Antibiotics

Question 1

Antibiotics - define

Answer 1

Natural products of fungi and bacteria - soil dwellers

- natural antagonism and selective advantage
 	- kill or inhibit the growth of other microorganisms

Question 2

Antibiotics - derived from

Answer 2

most derived from natural products by fermentation,
then modified chemically :- ↑ pharmacological properties
↑ antimicrobial effect

Some totally synthetic - e.g. sulphonamides

Question 3

Principles of Antibiotics as Therapeutic Agents - selective toxicity due to what and effect

Answer 3

Selective Toxicity
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 4

Principles of Antibiotics as Therapeutic Agents - Therapeutic Margin = explain

Answer 4

active dose (MIC) versus toxic effect
narrow for toxic drugs - e.g. aminoglycosides, vancomycin
ototoxic, nephrotoxic

Question 5

Microbial antagonism - purpose

Answer 5

Maintains flora - complex interactions
Competition between flora

Limits growth of competitors and PATHOGENS

Question 6

Effect of loss of flora on bac/pathogen

Answer 6

Loss of flora → bacterial or pathogen overgrowth

e.g. Antibiotic Associated Colitis :
(clindamycin, broad-spectrum lactams, fluoroquinolones)
- pseudomembranous colitis

	Clostridium difficile  (part of normal flora of 3% of population)

Question 7

Antibiotic Associated Colitis - effect on body

Answer 7

Ulcerations – inflammation
Severe diarrhoea
Serious hospital cross-infection risks

Question 8

Pseudomembranous colitis effect on c. difficile

Answer 8

Pseudomembranous colitis

Clostridium difficile
overgrowth

Question 9

Antibiotic + immunity =

Answer 9

Antibiotic + immunity → bacterial clearance

Question 10

Antibiotics classified by

Answer 10

Classified by:-

Type of activity

Structure

Target site for activity

Question 11

Bactericidal AB - effect, use

Answer 11

Bactericidal:

Kill bacteria

Used when the host defense mechanisms are impaired

Required in endocarditis

Question 12

Bacteriostatic AB - effect, use

Answer 12

Bacteriostatic:

Inhibit bacteria

Used when the host defense mechanisms are intact

Used in many infectious diseases

Question 13

Spectrum of Activity - describe for AB

Answer 13

Broad Spectrum Antibiotics:
Effective against many types
Example: Cefotaxime

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

Question 14

ABs in relation to bac enzymes

Answer 14

Antibiotics are often structural mimics

of natural substrates for bacterial enzymes

Question 15

Protein synthesis inhibitors describe action with examples at each step

Answer 15

Binding fmet t-RNA
Initiation complex formation

• Aminoglycosides
  e. g. streptomycin = bind to 30S ribosome

Translocation of fmet t-RNA
to P site

• e.g. genatmicin (aminoglycoside) = bind to 30S ribosome

Competition with new
Aminoacyl t-RNA
at the A site

• e.g. tetracycline (aminoglycoside) = bind to 30S ribosome

Blocks formation of
peptide bond
peptidyl transferase

• e.g. chloramphenicol (aminoglycoside) = bind to 50S ribosome

Block translocation of
peptidyl t-RNA

• e.g. erythromycin (macrolide) and fusific acid = bind to 50S ribosome

Question 16

When do we use antibiotics ?

Answer 16

Treatment of bacterial infections

Prophylaxis - close contacts of transmissible infections
carriage rates (↑ ~80% in outbreaks)
e.g. meningitis
- prevention of infection e.g. tuberculosis

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

Question 17

Describe inappropriate use of ABs

Answer 17

Inappropriate use - viral sore throats - patient pressure

Question 18

Route of Administration of ABs for serious infection

Answer 18

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

?? i/v  with perivascular collapse (e.g. septicaemia )
	i/m injection  -   meningitis case

Question 19

Route of Administration of ABs for topical infection

Answer 19

Topical - conjunctivitis, superficial skin infections, burns
antiseptic creams, heavy metal ointments

Question 20

Dose of antibacterial

MIC depends on what

Answer 20

This will depend upon the age, weight, renal and liver function of the patient and the severity of infection
Depend on the susceptibility of the organism
Will also depend upon properties of the antibiotic i.e. enough to give a concentration higher than the MIC (minimum inhibitory concentration)
! at the site of infection

Question 21

Antibiotic Combinations - used when and effects

Answer 21

BEFORE an organism identified in life-threatening infections
e.g. endocarditis, septicaemia

Polymicrobial infections e.g. abscess, G.I. perforation
anaerobes and aerobes

Less toxic doses of an individual drug possible

Synergy e.g. penicillin and gentamicin
Co-trimoxazole (sulphonamides + trimethoprim)

reduce antibiotic resistance e.g. Tuberculosis

Question 22

Basic penicillins - example and active against what

Answer 22

Basic penicillins e.g. benzylpenicillin(PenG), penicillin V
Active against streptococci, pneumococci, meningococci, treopnemes.
Most strains of Staphylococcus aureus are resistant.

Question 23

Anti-staphylococcal penicillins - example and active against what

Answer 23

Anti-staphylococcal penicillins e.g. flucloxacillin
narrow spectrum, G+ves, beta-lactamase resistant, less potent that PenG
Not MRSA

Question 24

benzlypenicillin - use

Answer 24

Pen G benzlypenicillin (G= gold standard);

not acid stable ∴ i/v or i/m good for some G-ves as well as G+ves

Question 25

phenoxymethlypenicillin - use

Answer 25

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

Question 26

Broader spectrum penicillins - example and active against what

Answer 26

Broader spectrum penicillins e.g. ampicillin

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

Question 27

Anti-pseudomonal penicillins - example and active against what

Answer 27

Anti-pseudomonal penicillins e.g. piperacillin
extended spectrum beta-lactam antibiotic
also G+ve, G-ve, anaerobes

Question 28

Beta-lactam/beta-lactamase inhibitor combinations - example and active against what

Answer 28

eta-lactam/beta-lactamase inhibitor combinations
e.g. co-amoxiclav (Augmentin)
Spectrum like amoxicillin plus activity against some Gram-negatives and Staph aureus

Question 29

cefalexin - use

Answer 29

cefalexin An oral agent primarily used to treat UTIs

Question 30

cefuroxime - use

Answer 30

cefuroxime A parenteral 2nd generation agent with good activity against many Gram-positive and Gram-negative organisms

Question 31

cefotaxime - use

Answer 31

efotaxime A parenteral 3rd generation agent with greater activity against many Gram- negative and retaining anti-Gram-positive activity

Question 32

Ceftazidime - use

Answer 32

Ceftazidime A parenteral 3rd generation agent with a spectrum of activity extended to include Pseudomonas aeruginosa

Question 33

Aminoglycosides - give examples

Answer 33

This group includes gentamicin, amikacin and streptomycin

Question 34

Aminoglycosides - characteristics

Answer 34

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 35

Macrolides - example and used for

Answer 35

e.g. erythromycin

Used to treat Gram-positive infections esp. in those allergic to beta-lactams

Also active against
Mycoplasma pneumoniae and
Legionella pneumophila

Question 36

Glycopeptides - examples and used for

Answer 36

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 37

Tetracyclines - examples and used for

Answer 37

Includes oxytetracycline, doxycycline
Broad spectrum

Used mainly for treating:

Chlamydia
Mycoplasma pneumoniae
Acne

Question 38

Quinolones - examples and used for

Answer 38

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 39

Trimethoprim – used for

Answer 39

Trimethoprim – useful for UTIs. Combined with sulphamethoxazole as co-trimoxazole

Question 40

Metronidazole – used for

Answer 40

Metronidazole – active against anaerobic bacteria (and some parasites)

Question 41

Chloramphenicol – used for

Answer 41

Chloramphenicol – broad spectrum.

Used rarely systemically because of side-effects.

Commonly used topically for eye infections

Question 42

Fusidic acid – used for

Answer 42

Fusidic acid – narrow spectrum, used in combination to treat Staphylococcal infections only.

Question 43

Nitrofurantoin - used for

Answer 43

Nitrofurantoin – useful for UTIs.

Question 44

Linezolid - used for

Answer 44

Linezolid – an oxazolidinone. The newest antibiotic reserve for multi-resistant Gram-positive infections

Question 45

Daptomycin - used for

Answer 45

Daptomycin – lipopeptide with similar spectrum of activity to vancomycin

Question 46

Tigecycline - used for

Answer 46

Tigecycline – glycylcycline (related to tetracyclines) – reserved for use against multiply-resistant Gram-positive and Gram-negative bacteria