MI: Antimicrobials 1 Pt.1

Question 1

Examples of selective targets for antibiotics

Answer 1

Peptidoglycan layer of cell wall

Inhibition of bacterial protein synthesis

Inhibition of DNA gyrase and other prokaryote specific enzymes

Question 2

What is the broad mechanism of action of beta lactams?

Answer 2

Inhibition of cell wall synthesis

Question 3

What is the broad mechanism of action of glycopeptide antibiotics?

Answer 3

Inhibition of cell wall synthesis

Question 4

What 3 groups of antibiotics are classified as beta lactams?

Answer 4

Penicillins

Cephalosporins

Carbapenems

Question 5

Name 2 glycopeptide antibiotics

Answer 5

Vancomycin

Teicoplanin

Question 6

Describe the mechanism of action of beta lactams

Answer 6

Inhibits transpeptidase, which is an enzyme that forms cross links during the formation of the cell wall.

The resulting cell wall is therefore weak, and so the bacteria lyse because of osmotic pressure.

*They are effective against rapidly dividing bacteria - not useful if the cell wall has already been formed*

Question 7

How does the cell wall of gram pos and gram neg bacteria differ?

Answer 7

Gram pos: thick peptidoglycan layer, no outer membrane

Gram neg: thin peptidoglycan layer, has an outer membrane (some antibiotics can’t get through this)

*Gram pos stain purple, gram neg stain pink*

Question 8

What bacteria is penicillin active against?

Answer 8

Gram pos

Not effective against organisms with no peptidoglycan cell wall e.g. mycoplasma and chlamydia

Question 9

What bacteria is amoxicillin active against?

Answer 9

Broad spectrum: gram pos and many gram neg

*Broken down by beta lactamase produced by S. aureus and other microorganisms*

Question 10

Which beta lactam antibiotic is effective against pseudomonas?

Answer 10

Piperacillin

*Broken down by beta lactamase*

That’s why it’s used as tazocin

Question 11

How can beta lactam resistance be overcome?

Answer 11

Include a beta lactamase inhibitor

Eg. Clavulanic acid + amoxicllin (in co-amoxiclav aka augmentin)

Eg. Tazobactam + piperacillin (in tazocin)

Alternatively, create antibiotics that are stable to beta lactamase eg. flucloxacillin

Question 12

Recall an antibiotic that is associated with C. difficile

Answer 12

Ceftriaxone (cephalosporin)

Question 13

Examples of cephalosporins

Answer 13

Cefalexin (1st generation)

Cefuroxime (2nd generation)

Ceftriaxone (3rd generation)

Ceftazidime (3rd generation)

Cefotaxime (3rd generation, paediatric cefotriaxone)

*As cephalosporins progressed from 1st to 3rd generation, they became more effective against gram negative and less effective against gram positive*

Question 14

What limits the use of cephalosporins?

Answer 14

Extended spectrum beta lactamase (ESBL) producing organisms are resistant to cephalosporins

Question 15

Which beta lactam antibiotics are stable to ESBL organisms?

Answer 15

Carbapenems

*However, carbapenemase enzyme producing organisms (acinetobacter and klebsiella) are becoming more prevalent*

Question 16

Recall the key features of beta lactams

Answer 16

Relatively non-toxic

Renally excreted so decrease dose if renal impairment

Short T1/2 (many are type 2/time-dependent drugs so aim to maximise the time where concentration > MIC)

Will not cross intact BBB (but can cross in meningitis)

Cross allergenic – penicillin has 10% cross reactivity with cephalosporins and carbapenems

Question 17

What type of bacteria are glycopeptides effective against?

Answer 17

Gram pos only - they are large molecules so can’t penetrate gram neg cell wall

Question 18

What are glycopeptides particularly useful for?

Answer 18

MRSA infection

Question 19

What is a caution of glycopeptide antibiotics?

Answer 19

They are nephrotoxic

Question 20

Recall the broad mechanism of action of glycopeptide antibiotics

Answer 20

Prevent peptide cross links in cell wall

They bind to the amino acid chains at the end of peptidoglycan precursors, to prevent glycosidic bond formation. They prevent transpeptidase activity without directly binding to the enzyme.

Question 21

Recall the broad mechanism of action of aminoglycosides

Answer 21

Bind to 30s ribosomal subunit, preventing elongation of polypeptide chain

*This doesn’t explain their rapid bactericidal activity - full mechanism is unknown*

Question 22

Recall 2 examples of aminoglycoside antibiotics

Answer 22

gentamicin

amikacin

Question 23

What type of bacteria are aminoglycoside antibiotics effective against?

Answer 23

Gram neg

Aerobes (no activity against anaerobes)

Question 24

Recall 2 toxicities of aminoglycosides

Answer 24

Ototoxicity

Nephrotoxicity

Question 25

What type of bacteria are macrolides effective against?

Answer 25

Gram pos