Antibiotics

Question 1

What are antibiotics?

Answer 1

→ Natural products of fungi and bacteria (so fungi and bacteria naturally produce antibiotics) - soil dwellers

→ Natural antagonism gives organism a selective advantage

→ These natural products kill or inhibit the growth of other microorganisms
→ Most derived from natural products by fermentation, then modified chemically to:
eg - increase pharmacological properties and increase antimicrobial effect

→ Some antibiotics are totally synthetic and not chemically modified - e.g. sulphonamides

Question 2

What do we mean by selective toxicity as a characteristic of antibiotics?

Answer 2

→ We need an antibiotic that can target just the microorganism essentially and not the host
→ Due to the differences in structure and metabolic pathways between host and pathogen

→ Harm microorganisms, not the host
→ Target in microbe, not host (if possible)
→ Difficult for viruses (intracellular), fungi and parasites
→ Variation between microbes

Question 3

What does a loss of flora lead to? What is antibiotic associated colitis?

Answer 3

→ A loss of flora leads to bacterial or pathogen overgrowth

→ Antibiotics damage flora, therefore clostridium difficile is no longer kept in check by this antagonism that is normally there therefore clostridium difficile grows

Question 4

What do we classify antibiotics by?

Answer 4

1. Type of activity
2. Structure
3. Target site for activity

Question 5

What is the difference between bactericidal and bacteriostatic?

Answer 5

Bactericidal:

1. Kill bacteria
2. Used when the host defence mechanisms are impaired
3. Required in endocarditis, kidney infection

Bacteriostatic:

1. Inhibit bacteria
2. Used when the host defence mechanisms are intact
3. Used in many infectious diseases.

Question 6

What is the difference between broad and narrow spectrum antibiotics? Give an example of each

Answer 6

Type of activity when classifying antibiotics

Broad Spectrum Antibiotics:
→ Effective against many types
Example: Cefotaxime

Narrow Spectrum Antibiotics:
→ Effective against very few types
Example: Penicillin G

Question 7

What structural molecular feature can be found in penicillin’s and cephalosporins?

Answer 7

→ Beta-lactam ring
→ Its a square with a double bond oxygen and also nitrogen attached
→ The beta lactam ring is found in most commonly used antibiotics

Question 8

Name a 50S and a 30S protein synthesis inhibitor as an example in bacteria

Answer 8

50S inhibitor:
erythromycin
chloramphenicol (used in eye drops)

30S inhibitor:
Tetracycline
Gentamicin has small therapeutic margin

Question 9

Which group of drugs inhibit DNA Gyrase in bacteria, therefore inhibiting the unwinding of DNA strands?

Answer 9

Quinolones

Question 10

What are some examples of cell wall synthesis inhibitors in bacteria?

Answer 10

1. penicillin’s
2. cephalosporins
3. vancomycin

Question 11

Does gram positive or gram negative bacteria have a large amount of peptidoglycan sitting on the outside of the bacterial membrane?

Answer 11

→ Gram-positive bacteria have a large amount of peptidoglycan

→ In gram-negative bacteria, there is a protective outer membrane, so antibiotics cannot access the peptidoglycan as easily

→ So you can only use certain antibiotics sometimes if they can get through to reach their targets

Question 12

What does it mean when drugs are synergistic ?

Answer 12

The drugs work better in combination than alone

Question 13

When do we use antibiotics? When can they be used inappropriately?

Answer 13

→ Treatment of bacterial infections

→ Prophylaxis - close contacts of transmissible infections

→ Decrease in carriage rates (increase in 80% in outbreaks)
e.g. meningitis
- prevention of infection e.g. tuberculosis

- peri-operative cover for gut surgery
- people with increased susceptibility to infection 	

Inappropriate use - viral sore throats - patient pressure

Question 14

What are the routes of administration for antibiotics?

Answer 14

1. Orally by GP for community infections treatment
2. Serious infections – hospitalisation - systemic treatment
   e.g. i/v rapid delivery, high [blood]
   often unable to take oral – vomiting, unconscious,
   poor gut absorption due to trauma
3. i/v with perivascular collapse (e.g. septicaemia )
4. i/m injection - meningitis case
5. Topical - conjunctivitis, superficial skin infections, burns
6. Antiseptic creams, heavy metal ointments

Question 15

What are the two main types of narrow spectrum penicillin?

Answer 15

1. Basic penicillins e.g. benzylpenicillin (PenG), penicillin V
   → Active against streptococci, pneumococci, meningococci, treopnemes.
   → Most strains of Staphylococcus aureus are resistant. (ie MRSA resistance etc)
2. Anti-staphylococcal penicillins (chemically modified) e.g. flucloxacillin
   → Narrow spectrum, G+ves, beta-lactamase resistant, less potent that PenG
   → Not MRSA

Question 16

What is the difference between the basic penicillin’s Pen G and Pen V?

Answer 16

Pen G benzlypenicillin (G= gold standard):
→ not acid stable so you cannot give Pen G orally
→ therefore i/v or i/m good for some G-ves as well as G+ves

Pen V phenoxymethlypenicillin
→ oral (more acid stable than penG)
→ less active v G-ves, but same activity v G+ves as PenG

Question 17

What are some other examples of broader/extended spectrum penicillin’s?

Answer 17

e.g. ampicillin

→ Spectrum of activity is similar to basic penicillins but also includes some Gram-negative organisms and also enterococci

Anti-pseudomonal penicillins:
→ e.g. piperacillin - works against pseudomonas infections whereas other penicillins would not
→ extended spectrum beta-lactam antibiotic
also G+ve, G-ve, anaerobes

→ Beta-lactam/beta-lactamase inhibitor combinations
e.g. co-amoxiclav (Augmentin)

→ Spectrum like amoxicillin plus activity against some gram-negatives and Staph aureus

Question 18

What are some examples of Cephalosporins?

Answer 18

There are many of these agents often classified by generation. Some examples include:

1. Cefalexin:
   An oral agent primarily used to treat UTIs
2. Cefuroxime:
   A parenteral 2nd generation agent with good activity against many Gram-positive and Gram-negative organisms
3. Cefotaxime:
   A parenteral 3rd generation agent with greater activity against many Gram- negative and retaining anti-Gram-positive activity
4. Ceftazidime:
   A parenteral 3rd generation agent with a spectrum of activity extended to include Pseudomonas aeruginosa

Question 19

What does parenteral mean?

Answer 19

Drug cannot be given orally ie intravenously etc

Question 20

What are some examples of aminoglycosides and what do we know about them?

Answer 20

→ This group includes gentamicin, amikacin and streptomycin
→ These agents cannot be absorbed from the gut and must be given parenterally
→ They are active predominantly against Gram-ve bacteria including Pseudomonas aeruginosa
→ These agents are nephrotoxic and ototoxic and serum levels must be monitored

Question 21

What is an example of a macrolide?
What is it used to treat?

Answer 21

e.g. erythromycin (good as alternative to penicillin as people are allergic)
→ Used to treat Gram-positive infections esp. in those allergic to beta-lactams
→ Also active against:
Mycoplasma pneumoniae and Legionella pneumophila

Question 22

What are some examples of glycopeptides?

Answer 22

→ Includes vancomycin and teicoplanin
→ Active only against Gram-positive organisms
→ Parenteral only
→ Usually reserved for situation when other agents cannot be used e.g. against MRSA

Question 23

What are some examples of tetracyclines?

Answer 23

→ Includes oxytetracycline, doxycycline
→ Broad spectrum
→ Used mainly for treating:
Chlamydia, Mycoplasma pneumoniae, Acne

Question 24

What are some examples of quinolones? (inhibit DNA gyrase activity in bacteria)

Answer 24

→ Includes ciprofloxaxin, moxifloxacin
→ Older drugs such as ciprofloxacin active mostly against Gram-negatives
→ Useful for complicated UTIs and gastrointestinal infections
→ Newer agents have better anti-Gram-positive activity
→ Useful for some respiratory tract infections

Question 25

Other agents as extra info

Answer 25

1. Trimethoprim – useful for UTIs. Combined with sulphamethoxazole as co-trimoxazole
2. Metronidazole – active against anaerobic bacteria (and some parasites) (generates free radicals?)
3. Chloramphenicol – broad spectrum. Used rarely systemically because of side-effects. Commonly used topically for eye infections
4. Fusidic acid – narrow spectrum, used in combination to treat Staphylococcal infections only.
5. Nitrofurantoin – useful for UTIs. (generates free radicals)
6. Linezolid – an oxazolidinone. The newest antibiotic reserve for multi-resistant Gram-positive infections
7. Daptomycin – lipopeptide with similar spectrum of activity to vancomycin
8. Tigecycline – glycylcycline (related to tetracyclines) – reserved for use against multiply-resistant Gram-positive and Gram-negative bacteria