Self directed antibiotic module Flashcards

Revision

1
Q

How do antibiotics that inhibit protein synthesis do so?

A

Antibiotics that inhibit protein synthesis do so by attaching to bacterial ribosomes, which are structurally different from mammalian ribosomes.

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2
Q

How do we know that most antibiotics that inhibit protein synthesis are bacteriostatic?

A

Usually protein synthesis can resume when the antibiotic is removed, so most of these antibiotics (macrolides, tetracyclines) are bacteriostatic.

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3
Q

What is the definition of bacteriostatic?

A

Inhibits growth but does not kill the bacteria. The bacteria are then killed by white blood cells.

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4
Q

What antibiotics that inhibits protein synthesis is the exception and is not bacteriostatic?

A

THe exception to this is the aminoglycoside group, where the binding of these antibiotics to the ribosome is lethal.

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5
Q

What is the role of Gentamicin (IV)?

A

It binds to ribosomes inhibiting protein synthesis, but bactericidal (kills bacteria).

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6
Q

Why must Gentamicin (IV) be given intravenously?

A

Not absorbed from the gut - must be given intravenously IV (occasionally intramuscularly, IM)

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7
Q

What is Gentamicin (IV) used for?

A

Active mainly against Gram negative aerobic organisms such as coliforms and Pseudomonas aeruginosa) and is used in hospital for treating serious (life-threatening) Gram negative infection.
Excreted in the urine.

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8
Q

How are Erythromycin, clarithromycin and azithromycin excreted from the body?

A

This group of antibiotics is excreted via the liver, biliary tract and into the gut (not excreted in urine).

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9
Q

What are Erythromycin, clarithromycin and azithromycin used for?

A

These antibiotics are lipophilic and pass through cell membranes easily. They are useful for treating certain infections where bacteria “hide” from the host’s immune system by getting into the host cells.
Erythromycin is safe in pregnancy (the others have not been trialled in pregnant women).

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10
Q

What are other antibiotics that inhibit protein synthesis?

A

Clindamycin
Chloramphenicol
Tetracyclines
(all of the above antibiotics are excreted via the liver and biliary system).

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11
Q

What is Clindamycin used for?

A

Used 2nd line to treat serious Staphylococcal and Streptococcal infection, particularly in penicillin-allergic patients.
Also active against the “true” anaerobes (organisms that will not grow in the presence of oxygen).

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12
Q

What is Chloramphenicol used for?

A

Mainly used as topical treatment for eye infections (as eye drops)

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13
Q

What is tetracyclines used for?

A

treating infections caused by bacteria that do not have a proper bacterial cell wall (atypical pneumonia organisms).
Treating some infections (chest, skin) in patients who are penicillin allergic.

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14
Q

How do tetracyclines work?

A

These antibiotics also inhibit bacterial protein synthesis by attaching to ribosomes and are bacteriostatic.
Excreted mainly via the liver and biliary system into the gut.

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15
Q

What type of tetracycline is used in Tayside?

A

Doxycycline (oral) is he tetracycline used in Tayside.

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16
Q

How does selection pressure affect resistance of bacteria?

A

Exposure of bacteria to antibiotics in the environment encourages resistance as small numbers of “resistant mutants” will survive whilst susceptible organisms die off (“survival of the fittest”).

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17
Q

When are selection pressures highest and so the most number of bacteria likely to become resistant?

A

This is particularly likely to happen in the gut of someone who is taking antibiotics, or to bacteria in the hospital environment.
This means that the antibiotics we have are becoming less effective over time and must be used with caution.

18
Q

What allows bacteria to become resistant to an antibiotic?

A

The ability to become resistant to an antibiotic is the result of a change in the bacterial DNA.

19
Q

By what 2 mechanisms does bacterial resistance occur?

A
  1. Genetic mutation
    - “misreading” of the DNA
  2. Transfer of DNA that codes for antibiotic resistance from one bacterium to another by:
    - Transformation
    - Conjugation
    - Transduction
20
Q

How do genetic mutations occur?

A

Bacteria can reproduce rapidly, doubling in population every 20 minutes under ideal conditions.
As a result of this there is a lot of scope for “misreading” of the genetic code.

21
Q

What is the process of transformation?

A

When bacteria die and the cells break apart, “free-floating” DNA released into the surrounding environment may be “scavenged” by other bacteria and incorporated into their DNA. This DNA may contain genes that code for antibiotic resistance and benefit the recipient cell.

22
Q

What is the process of conjugation?

A

Bacteria often contain little “extra” bits of circular DNA called plasmids.
Many plasmids carry genes that confer resistance to antibiotics.
When two bacteria are in close proximity to each other a hollow bridge-like structure, known as a pilus forms between the two cells.
The plasmid replicates and one copy is transferred via the plus to the other bacterium.
This enables a previously susceptible bacterium to acquire the antibiotic resistance.

23
Q

What is the process of transduction?

A

I this process, bacterial DNA is transferred from one bacterium to another inside a virus that infects bacteria. These viruses are called bacteriophages or phages.
When a phage infects a bacterium it takes over the bacteria’s genetic processes to produce more phage.
During this process, bacterial DNA (which may code for antibiotic resistance) may be accidentally incorporated into the new phage DNA.
When the host cell dies and the phages are released from the dead cell, they will then contain DNA from the host bacterium can be transferred to other bacterial cells.

24
Q

How do penicillins work?

A

Inhibits cell wall synthesis, bactericidal.
Safe, very few side effects.
Range from narrow spectrum to broad spectrum
- Broad spectrum = acts on a wide range of bacteria, usually both gram negative and gram positive organisms.
Excreted (rapidly) via kidneys
safe in pregnancy
Any antibiotic with “cillin” in the name is one of the penicillin group.

25
Q

How do Cephalosporins work?

A

Any antibiotic with “ceph” of “cef” in the name is a cephalosporin.
Cephalosporins inhibit cell wall synthesis by preventing cross-linking of peptidoglycan in exactly the same way as penicillins and are bactericidal.
Excreted via the kidneys and urine.
Have few side effects.
Safe in pregnancy.

26
Q

How do Glycopeptides work?

A

Examples are Vancomycin, Teicoplanin (IV).
Cell-wall active antibiotics, but in a slightly different way from the penicillins and cephalosporins.
Bactericidal.
Vancomycin binds to the end of the growing pentapeptide chain during peptidoglycan synthesis, preventing cross-linking and weakening the bacterial wall.
Not absorbed when given orally - have to be administered intravenously (IV).
Glycoproteins are excreted via the kidneys and urine
- toxin level of vancomycin in the blood can build up I patients who have kidney failure, causing further kidney damage.
Only active against organisms with a gram positive cell wall.
No activity against any gram negative organisms.
Vancomycin I not absorbed from the gut, but can be given orally to treat clostridium difficile infection, where it acts topically on the gut lumen.

27
Q

How does Metronidazole (oral, IV) work?

A

Acts by causing strand breakage of bacterial DNA used for:

  • Infection caused by “true” anaerobes (bacteria that will only grow when there is no oxygen in the atmosphere)
  • Some infections caused by protozoa (organisms that are single-celled parasites).
28
Q

How does Trimethoprim (oral) (+/- sulphamethoxazole) work?

A

THe mode of action is that it inhibits bacterial folic acid synthesis.
Paraminobenzoate is converted into dihydropteroate by dihydropteroate synthetase (enzyme) which in inhibited by sulphamethoxazole. This is then converted into dihydrofolate and that is ultimately converted into tetrahydrofolate by dihydrofolate reductase (enzyme) which is inhibited by trimethoprim.

29
Q

How does Fluoroquinolones work?

A

Act by interactin with topoisomerases, enzymes responsible for the supercoiling and uncoiling of bacterial DNA. This interaction means that the bacteria can no longer replicate.
Fluoroquinolones are bactericidal.
The use of these broad spectrum antibiotics is now severely restricted in Tayside in an attempt to reduce the risk of Clostridium difficile gut infection, especially in elderly patients.
These antibiotics are the only antibiotics that can be given orally to treat Pseudomonas infection.
Can get as good blood levels when given orally as when given intravenously.
Excreted in urine.

30
Q

What is the role of Ciprofloxacin (IV, oral)?

A

Used for complicated urinary tract infection and sometimes for urinary tract infection in younger men (<60 years old).

31
Q

What is the role of Levofloxacin (IV only)?

A

Only used for severe community-acquired pneumonia in penicillin-allergic patients.

32
Q

What are the different types of side effects that you can get from antibiotics?

A

General side-effects
Some special side-effects
Penicillin hypersensitivity (“allergy”)

33
Q

What are some general side effects?

A

Many antibiotics cause gastro-intestinal side effects such as nausea and diarrhoea. This may result in failure of oral contraception and another method of contraception is usually required.
Antibiotics kill off the normal gut bacterial flora and allow the overgrowth in the bowel of toxin-producing strains of Clostridium difficile. This causes severe, sometimes fatal, diarrhoea especially in frail, elderly patients.
Giving any antibiotic in sub-optimal doses for prolonged periods encourages bacteria to become “resistant” to the antibiotic.

34
Q
What are the specific side effects of:
Aminoglycosides
Glycopeptides
Tetracyclines
Metronidazole
Quinolones
A

Aminoglycosides
- Gentamicin damages kidneys and causes deafness/dizziness
Glycopeptides
- Vancomycin damages kidneys
- Occasionally causes “red man syndrome” (allergy)
Tetracyclines
- Permanent staining of teeth (and bones) in children <12 years.
Metronidazole
- Interacts with alcohol
Quinolones
- Weakens tendons (tendon rupture)
- May damage joints in children (did so in young animals)
- May cause seizures

35
Q

In a penicillin hypersensitivity wat is the incidence and Type 1 hypersensitivity reaction?

A

Incidence
- Many patients are incorrectly labelled “penicillin-allergic”
- Mild rashes develop in 1-10% of the population.
- True hypersensitivity (below) occurs in <0.05% of treated patients.
Type 1 hypersensitivity reaction
- Itchy rash
- Difficulty breathing, swelling on the mouth/tongue/larynx
- Low blood pressure
- Swelling at the injection site
Such patients must not be given any penicillin-containing antibiotic and cephalosporins should be avoided also.

36
Q

What drugs are safe to use during pregnancy and what drugs are not safe to use?

A

In genera, all the penicillins and cephalosporins are safe to use in pregnancy.
Trimethoprim and metronidazole should be avoided in the first 3 months.
Gentamicin, tetracyclines and fluoroquinolones are not given to pregnant women.

37
Q

What are 3 types of bacterial resistance?

A
  1. Altered antibiotic target binding site
  2. Destruction or inactivation of the antibiotic
  3. Increased efflux
38
Q

What is an altered antibiotic target binding site?

A

A change in bacterial DNA can cuase a change to the gene product which is the target of the antibiotic.
For example, in order to act on the bacterial cell penicillins (such as flucloxacillin) first have to bind to the penicillin binding proteins (PBP), which are present in the bacterial cell wall.
A mutation in the bacterial DNA of Staph. aureus results in the production of an abnormal PBP which no longer binds penicillins sich as flucloxacillin, resulting in these strains becoming resistant to all peniillins and all cephalosporins. These are known as MRSA strains.
Alernatively, the binding site on the bacterial ribosome may alter to prevent attachment of an antibiotic that exerts its effect there.

39
Q

What is the destruction or inactivation of an antibiotic?

A

Many bacteria possess genes which code for enzymes that chemically degrade or inactivate the antibiotic, rendering them ineffective agaist the bacterium.
Some examples of these are the beta-lactamases of whch there are many different types) an cephalosporinases, which specifically target and disrupt the beta-lactam ring of these antibiotics.
One particular concern just now is the production by some Gram negative bacteria of extended spectrum beta-lactamases (ESBLs), enzymes that inactivate almost all the penicillins and cephalosporins.

40
Q

What is increased efflux?

A

Antibiotics enter bacterial cells through channels in the cell wall called porins.
Efflux pups are channels that actively export antibiotics (an other compound) out of the bacterial cell. Genetic change may result in an increase in the rate of efflux, such that the antibiotic is pumped straight back out of the cell before it has time to act.