L39 & 40. Using Antibiotics

Question 1

What is the relationship between antibiotic usage and antibiotic resistance?

Answer 1

The higher the usage of antibiotics, the higher the incidence and development of antibiotic resistant infections

Question 2

What considerations must be made when choosing antibiotic treatments? [5]

Answer 2

1. Making the right clinical diagnosis
2. Make the right microbiological diagnosis
3. Checking in vitro susceptibility
4. Host factors (eg. immunosuppression, pregnancy)
5. Properties of the Abx (eg. toxicity, kinetics, administration, distribution etc)

Question 3

What is the MIC?

Answer 3

The Minimum Inhibitory Concentration: is the lowest concentration of the antibiotic required to inhibit bacterial growth in culture: gives an indication of susceptibility to the antibiotic

Question 4

Describe the disc susceptibility test

Answer 4

A disc impregnated with antibiotics is plated onto a disc. The antibiotic is allowed to diffuse through the agar (concentration dependent). Susceptible bacteria grow on the plate with a Zone of Inhibition that is proportional to the MIC.
The Disk Diameter break points: determines the relationship between the disc diameter and the MIC

Question 5

Describe the E-test strip

Answer 5

A modified method of the disc susceptibility test that uses a strip of exponentially graded antibiotic concentrations placed onto a plate that fives an MIC directly off it.

Question 6

What specific considerations about the antimicrobial agent should be made? [6]

Answer 6

1. Spectrum of action
2. Clinical efficacy of the antibiotic (whether it works in vivo)
3. Route of administration (and excretion)
4. Pharmacokinetics/dynamics
5. Availability
6. Cost

Question 7

What are the three most common prescribing errors when it comes to antibiotics?

Answer 7

1. Prescribing them when they aren’t needed (Eg. viral infections)
2. Prescribing the wrong antibiotic
3. Using the correct antibiotic but with the incorrect dose, course, route, patient

Question 8

What is Empirical or Best Guess Antimicrobial therapy? Why do we use it?
- What considerations should be made when using it?

Answer 8

There are some infectious diseases that we don’t know the causative and susceptibility of the organism and not treating leads to complications and symptomatic suffering.

Consider:
Whether Abx is needed, safety and whether there is time to wait for a diagnosis, likely causative agents, susceptibility and whether evidence exists that treatment will help

Question 9

Why do we use antibiotics in combination?

Answer 9

As a temporary measure (while waiting for more information)
To delay emergence of resistance
To treat mixed infections
Reduce toxicity
Achieve synergistic effects

Question 10

What is an example of using antibiotic combinations to decrease the emergence of resistance?

Answer 10

TB therapy: normally start with administering 4 frontline drugs because if one or two are resistant then another 2 exist to kill the bacteria before the resistant bacteria can spread.
Important to TB infections because a slow replication cycle means a higher likelihood for mutations (and resistance) to occur.

Question 11

What are the three types of antibiotic combination interactions?

Answer 11

1. Indifference: an additive effect that is the same as using higher concentrations of either drug [A + B = A + A = B + B]
2. Antagonism: where they are worse than one alone
3. Synergy: where the combinations provide a supra-additive effect

Question 12

What are the mechanisms of synergy?

Answer 12

1. Blockage of the sequential steps of a metabolic pathway (anything that gets through the first step is stopped by the next one)
2. Inhibition of enzymatic degradation (eg. co-amoxyclav)
3. Enhancing antimicrobial uptake by the cell wall

Question 13

What is an example of synergistic antibiotics?

Answer 13

Penicillin G and Streptomycin
Amoxycillin and Covulanic acid

Folic acid synthesis is targeted by a combination of sulphonamides and trimethoprim

Question 14

What are the mechanisms of antagonism?

Answer 14

1. Inhibiting bactericidal activity by a bacteriostatic agent (tetracycline and penicillin)
2. Inducing enzymatic degradation of one agent by another agent
3. Competition for binding to the same target
4. Inhibition of the target

Question 15

What are examples of antagonism?

Answer 15

Ampicillin + piperacillin (ampicillin can be resistant and induces the B-lactamase too be produced and so the pipercillin which was susceptible is rendered useless because the beta lactamase degrades it)

Question 16

Why is treatment of meningitis by penicillin + tetracycline not useful?

Answer 16

Tetracycline is bacteriostatic and stops the growth of all bacteria meaning that synthesis of the PG doesn’t occur anymore. Thus the target for penicillin isn’t available anymore and so it doesn’t work at all. Such that the bacteria are now resistant and protected against penicillin

Question 17

What are Jawetz’s Laws?

Answer 17

A rough guide for combination interactions:

1. Bacteriostatic + Bacteriostatic = Additive or Indifferent
2. Bacteriostatic + Bactericidal = Antagonistic
3. Bactericidal + Bactericidal = Synergistic

Question 18

How does the co-amoxyclav combination work?

Answer 18

Clavulanic acid + amoxycillin
Clauvulanic acid is a beta lactamase inhibitor which means the beta lactamases is degraded by the clavulanic acid meaning the amoxycillin is able to work (expands the spectrum).