Intro to antimicrobials

Question 1

What are the roles of antibiotics?

Answer 1

• Reduce the effects on infection (helping host mechanisms clear it)
• Directly clear infection
• used prophylactically when infection risk is high

Question 2

What is the definition of antibiotics?

Answer 2

Low molecular weight microbial metabolites which kill/ inhibit growth of susceptible bacteria

Question 3

What is the role of the magic bullet and what features does it target?

Answer 3

• To target unique features of a pathogen

- e.g. ribosome structures and bacterial wall unique compounds (TLR agonist)

Question 4

Which out of bacteria, viruses or fungi are easiest to target?

Answer 4

Bacteria

- viruses use patients own biology

Question 5

What is a negative result of the effect of antimicrobials on bacterial cells?

Answer 5

Some bacterial pathogens release components when the cell is lysed -> these can be toxic e.g. gram negative cell release lipid A which causes sepsis

Question 6

What are the differences between bacteria which impact on drug action?

Answer 6

• Gram -/+
• Acid fast (grouped with gram +)
• Mycoplasma (no cell wall)
• Aerobic activity

Question 7

Name other control techniques you can use other than antibiotics

Answer 7

• Biosecurity
• Vaccinations
• Isolation/ removal of infected animals

Question 8

What is the difference between Bactericidal and bacteriostatic drugs?
Give examples

Answer 8

Bactericidal= kills the organism (penicillins/ cephlasporins)
Bacteriostatic= drugs that temporarily inhibit the growth of an organism (it is reversible if removed) (tetracylines, choramphenicol)

Question 9

What is the significance of Beta lactams bacteristatic antibiotics?

Answer 9

If you use Beta lactams and bacteristatic antibiotics in combination with each other then you will not kill the bacteria. For beta lactams to be effective the bacteria HAS to be growing. If you use it alongside a baceriostatic antibiotic then once then therapy is removed the bacteria will start growing again.

Question 10

When would you use bacteriocidial antibiotics?

Answer 10

• when the infection CANNOT be controlled or destroyed by the host
• May bee because of site or infection (endocarditis) or if the host is immune suppressed (FELV)

Question 11

What does MIC and MBC stand for and what is their significance?

Answer 11

MIC: minimum inhibitory concentration (amount needed at infection site to achieve bacterial inhibition)
MBC: minimum bactericidal concentration (concentration required at infection site to kill the bacteria)

Question 12

What impacts on MIC and MBC?

Answer 12

• MIC and MBC is more achievable in some sites rather than others
• Pharmacological properties where antimicrobials distribute
  -How they are eliminated from the host
  -Bacterial resistance:
  the bacterial mechanisms can increase the MBC and MIC above certain points making them unachievable clinically

Question 13

What is the significance of bacterial resistance on the success of antimicrobial therapy?

Answer 13

• Bacterial mechanisms can increase MIC and MBC above a clinically achievable threshold

Question 14

What is needed for an antibmicrobial agent ot be effective?

Answer 14

• It must be distribute to the right site at a adequate MIC/ MBC
• It must come into contact with the organisms

Question 15

What can hinder the antibmicrobials reaching the infection site?

Answer 15

• Milk proteins can bind some antibiotics
• Local pH can reduce disassoiation of some antibiotics and reduce distribution
• Poor blood supply/ good epithelial barriers reduce drug access
• Abscess formation (pus)
• Foreign bodies
• Oedema fluid

Question 16

Give examples of patient specific factors that can affect drug access?

Answer 16

• Meningitis may reduce the BBB allowing entry of drugs which would normally be blocked

Question 17

Which group of animals can you NOT give PO antibiotics to?

Answer 17

Ruminants

Question 18

Describe time dependent activity and concentration dependent activity in terms of dose frequency

Answer 18

• Time dependent: time the serum conc exceeds the MIC, increasing serum conc above MIC will not increase killing (Beta lactams, tetracylines, chloramphenicol)
• Concentration dependant: killing increases with increased concentration, required high concentration at binding site to be effective
• Not always beneficial to maintain this level between doses (flouroquinolones, aminoglycosides)

Question 19

How does drug solubility affect cell penetration?

Answer 19

• Highly lipid soluble drugs can penetrate cells and have a large vol distribution (tetracylines, quinolones)
• water soluble are stuck in the blood/ extracellular fluids (beta lactams, aminoglycosides)

Question 20

Describe host barriers that effect cell penetrations and removal

Answer 20

• BBB= poor penetration of antibiotics so high doses needed
• Areas/ pathologies can have poor perfusion
• Metabolism: many antibiotics metabolised by liver
• Excretion: kidneys may excrete antibiotics leading to high level in the urine - this is a good thing for UTIs but not systemic infections

Question 21

What is MRL?

Answer 21

Maximum Residue Levels: restrictions on use of antimicrobials in food producing animals

• Residues can get into food
• Withdrawal times

Question 22

What factors affect MRL?

Answer 22

• Drug persistence profiles
• Drug dosing schedule
• Route of dose

Question 23

What is the main side effect of Aminoglycosides?

Answer 23

Nephrotoxicity

Question 24

What is the main side effect of Quinolones?

Answer 24

Tendon damage

Question 25

What is the main effecct of Rifampicins?

Answer 25

Liver problems

Question 26

Describe the metabolism of Rifampicin?

Answer 26

• Metabolised by the liver where it induces P450 pathway, promotes the up regulation of hepatic cytochrome P450 enzymes.
• It increases the rate of metabolism of many other drugs normally cleared by the liver