Antibiotics

Question 1

What is the difference between bacteriostatic and bactericidal?

Answer 1

Bateristatic - inhibit bacterial growth
eg. Protein synthesis inhibitors

Bactericidal - kill bacteria
eg. Cell wall-active agents

Question 2

Give an example of antimicrobial synergism?

Answer 2

β-lactam/aminoglycoside combination therapy of streptococcal endocarditis

Question 3

What are the 5 antibiotic targets?

Answer 3

Cell wall
Protein synthesis 
DNA synthesis
RNA synthesis
Plasma membrane

Question 4

Which antimicrobial agents are cell wall synthesis inhibitors?

Answer 4

β-lactams

Glycopeptides

Question 5

What do the β-lactam antibiotics have in common and give some examples

Answer 5

All contain β-lactam ring:
Four-membered ring structure (C-C-C-N)
Structural analogue of D-alanyl-D-alanine

They Interfere with function of “penicillin binding proteins”
Transpeptidases enzymes involved in the peptideoglycan cross-linking

eg. Penicillin’s, Cephalosporin’s, Carbapenems, Monobactams

Question 6

What do Glycopeptides have in common and give some examples

Answer 6

Large molecules, bind directly to terminal D-Alanyl-D-Alanine on NAM pentapeptides
Inhibit binding of transpeptidases and thus peptideoglycan cross-linking
Gram-positive activity
Unable to penetrate Gram-negative outer membrane porins

eg. Vancomycin, teicoplanin

Question 7

What are the antimicrobial agents which inhibit protein synthesis?

Answer 7

Aminoglycosides - eg. Gentamicin

Macrolides - eg. Erythromycin
Lincosamides - eg. Clindamycin
Streptogramins

Tetracyclines - eg. Doxytetracycline

Oxazolidinones - eg. Linezolid

Question 8

What is the specific mechanism of the Aminoglycosides? with examples

Answer 8

Aminoglycosides bind to the 30S ribosomal subunit

Aminoglycosides - eg. Gentamicin, amikacin

Question 9

What is the specific mechanism of the Macrolides, Lincosamides and Streptogramins? with examples

Answer 9

Macrolides, Lincosamides and Streptogramins bind to 50S ribosomal subunit

Blockage of exit tunnel inhibits protein elongation

Macrolides - eg. Erythromycin, clarithromycin

Lincosamides - eg Clindamycin

Question 10

What is the specific mechanism of the Tetracyclines? with examples

Answer 10

Tetracyclines bind to 30S ribosomal subunit.
Inhibit RNA translation by interfering with binding of tRNA to rRNA

eg. tetracycline, doxytetracycline

Question 11

What is the specific mechanism of the Oxazolidinones? with examples

Answer 11

Oxazolidinones bind to 50S ribosomal subunit

They prevent the assembly of initiation complex

eg. Linezolid

Question 12

What are the antimicrobial agents that inhibit DNA synthesis?

Answer 12

Trimethoprim and Sulfonamides
eg. combined = co-trimoxazole

Quinolones and fluoroquinolones
eg. Nalidixic acid, ciprofloxacin, levofloxacin

Question 13

What is the specific mechanism of Trimethoprim and Sulfonamides?

Answer 13

They inhibit folate synthesis
Folic acid is a purine synthesis precursor

Trimethoprim inhibits dihydrofolate reductase

Sulfonamides inhibit dihydropteroate synthetase

Question 14

What antimicrobial is an RNA synthesis inhibitor and what is its mechanism?

Answer 14

Rifampicin

RNA polymerase inhibitor
Prevents synthesis of mRNA

Question 15

Which antimicrobials attack the plasma membrane?

Answer 15

Colistin (Gram-negatives)
Daptomycin (Gram-positives)

Cyclic lipopeptides which cause destruction of cell membranes

Question 16

What are the antibiotic-specific adverse effects of aminoglycosides?

Answer 16

Reversible renal impairment on accumulation
Irreversible ototoxicity (toxic to cochlear nerve)
Therapeutic drug monitoring indicated

Question 17

What are the antibiotic-specific adverse effects of β-lactams?

Answer 17

Allergic reactions:
Generalised rash 1-10%
Anaphylaxis approx. 0.01%

Question 18

What are the antibiotic-specific adverse effects of Linezolid?

Answer 18

Bone marrow depression

Question 19

Which antibiotics are the most common for precipitating a C. difficile infection

Answer 19

4Cs
Co-amoxiclav (amoxicilin-clavulanate)
Cephalosporins
Ciprofloxacin
Clindamycin

Question 20

What are the 6 methods a bacteria can use to become resistant to antibiotics?

Answer 20

No target – no effect
Reduced permeability – drug can’t get in
Altered target – no effect
Over-expression of target – effect diluted
Enzymatic degradation – drug destroyed
Efflux pump – drug expelled

Question 21

Why is vancomycin ineffective against gram-ve bacilli?

Answer 21

Gram-negatives have an outer membrane that is impermeable to vancomycin

Question 22

Why is Gentamicin ineffective against anaerobic organism?

Answer 22

Uptake of aminoglycosides requires an O2 dependent active transport mechanism

Question 23

How has MRSA developed resistance to flucloxacillin?

Answer 23

Altered penicillin-binding protein (PBP2’, encoded by MecA gene) does not bind β-lactams

Question 24

How has VRE (vancomycin resistant enterococci) developed resistance?

Answer 24

Altered peptide sequence in Gram-positive peptideoglycan, reduces binding of vancomycin 1000 fold

Question 25

How have some gram-ve bacilli become resistant to Trimethoprim?

Answer 25

Mutations in the dihydrofolate reductase gene

Question 26

Give two examples of bacteria using enzyme degradation to become resistant to antibiotics

Answer 26

Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL) are resistant to penicillin’s and cephalosporin’s

Aminoglycoside-modifying enzymes provide resistance against Gentamicin

Question 27

What is horizontal transfer?

Answer 27

Antibiotic resistance gene is put into a plasmid

Plasmid transferred between organisms by conjugation

Question 28

What is the treatment for strep pyogenes infection?

Answer 28

Benzylpenicillin

Question 29

Which antibiotic is used to treat MRSA?

Answer 29

Vancomycin

Question 30

What is the specific mechanism of the quinolones and fluoroquinalones? with examples

Answer 30

Inhibit one or more of two related enzymes:
DNA gyrase and topoisomerase II

Involved in remodelling of DNA during DNA replication

Question 31

What is in co-amixoclav and why?

Answer 31

Amoxicillin - a β-lactam antibiotic, and
clavulanic acid - a β-lactamase inhibitor

Improves the efficacy of amoxicillin against β-lactam resistant bacteria