3 Bacterial targets for therapy

Question 1

Give some common features of antibiotics (successful abx)

Answer 1

• Selective toxicity
• Drugs that get to the site of infection
• Overcome bacterial resistances to kill or stop them from growing

Question 2

List some bacterial targets that antibiotics target:

Answer 2

• Cell wall (synthesis)
• Protein synthesis
• Cell membrane
• DNA synthesis/replication

Question 3

Name the antibiotic types that target the cell wall

Answer 3

• Beta lactams

- Glycopeptide

Question 4

Describe beta-lactams

Answer 4

A type of antibody that targets cell wall
- They are bactericidal
- examples are:
> Penicillin, cephalosporins, carbapenems, monobactams
- they share a common ring structure (e.g. if someone is allergic to cephalosporins, they are most likely going to be allergic to another beta-lactam, like penicillin)

Question 5

Describe the mechanism of action of beta-lactams (like penicillin)

Answer 5

• The cell wall of bacteria involves sheets linked together (which maintain structural integrity)
• B-lactams block bacterial cell wall mucopeptide formation by binding to and inactivating specific penicillin-binding proteins (PBPs)
  > PBPs are peptidases involved in the final stages of cell wall assembly and division

Question 6

Explain how some bacteria may be resistant to the antibiotic actions of beta-lactams

Answer 6

Some bacteria have Beta-lactamases (enzymes on bacteria), which destroy the antibiotics and create resistance

Question 7

Explain how the issue of beta-lactam resistance is overcome (Beta lactamases)

Answer 7

With penicillin, clavulanic acid is included with some agents (e.g. amoxicillin) to inhibit the beta-lactamases

Co-amoxiclav = Amoxicillin + Clavulanic Acid

Question 8

Give some uses of Beta-lactams as an antibiotic

Answer 8

• Flucloxacillin: Given to cellulitis (skin bacterial infection)
• Ciprofloxacin - Given to septic arthritis
• Co-amoxiclav - given for pneumonia (against pneumococcus - most common causative agents of community-acquired pneumonia)

Question 9

Describe glycopeptides

Answer 9

They are bactericidal

• e.g. Vancomycin
• used against gram +ve bacteria, where resistance is suspected
• It is used if an immediate therapeutic activity is needed

e.g. Used in endocarditis

Question 10

Name the antibiotic types that target protein synthesis

Answer 10

• Aminoglycosides
• Tetracyclines and glycylcyclines
• Macrolides

Question 11

Describe aminoglycosides

Answer 11

These antibiotics are polycationic compounds of amino sugars

- They target protein synthesis

Question 12

Give the mechanism of action of aminoglycoside abx

Answer 12

Aminoglycosides interrupt bacterial protein synthesis by inhibiting the ribosomal function
- Messenger and Transfer RNA

Question 13

Give some examples of aminoglycoside antibiotics

Answer 13

• Streptomycin (rarely used)
• Neomycin (gut sterilization/colonic bacterial load reduction in hepatic failure)
• Gentamycin + tobramycin (both bacteri - static + cidal)
  > levels need to be carefully monitored
  > small TW - it can be ototoxic and nephrotoxic)

Question 14

Describe the MOA of tetracyclines and glycylcyclines

Answer 14

Tetracyclines inhibit bacterial protein synthesis by interrupting the ribosomal function
- Transfer RNA

Question 15

Give some examples of Tetracyclines

Answer 15

• Tetracyclines (named abx and class)
• Oxytetracycline
• Demeclocycline
• Lymecycline
• Doxycycline (bacteriostatic)
• Minocycline

Question 16

Give some uses of Tetracyclines

Answer 16

Tetracyclines are active against:
- Gram +ve and Gram -ve bacteria

but their use is limited, partly owing to increasing bacterial resistance

Question 17

Describe macrolides

Answer 17

• They target cell wall synthesis

Question 18

Give some examples of macrolides

Answer 18

• Erythromycin

- Clarithromycin

Question 19

Describe some implications of the use of macrolides (clarithromycin)

Answer 19

Clarithromycin has a similar (not identical) antibacterial spectrum to penicillin
- and maybe useful in individuals with penicillin allergy, especially in the management of bacterial respiratory infections

Question 20

Name the antibiotic types that target DNA synthesis

Answer 20

• Sulphonamides and trimethoprim

- Quinolones

Question 21

Describe sulphonamide’s MOA

Answer 21

• Sulphonamides block thymidine and purine synthesis by inhibiting the microbial folic acid synthesis

Question 22

Describe the mechanism of action of trimethoprim

Answer 22

• Trimethoprim prevents the reduction of dihydrofolate to tetrahydrofolate (involved in DNA synthesis)

Question 23

Describe the use of sulphamethoxazole (sulphonamides)

Answer 23

Sulphamethoxazole is mainly used in combination with trimethoprim (as cotrimoxazole)
- Its use is now largely restricted to the treatment and prevention of Pneumocystis jeroveci infection and listeriosis in developed countries

Question 24

Describe the use of Trimethoprim

Answer 24

Trimethoprim is often used for urinary tract infections (through usually Nitrofurantoin)

Question 25

Describe quinolones

Answer 25

Quinolone antibiotics are useful oral broad-spectrum antibiotics

• Used against gram -ve bacteria
• Given for urinary sepsis
• Bioavailability (F) - as good as orally as by IV infusion

They are both:

• Bactericidal
• Bacteriostatic

Question 26

Describe Antibiotic resistance

Answer 26

Occurs when bacteria change in response to the use of antibiotics used to treat bacterial infections, like:
- UTI, pneumonia, bloodstream infections)

Question 27

List the different mechanisms of actions of antibiotic resistance

Answer 27

• Resistance to an antibiotic can be the result of impaired or altered permeability of the bacterial cell envelope e.g. Penicillin in gram -ve bacteria
• Active expulsions from the cell by membrane efflux systems (alteration of the target site, overproduction of target site, or specific enzymes which inactivate the drug before or after drug entry - e.g. Beta-lactamases)
• Development of a novel metabolic bypass pathway