGENTS

Question 1

what do bacteria and fungi have in common?

Answer 1

• cell wall
• cell membrane(s)
• DNA
• synthetic functions - protein synthesis

Question 2

what are the differences in DNA between fungi and bacteria?

Answer 2

bacteria:

• prokaryotes
• DNA is ring like structure in cytoplasm

fungi:

• eukaryotes
• DNA is separated from cytoplasm by nuclear membrane

Question 3

what are the differences in size between fungi and bacteria?

Answer 3

bacterial cells are much smaller than fungal cells

Question 4

what do Bacteriostatic/fungistatic antimicrobials do?

Answer 4

inhibit growth

e.g. protein synthesis inhibitors

Question 5

what do Bacteriocidal/fungicidal

antimicrobials do?

Answer 5

kill

Question 6

what is meant by a minimum inhibitory concentration (MIC)?

Answer 6

Minimum concentration of antimicrobial agent at which visible growth is inhibited

Question 7

what is meant by Minimum bactericidal/fungicidal concentration? (MBC/MFC)

Answer 7

Minimum concentration of antimicrobial agent at which most organisms are killed

Question 8

a low MIC (e.g. 0.1mg/L) would indicate what?

Answer 8

sensitive organism

NB: sensitivity actually depends on the level available at the site of infection

Question 9

what is meant by synergism?

Answer 9

Activity of two antimicrobials given together is greater than the sum of their activity if given separately

the interaction or cooperation of two or more organizations, substances, or other agents to produce a combined effect greater than the sum of their separate effects.

Question 10

what is antagonism?

Answer 10

One antimicrobial agent diminishes the activity of another, when given at the same time

Question 11

what is indifference?

Answer 11

Activity unaffected by the addition of another antimicrobial agent

Question 12

what are broad spectrum antimicrobials?

Answer 12

kills most types of bacteria/fungi encountered

Question 13

what are narrow spectrum antimicrobials?

Answer 13

kills only a narrow range of organisms

Question 14

what are the mechanisms of action of antimicrobials?

Answer 14

Inhibition of critical process in bacterial/fungal cells – ‘antimicrobial targets’

Question 15

antimicrobials need to exhibit “selectivity toxicity” - what does this mean?

Answer 15

their target is not present or inaccessible in a human host

• so they cause no harm to humans

Question 16

list some antimicrobial targets

Answer 16

• Cell wall
• Protein synthesis
• DNA synthesis
• RNA synthesis
• Plasma membrane

Question 17

what are ‘antimicrobial targets’?

Answer 17

things antimicrobials try and target to inhibit critical processes in bacteria/fungi

Question 18

what is a bacterial cell wall made up of?

Answer 18

peptidoglycan

Question 19

why is a bacterial cell wall ideal for selective toxicity?

Answer 19

no cell wall in animal cells

Question 20

what are some antibacterial agents that inhibit cell wall synthesis?

Answer 20

• β-lactams

- Glycopeptides

Question 21

list some β-lactams antibiotics.

Answer 21

• Penicillins
• Cephalosporins
• Carbapenems
• Monobactams

Question 22

Benzylpenicillin is what type of antibiotic?

Answer 22

β-lactams antibiotics

• penicillin
• narrow spectrum

Question 23

amoxicillin is what type of antibiotic?

Answer 23

β-lactams antibiotics

• penicillin
• narrow spectrum

Question 24

flucloxacillin is what type of antibiotic?

Answer 24

β-lactams antibiotics

• penicillin
• narrow spectrum

Question 25

Cefuroxime is what type of antibiotic?

Answer 25

β-lactams antibiotics - Cephalosporins - broad spectrum - arranged into "generations"

Question 26

ceftazidime is what type of antibiotic?

Answer 26

β-lactams antibiotics - Cephalosporins - broad spectrum - arranged into "generations"

Question 27

which β-lactams antibiotics are broad spectrum?

Answer 27

• Cephalosporins - Cefuroxime, ceftazidime etc. • Carbapenems - Meropenem, imipenem

Question 28

Meropenem is what type of antibiotic?

Answer 28

β-lactams antibiotics - carbapenems - extremely broad spectrum

Question 29

imipenem is what type of antibiotic?

Answer 29

β-lactams antibiotics - carbapenems - extremely broad spectrum

Question 30

which β-lactams antibiotics are narrow spectrum?

Answer 30

• Penicillins | - Benzylpenicillin, amoxicillin, flucloxacillin

Question 31

which β-lactams antibiotics are gram-negative acting only?

Answer 31

• Monobactams | - Aztreonam

Question 32

what type of an antibiotic is Aztreonam?

Answer 32

β-lactams antibiotics • Monobactams • gram-negative activity only

Question 33

what are β-lactamase enzymes?

Answer 33

Enzymes that hydrolyse (inactivate) β-lactams

Question 34

what is a common mechanism or resistance to β-lactam antibiotics?

Answer 34

β-lactamase enzymes

Question 35

the β-lactamase enzyme, Staphylococcal β-lactamase, has resistance against what?

Answer 35

some penicillins only

Question 36

the β-lactamase enzyme, ‘Extended spectrum β-lactamase’ (ESBL), has resistance against what?

Answer 36

penicillins and cephalosporins

Question 37

the β-lactamase enzyme, Carbapenemases (eg NDM1), has resistance against what?

Answer 37

carbapenems

Question 38

list some β-lactam/β-lactamase inhibitor combinations (BLBLI).

Answer 38

Amocixillin-clavulanate (Augmentin) Piperacillin-tazobactam (Tazocin)

Question 39

what are some problems with BLBLIs?

Answer 39

• Very broad spectrum, so predispose to C. difficile infection • Names do not end with –illin or start with cef- - Importance of penicillin allergy may be missed

Question 40

antibacterial glycopeptides inhibit what?

Answer 40

bacterial cell wall synthesis

Question 41

give some examples of antibacterial glycopeptides.

Answer 41

vancomycin teicoplanin

Question 42

what type of antibiotic is vancomycin?

Answer 42

Glycopeptides - inhibit bacterial cell wall synthesis

Question 43

what type of antibiotic is teicoplanin?

Answer 43

Glycopeptides - inhibit bacterial cell wall synthesi

Question 44

what is a fungal cell wall made of?

Answer 44

* β-1,3-glucan * chitin * synthesised by β-1,3-glucan synthase

Question 45

what anti fungal agents inhibit cell wall synthesis?

Answer 45

Echinocandins - Anidulafungin - Caspofungin - Micafungin

Question 46

how do Echinocandins inhibit cell wall synthesis of fungi?

Answer 46

- Inhibition of β-1,3-glucan synthase | - Construction of severely abnormal cell wall

Question 47

what type of antimicrobial is Anidulafungin?

Answer 47

- anti fungal agent: Echinocandins | - inhibits cell wall synthesis in fungi

Question 48

what type of antimicrobial is | Caspofungin?

Answer 48

- anti fungal agent: Echinocandins | - inhibits cell wall synthesis in fungi

Question 49

what type of antimicrobial is - Micafungin?

Answer 49

- anti fungal agent: Echinocandins | - inhibits cell wall synthesis in fungi

Question 50

what are the 6 types of protein synthesis inhibitors in bacteria?

Answer 50

1. Aminoglycosides 2. MLS antibiotics 3. Tetracyclines 4. Oxazolidinones 5. Mupirocin 6. Fusidic acid

Question 51

list some aminoglycosides

Answer 51

* Gentamicin, amikacin | * Bind to 30S ribosomal subunit

Question 52

what type of antibiotic is Gentamicin?

Answer 52

- aminoglycosides | - targets protein synthesis in bacteria

Question 53

what type of antibiotic is amikacin?

Answer 53

- aminoglycosides | - targets protein synthesis in bacteria

Question 54

list some MLS antibiotics

Answer 54

• Macrolides, Lincosamides, Streptogramins - Erythromycin, clarithromycin (macrolides) - Clindamycin (lincosamide) * Bind to 50S ribosomal subunit * Inhibit protein elongation

Question 55

list some tetracycline antibiotics

Answer 55

Tetracycline, doxycycline. - Bind to 30S ribosomal subunit. - Inhibit translation by interfering with binding of tRNA to rRNA.

Question 56

name an oxazolidinone antibiotic

Answer 56

Linezolid - Inhibits initiation of protein synthesis - Binds to 50S ribosomal subunit - Inhibits assembly of initiation complex - May also bind to 70S subunit

Question 57

what type of antibiotic is Erythromycin, and what does it inhibit?

Answer 57

MLS antibiotics - macrolides inhibits protein elongation (targets protein synthesis)

Question 58

what type of antibiotic is clarithromycin, and what does it inhibit?

Answer 58

MLS antibiotics - macrolides inhibits protein elongation (targets protein synthesis)

Question 59

what type of antibiotic is Clindamycin, and what does it inhibit?

Answer 59

MLS antibiotics - lincosamide inhibits protein elongation (targets protein synthesis)

Question 60

what type of protein synthesis inhibitors in bacteria Inhibit translation by interfering with binding of tRNA to rRNA?

Answer 60

Tetracyclines Tetracycline, doxycycline.

Question 61

what type of protein synthesis inhibitors in bacteria Inhibit protein elongation?

Answer 61

MLS antibiotics - Erythromycin, clarithromycin (macrolides) - Clindamycin (lincosamide)

Question 62

what type of protein synthesis inhibitors in bacteria Inhibits the initiation of protein synthesis?

Answer 62

Oxazolidinones • Linezolid

Question 63

which antimicrobials inhibit DNA synthesis in bacteria?

Answer 63

trimethoprim sulfonamides quinolones fluoroquinolones

Question 64

how do trimethoprim and sulfonamides inhibit DNA synthesis in bacteria?

Answer 64

• Both agents inhibit folate synthesis - Trimethoprim - dihydrofolate reductase - Sulfonamides - dihydropteroate synthetase

Question 65

Trimethoprim is commonly used to treat what?

Answer 65

UTI

Question 66

how do quinolones and fluoroquinolones | inhibit DNA synthesis in bacteria?

Answer 66

• Inhibit one or more of two related bacterial enzymes - DNA gyrase and topoisomerase IV - Involved in remodelling of DNA during DNA replication

Question 67

which antimicrobial agent inhibits DNA gyrase and topoisomerase?

Answer 67

quinolones and fluoroquinolones

Question 68

Quinolones are effective against bacteria only; true or false?

Answer 68

true

Question 69

what anti fungal agent inhibits DNA synthesis in fungi?

Answer 69

5 fluorocytosine (5FC) • Selectively taken into fungal cells by a fungal enzyme (cytosine permease)

Question 70

what antimicrobial agent prevents the synthesis of mRNA?

Answer 70

• Rifampicin - RNA polymerase inhibitor - Prevents synthesis of mRNA • Cornerstone of anti-tuberculous chemotherapy

Question 71

which antibacterial agents target the cell membrane in bacteria?

Answer 71

* Colistin (Gram-negatives)1 * Daptomycin (Gram-positives)2 - Cyclic lipopeptides - Destruction of outer membrane1/cytoplasmic membrane

Question 72

which anti fungal agents target the cell membrane in fungi?

Answer 72

* Azoles (eg clotrimazole, fluconazole) * Terbinafine * Amphotericin B

Question 73

why would we combine antimicrobial agents?

Answer 73

• To provide adequately broad spectrum • To increase efficacy - Synergistic combination may improve outcome • To reduce resistance - Organism would need to develop resistance to multiple agents simultaneously