Antibiotics

Question 1

What is the approval and regulation of animal antibiotics like?

Answer 1

FDA reviews and approves animal medicines using the same standards and processes as those for human medicine

Question 2

What is mostly responsible for the risk of antibiotic resistance? How does this compare in animals?

Answer 2

human healthcare use —> overuse and misuse of antibiotics

risk of antibiotic use in animals is extremely low compared to uses in human healthcare settings

Question 3

What are the 2 major functions of antibiotics?

Answer 3

1. bactericidal - kills bacteria
2. bacteriostatic - inhibit the growth and proliferation of bacteria, allowing the animal’s immune system to more effectively fight the bacterial infection

Question 4

What is an antibacterial spectrum? What are the 2 types?

Answer 4

range of activity of an antibiotic

1. BROAD SPECTRUM - antibiotic can inhibit a wide range of Gram + and Gram - bacteria (Carbapenems, 3-4 gen Cephalosporins)
2. NARROW SPECTRUM - antibiotic is active only against a limited number of bacteria (Penicillin, 1-2 gen Cephalosporins)

Question 5

How do Gram-positive and Gram-negative bacteria compare?

Answer 5

POSITIVE = stains purple due to thick peptidoglycan layers

NEGATIVE = stains pink due to thin peptidoglycan layer and LPS

Question 6

What 4 characteristics should influence selection of antimicrobial drugs?

Answer 6

1. spectrum of activity
2. PK and PD - minimal inhibitory concentration
3. potential side effects
4. drug sensitivity of bacteria

Question 7

What antibiotic is Mycoplasma resistant to? Why?

Answer 7

Penicillin —> does not contain/produce penicillin-binding protein

Question 8

What questions should be considered with selecting appropriate antimicrobial agents?

Answer 8

• Is an antimicrobial agent required? Is there an infection that will respond to treatment?
• Where is the infection? What are the drug access problems to overcome?
• Which pathogen(s) are usually found at the location of infection?
• Which antimicrobial agent has the necessary PK to get to the location and get there at a concentration above the minimal inhibitory concentration so that MIC is below the breakpoint?
• What dose and route are necessary to achieve the desired effect?
• How long should treatment be for?

Question 9

What antimicrobial agents are preferred in immunocompromised patients?

Answer 9

bactericidal —> immune system may not be functional enough to overcome even a deactivated bacteria

Question 10

What is important to consider in antibiotic treatments for food-producing animals?

Answer 10

residues in milk and meat requires withdrawal times before slaughter

Question 11

What governs the dosing intervals? Pre-slaughter withdrawal times?

Answer 11

drug plasma concentration

tissue residence times

Question 12

What are 5 mechanisms that bacteria may manifest resistance?

Answer 12

1. bacteria may produce enzymes that deactivate the drug
2. permeability to or uptake of drug may be decreased
3. transport out of the cell (MDR1) may be increased
4. alteration of the drug receptor or binding site may result in reducing the affinity
5. may develop alternative metabolic/synthetic pathways to bypass or repair effects of drug

Question 13

What are 4 mechanisms by which bacteria develop resistance?

Answer 13

1. MUTATION: bacteria randomly undergoes chromosomal mutations
2. CONJUGATION: genetic material is transerred from cell to cell via resistance transfer factor (RIF); infections drug resistance
3. TRANSDUCTION: transferring drug resistant gene by bacteriophages
4. TRANSFORMATION: incorporation of naked DNA encoding drug resistance

Question 14

Bacterial structure:

Answer 14

PROKARYOTIC - single-celled, lacking organelles and nucleus

Question 15

What are the 6 mechanisms of actions of different antibacterial cells?

Answer 15

1. block production of peptidoglycan, inhibiting cell wall synthesis (select toxicity - no side effects to host cells because they lack peptidoglycan)
2. binds to 70S ribosome, blocking protein synthesis
3. interferes/alters bacterial cell membrane or LPS in Gram - outer membrane to
4. inhibits DNA synthesis, blocking cell replication and transcription
5. competes with bacterial metabolic enzymes, stopping synthesis of product (antimetabolite)
6. interrupts ATP synthesis to reduce ATP production

Question 16

Antibiotics and mechanism of action:

Answer 16

Question 17

What are the 3 targets of antibiotics that target cell wall biosynthesis? What drugs are in each category?

Answer 17

1. transpeptidase/penicillin-binding proteins (PBPs) - β-lactams (Penicillins, Cephalosporins, Carbapenems, Monobactams)
2. peptidoglycan subunits - glycopeptides (Vancomycin)
3. peptidoglycan subunit transport - Bacitracin

Question 18

How was Penicillin discovered?

Answer 18

Alexander Fleming was doing research on Staphylococcus and left a plate on his bench over holiday - when he came back a fungus (Penicillin rubens) was growing on the plate and prevented Staphylococcus from growing near it

Question 19

What is structurally the same in all Penicillins?

Answer 19

β-lactam, a four-atom ring
(structure defines function)

Question 20

What are the 2 divisions of Penicillins based on spectrum?

Answer 20

NARROW SPECTRUM:
- natural penicillis: Penicillin G and V
- very narrow spectrum/anti-Staphylococcal: Methicillin, Oxacillin, Cloxacillin

BROAD SPECTRUM:
- extended spectrum: Ampicillin, Amoxicillin
- anti-pseudomonal: Carbenicillin, Ticarcillin, Piperacillin

Question 21

What 2 enzymes are responsible for the development of Penicillin resistance?

Answer 21

1. penicillinase - inactivates Penicillin
2. β-lactamase - produced by almost all Gram-negative bacteria and hydrolyzed the β-lactam ring of Penicillins and Cephalosporins

Question 22

What are the 3 β-lactamase inhibitors used as potentiated penicillins?

Answer 22

1. clavulanic acid (Amox or Ticar)
2. sulbactam (Amp)
3. Tazobactam

Question 23

What are the 2 natural penicillins? What are their therapeutic uses? What bacteria do they work against?

Answer 23

1. Penicillin G - treats infections in all species
2. Penicillin V - used INFREQUENTLY for long-term oral therapy in dogs, cats, and horses

Gram + non-penicillinase-producing pathogens

Question 24

What are the 3 penicillin-resistant penicillins? What are their therapeutic uses? What bacteria do they work against?

Answer 24

1. Methicillin
2. Oxacillin
3. Cloxacillin

treats against severe Staph infections, but less effective against Strep than natural penicillins

Gram +

Question 25

What are the main 2 groups of broad-spectrum penicillins? What are their therapeutic uses? What bacteria do they work against?

Answer 25

1. Ampicillin, Amoxicillin - treats infection in all species
2. Carbenicillin, Ticarcillin, Piperacillin - treat ear and skin infections in dogs caused by Pseudomonas spp.

Gram + and Gram -; not penicillinase stable

Question 26

Which penicillins are well-absorbed orally? Why?

Answer 26

• Penicillin V
• Ampicillin
• Amoxicillin
• Oxacillin
• Cloxacillin
• Carbenicillin

acid-stable against gastric acid

Question 27

Which penicillins are poorly absorbed orally? Why?

Answer 27

• Penicillin G
• Methicillin
• Ticarcillin

broken down by gastric HCl

Question 28

What are the main 2 causes of penicillin resistance?

Answer 28

1. inactivation of penicillins by penicillinases
2. not binding to penicillin-binding proteins (PBPs)

Question 29

What is the most common adverse reaction in horses taking penicillins? Potassium penicillin? Procain G penicillin?

Answer 29

allergic reactions

cardiac arrhythmia (IV) in all species and diarrhea in horses

spontaneous abortion in cows

Question 30

When is Procaine G penicillin contraindicated?

Answer 30

birds, snakes, turtles, guinea pigs, chinchillas, or racehorses due to CNS effects