Lecture 8: Antimicrobial Chemotherapy

Question 1

How do penicillin’s work?

Answer 1

Penicillin’s act by binding bacterial transpeptidases (enzymes involved in peptidoglycans synthesis in both gram positive and gram negative bacteria) to inhibit cell wall formation.

Question 2

Why can penicillin not be given to individuals with kidney problems?

Answer 2

Penicillin’s and beta-lactams are excreted intact in urine so cannot be given to individuals with kidney problems.

Question 3

What is Benzylpenicillin (penicillin G)?

Answer 3

A naturally occurring penicillin that has poor oral bioavailability. Rapid renal clearance so requires frequent dosing.

Question 4

What is Phenoxymethylpenicillin (Pen V)?

Answer 4

A chemically modified penicillin that is orally active but still has rapid renal clearance.

Question 5

What is amoxicillin?

Answer 5

A chemically modified penicillin that has good oral bioavailability, a longer half-life than penicillin V, and better activity against some Gram negative bacteria.

Question 6

Where is amoxicillin used?

Answer 6

Used in the treatment of S. pyogenes infections (sore throat, skin infections), pneumococcal infections (respiratory tract) and susceptible E. coli infections (urinary tract infection).

Question 7

What is the mechanism of amoxicillin resistance?

Answer 7

Primarily enzymatic degradation and efflux in some gram negative bacteria’s.

Question 8

What are the adverse effects of amoxicillin?

Answer 8

Allergy and damage to commensal microflora.

Question 9

What are the 4 main ways bacteria become resistant to antibiotics?

Answer 9

1. Enzymatic degradation
2. Target modification
3. Antibiotic efflux
4. Reduced penetration through the cell wall

Question 10

Why are different penicillin’s needed for different bacteria?

Answer 10

Different bacterial species have different transpeptidases (PBPs), which have the same function but different beta-lactam binding, and so different penicillin’s are required to treat them

Question 11

How do enzymatic degradation mediate antibiotic resistance?

Answer 11

Enzymes hydrolyse the beta-lactam ring of penicillin “penicillinases” and this confers their resistance. Bacteria have gained a gene-encoded enzyme that breaks down beta-lactamase ring of penicillin.

Question 12

What type of penicillin is able to treat bacteria that have a gene-encoded enzyme that breaks down beta-lactam ring?

Answer 12

Flucloxacillin

Question 13

What is an example of a beta-lactamase inhibitor drug?

Answer 13

Co-amoxiclav

Question 14

What causes antibiotic resistance?

Answer 14

Antibiotic resistance is an inevitable consequence of use. Antibiotic misuse leads to more resistance.

Question 15

What is the most common pathogen causing cellulitis?

Answer 15

Streptococcus pyogenes (or S.aureus)

Question 16

How does the drug clarithromycin work?

Answer 16

Clarithromycin is a macrolide which binds to 50S subunit of bacterial ribosome to block protein synthesis.

Question 17

What are the adverse effects of clarithromycin?

Answer 17

Nausea and diarrhoea, and may alter cardiac conduction and cause arrhythmias.

Question 18

What are the mechanisms of resistance to clarithromycin?

Answer 18

Primarily mutational target modification.

Question 19

Why don’t antibiotics always work?

Answer 19

Metabolism, poor dispersal of antibiotics, multiple bacterial infections, and poor compliance with antibiotics. Antibiotics can also select out commensals which may then cause other infections.

Question 20

How does vancomycin work?

Answer 20

Vancomycin is a glycopeptide drug that inhibits bacterial cell wall (peptidoglycans) formation by a different target to beta lactams.

Question 21

What bacteria is vancomycin used against?

Answer 21

Used against Gram positive bacterial infections and is also active against many resistant strains including MRSA.

Question 22

What are the adverse effects of vancomycin?

Answer 22

Nephrotoxic and ototoxic

Question 23

What are the mechanisms of resistance against vancomycin?

Answer 23

Target modification and cell wall thickening of bacteria resulting in reduced penetration of drugs.

Question 24

How are bacteria genetic modified to be resistant?

Answer 24

1. Mobile genetic elements

2. Spontaneous mutations