Antibiotics

Question 1

Why are antimicrobials so important?

Answer 1

Before anti-microbials, 90% of children with bacterial meningitis died. Strep throat was at times fatal, and ear infections sometimes spread to the brain. A third of patients with pneumonia died.

Question 2

What is meant by selective toxicity?

Answer 2

Compounds harm pathogen not host.

Question 3

What was the first effective antisyphilitic discovered in 1909?

Answer 3

“Salvarsan”

Arsenic containing

Question 4

When was penicillin discovered and by who?

Answer 4

1928

Fleming

Question 5

When was prontosil discovered?

Answer 5

1932

Domagk

Question 6

Define antimicrobial.

Answer 6

Any substance active against microbes

Question 7

Define antibiotic.

Answer 7

A naturally occurring product active against bacteria

Question 8

Define broad spectrum.

Answer 8

Kills most germs Gram positive and Negative + or –

anaerobes

Question 9

Define narrow spectrum.

Answer 9

Kills narrow range of microbes

Question 10

Define bactericidal.

Answer 10

Actively kills bacteria

Question 11

Define bacteriostatic.

Answer 11

Prevents bacteria multiplying

Question 12

Bacteriostatic vs Bactericidal - depends on..? (2)

Answer 12

– Microorganism (bacterial inoculum)

– antibiotic concentration

Question 13

When is bactericidal preferred? (2)

Answer 13

When inadequate penetration to infection site e.g. endocarditis, meningitis, osteomyelitis
If immune system is compromised e.g. neutropenia, renal failure, diabetes

Question 14

Give examples of bacteriostatic antibiotics. (6)

Answer 14

Chloramphenicol
Clindamycin
Erythromycin
Tetracyclines
Trimethoprim
Sulfonamides

Question 15

Give examples of bacteriocidal antibiotics. (6)

Answer 15

Aminoglycosides
Beta lactams
Vancomycin
Quinolones
Rifampin
Metronidazole

Question 16

Describe a synergistic antimicrobial combination.

Give an example.

Answer 16

Their combined activity is greater than the sum of the individual activities – e.g B-lactam and aminoglycoside

Question 17

Describe a antagonistic antimicrobial combination.

Give two examples.

Answer 17

The activity of one drug is compromised by the other – e.g Tetracycline or Chloramphenicol associated with B-lactam or aminoglycoside, or 2 B-lactams together

Question 18

Describe the Therapeutic Index curve.

Answer 18

Antimicrobial conc over time - begins sub-therapeutic, then goes to therapeutic, and if rises too high = toxic. Then reduces back down into sub-therapeutic. The therapeutic range is between sub-therapeutic and toxic.

Question 19

What is the therapeutic index?

Answer 19

Therapeutic Index = Toxic / Therapeutic

Question 20

Give an example of an antimicrobial with a high therapeutic index.

Answer 20

Beta lactams

Question 21

Give an example of an antimicrobial with a low therapeutic index.

Answer 21

Aminoglycosides

Question 22

Beta lactams - bacteriostatic or bacteriocidal? 
How do they work?
What other class works in the same way?

Answer 22

Bactericidal
Aim against cell wall synthesis. They make a hole in the bacterial wall and cells die as they can’t maintain osmosis.
Glycopeptides

Question 23

How do quinolones work?

Answer 23

Works against DNA gyrase

Question 24

How does metronidazole work?

Answer 24

Stops DNA replication

Question 25

Which antimicrobial works on DNA-directed RNA polymerase?

Answer 25

Rifampicin

Question 26

Which antimicrobials work on protein synthesis? (5)

Answer 26

50S inhibitors - chloramphenicol, macrolide, clindamycin | 30S inhibitors - aminoglycosides, tetracyclines

Question 27

Which antimicrobials work on folic acid metabolism? (2)

Answer 27

Trimethoprim | Sulfonamides

Question 28

Are most hospital infections gram positive or negative? Why is this an issue?

Answer 28

Negative | Most antimicrobials are for gram positive

Question 29

Give some examples of anti-Gram-positive antimicrobials.

Answer 29

``` Penicillins Fusidic acid Macrolides Clindamycin Glycopeptides Oxazolidinones Daptomycin ```

Question 30

Effective C diff antimicrobial

Answer 30

Glycopeptides e.g. vancomycin

Question 31

Give some examples of anti-Gram-negative antimicrobials.

Answer 31

``` Polymyxin (Colistin) Trimethoprim Aminoglycosides Monobactams (Aztreonam) Temocillin ```

Question 32

Give some examples of broad spectrum antimicrobials.

Answer 32

Beta lactams - Carbapenems, Amoxicillin/clavulanate, Piperacillin/tazobactam, Cephalosporins Chloramphenicol Tetracycline

Question 33

Why is Chloramphenicol not used a lot anymore?

Answer 33

Due to adverse reactions

Question 34

Which two antimicrobials classes act on peptidoglycan/bacterial cell wall synthesis?

Answer 34

Beta-lactam | Glycopeptides

Question 35

Penicillins used in Barts Trust include..?

Answer 35

Penicillin V (oral) Benzylpenicillin (iv) Flucloxacillin (oral and iv) Amoxicillin +/– clavulanic acid (a beta-lactamase inhibitor) (oral and iv) Piperacillin + tazobactam (a beta-lactamase inhibitor)

Question 36

Penicillin - mechanism of action and spectrum? | Route of administration?

Answer 36

Inhibit cell wall synthesis Gram + Oral and IV • Side-effects: rule out penicillin allergy immediate IgE mediated anaphylaxis (0.05%); safe in pregnancy and in children, Jarisch Herxheimer reaction, Coombs positive haemoytic anaemia, interstitial nephritis, serum sickness, hepatitis, drug fever

Question 37

Why does penicillin need to be given 4-6 times a day?

Answer 37

Rapidly excreted

Question 38

Penicillin - penetration? Side effects? Interactions?

Answer 38

penetrates most tissues including inflamed meninges side effects - rule out penicillin allergy immediate IgE mediated anaphylaxis (0.05%); safe in pregnancy and in children, Jarisch Herxheimer reaction, Coombs positive haemoytic anaemia, interstitial nephritis, serum sickness, hepatitis, drug fever Interactions: Allopurinol, methotrexate

Question 39

Penicillin - resistance and mechanism of resistance?

Answer 39

>80% of staphylococci resistant; S. pneumoniae resistance in USA, S. Europe; gonococcal resistance worldwide Mechanism: production of B-lactamase and alteration of PBPs

Question 40

Penicillin - clinical uses?

Answer 40

drug of choice streptococcal and meningococcal disease e.g. meningitis, pneumonia and respiratory infections, syphilis,

Question 41

Amoxicillin mechanism of action.

Answer 41

inhibit cell wall synthesis

Question 42

Amoxicillin dosing regimen.

Answer 42

Three times a day

Question 43

Amoxicillin penetration.

Answer 43

penetrates most tissues including inflamed meninges

Question 44

Side-effects of amoxicillin.

Answer 44

rule out penicillin allergy; safe in pregnancy and in children. AAD*, fever, neutropenia, eosinophilia, rash with monucleosis, increased PT, Kounis syndrome

Question 45

Clinical uses of amoxicillin.

Answer 45

drug of choice for streptococcal disease except when | used empirically for a sore throat; listeria

Question 46

Mechanism of penicillin.

Answer 46

bactericidal, inhibits transpeptidation of cell wall

Question 47

Interactions of amoxicillin.

Answer 47

Allopurinol (rash)