Antimicrobial Chemotherapy

Question 1

How does Penicillin work? What is its functional unit?

Answer 1

Binding to bacterial transpeptidases, inhibiting cell wall synthesis.
Functional Unit - Beta lactam ring.

Question 2

What examples of Naturally-occurring penicillins and Chemically modified penicillins.

What makes them useful/not useful. (6)

Answer 2

Naturally occuring: Benzylpenicillin - Poor oral bioavailability; rapid renal clearance so needs frequent dosing.

Chemically modified:
- Pen V (Phenoxymethylpenicillin) - Orally active but also rapid renal clearance so need x6 a day.

• Aminopenicillins e.g amoxicillin: It is orally active and less renal clearance so only needs x3 a day.
• Cephalosporins (given IV) - Delayed excretion, altered water solubility, works against different transpeptidases and resitant to degradation by beta lactamase.

Question 3

Amoxicillin:

1. What bacterias can it be used to treat? (3)
2. How do bacteria become resistant to it? (3)
3. What are its adverse effects? (2)

Answer 3

1. Strep Pyogenes (sore throat, skin), Penumococcal (resp tract) infections and some Gram-negatives such as E. Coli (urinary tract)
2. Efflux pumps in some Gram negatives, enzymatic degradation and target modification.
3. Allergy and damage to commensal flora.

Question 4

Why might some penicillins work for some bacteria and not others? (1)

What type of bacteria do most penicillins have no useful activity against? What development addresses this? (2)

Answer 4

Different transpeptidases in different bacteria hence different beta-lactam binding.

Pseudomonas (Gram negative rod, causes wound infections).
Special Antipsesudomonal penicillins (e.g piepracillin).

Question 5

How did Staph Aureus become resistant to Penicllin? What drug and developments solved this? (4)

Answer 5

Resistance (1948) to Penicillins which had ‘penillanase’ which hydrolyse beta-lactamase ring.

Improved drug (1950s): Flucloxacillin.

Development: Beta lactamse inhibitor drug such as Clavulinic acid invented. Not antibiotic but alternative substrate for transpeptidase enzymes hence protects antibiotic from degradation.

Now: Co-Amoxiclav = Amoxicillin plus Clavulinic acid

Question 6

For MRSA’s which are resistant to all beta-lactam penicillins, what was the mechanism? (2)

Answer 6

Target modification - modified transpeptidase enzymes for (mecA gene) to make peptidoglycans.

Question 7

What bacterial actions can Antibiotics target? (5)

Answer 7

1. DNA replication
2. RNA replication
3. Protein Synthesis
4. Cell Wall
5. Metabolism

Question 8

Clarythromycin: Macrolide

1. How do they work?
2. What bacterias do they work against?
3. What bacteria are resistant?
4. What adverse effects (4)

Answer 8

1. They bind to 50s subunit to ribosome and inhibits protein synthesis.
2. Work against gram positives, gram negatives and cell wall deficient bacteria
3. Some Streps due to target site mutation
4. Nausea and diarrhoea, arrhythmias.

Question 9

Vancomycin:

1. How does it work?
2. What bacterias do they work against?
3. How might Bacteria become resistant?
4. What problems might it present? What are its adverse effects?

Answer 9

1. It is a glycopeptide. Works by inhibiting bacterial cell wall formation enzymes by different target to beta lactam.
2. Works only against Gram positives, very good against MRSA.
3. Target mutation and thickening of cell wall to reduce penetration.
4. It has a narrow therapeutic window, levels needed to kill bacteria close to toxic level to patient. Hence can be NEPHROTIC & OXOTOXIC

Question 10

How do Bacteria Genetically become resistant to antibiotics?

Answer 10

1. Mobile genetic elements e.g mecA gene for MRSA; Beta lactamase gene in E.coli.
2. Acquisition of new gene (rare)
3. Spontaenous mutation