Antibiotics

Question 1

What are the main implications for the use of antibiotics?

Answer 1

1. Prophylactic treatment in an individual who is at risk of an infection, e.g. Surgery, immunosuppression.
2. Treatment of an ongoing, active infection which will significantly benefit the condition, e.g. Life threatening.

Question 2

How might previously susceptible bacterial cell acquire resistance to a particular antibiotic?

Answer 2

1. Verticals transmission, i.e. Through DNA replication during meiosis.
2. Horizontal gene transfers - conjugation for the transfer of a plasmid containing a resistance gene, transduction of genetic material using phagosomes, transformation through the uptake of free DNA into the cell.
3. Random DNA mutation - e.g. In a PBP stopping the binding of beta-lactams.

Question 3

Give some examples of mechanisms by which a bacteria can resist the effect of antibiotics.

Answer 3

1. Mutations of the target protein - e.g. MRSA
2. Development of an enzyme which breaks down the drug - e.g. beta-lactamase
3. Increased efflux or decreased influx of the drug - e.g. Tetracyclins
4. Creation of an alternative metabolic pathway to bypass the inhibited step - e.g. Sulphonamides

Question 4

What is the MIC of an antibiotic and what is the use?

Answer 4

MIC is the minimum concentration of drug required to inhibit the growth of bacterial cells. The MIC is used to determine the sensitivity of strains to given antibiotics. The smaller the concentration, the more sensitive the bacteria to the drug.

Question 5

List the major adverse drug reactions associated with antibiotic use.

Answer 5

1. Hypersensitivity - allergy, i.e. Urticaria, rash, anaphylaxis
2. Drug interactions - inhibitors and inducers the CYP450 enzyme system (rifampacin inducer, sulphonamides/ciprofloxacin/erythromycin inhibitors)
3. Side effects - antibiotic side effect most commonly affect the GI system. They can include diarrhoea, nausea, vomiting, bloating, abdominal pain, loss of appetite.

Question 6

What two approaches can be used to limit the emergence of drug resistance?

Answer 6

1. Antimicrobial stewardship - a programme ensuring the correct use of antibiotics in terms of timing, dosage, length and route of administration.
2. Infection control - limiting the spread of an infection to reduce the need for antibiotics and reducing the spread of resistant strains to patients.

Question 7

What two antibiotics need therapeutic drug monitoring?

Answer 7

Vancomycin, gentamycin

Question 8

Why do some antibiotics need therapeutic drug monitoring schemes?

Answer 8

Certain antibiotics, such as gentamycin and vancomycin, require therapeutic drug monitoring because they have a low therapeutic index/narrow window. This means that if their concentration is too high, they can become toxic, whereas if it falls too low they are not effective.

Question 9

What is the therapeutic index?

Answer 9

The TI is a measure of the therapeutic window, defined as the LD50/EC50, or the dose which is lethal in 50% of the popoulation (maximal lethal dose) to the dose which is effective in 50% of the population (minimum effective dose). A large window means the dose of the drug can vary widely and be minimally toxic and effective, while a narrow range means the drug only works and is not toxic in a narrow range of concentrations.

Question 10

What is meant by concentration-dependant killing for antibiotics?

Answer 10

Concentration dependant killing is a pharmacodynamic factor relating to the interaction of the drug and the bacteria. Such antibiotics kill bacteria more effectively at increasing concentrations (e.g. 10x MIC), however they do not improve with increased lengths of dose. They show a good post-antibiotic effect.

Question 11

What is meant by time-dependant killing for antibiotics?

Answer 11

Time-dependant killing is a pharmacodynamic factor relating to the interaction of the drug and the bacteria. Such antibiotics kill bacteria more effectively when given for longer periods of time, however do not improve when given at higher concentrations. These antibiotics have little to no post-antibiotic effect.

Question 12

What is the difference between the pharmacokinetic parameters Cmax:MIC and t>MIC?

Answer 12

Cmax:MIC is the difference in drug concentration between the peak concentration and the MIC. A large value indicates that the drug has a range of concentrations in which it is effective, most relevant to concentration-depending killing.

t>MIC is the time the concentration of a drug remains above the MIC, most relevant to time-dependant killing. The greater the value, the longer the drug is effective.