Lecture 8

Question 1

Antimicrobials are and the different types

Answer 1

Chemicals that inhibit the growth or kill microorganisms
Antimicrobial is a generic term that includes:
Antibiotics – specific to BACTERIA
Antivirals – specific to VIRUSES
Antifungals – specific to FUNGI

Question 2

Mechanism of action of antibiotics

Answer 2

Antibiotics act on or alter 1 of 5 different locations in the bacteria cell:
Cell wall
Cell membrane
Ribosomes
Metabolic enzymes
DNA replication

Question 3

Drugs that inhibit cell wall synthesis

Answer 3

Gram positive cell wall is rigid
Prevents cell from swelling until it bursts
Certain antibiotics block proper cell wall synthesis
Only work on growing cells
Cell wall is structurally copromised so cannot prevent swelling
Kills bacteria that are in the process of growing

Question 4

Beta lactam antibiotics

Answer 4

Drug class that affects cell wall formation
Two major subclasses
PENICILLINS
CEPHALOSPORINS
All drugs contain a beta-lactam ring
Beta-lactam ring binds to and blocks the enzyme transpeptidase from functioning
Transpeptidase produces the peptide cross-links between the peptidoglycan layers
Result: Gram positive cell wall that lacks strength

Question 5

Resistance to Beta-Lactam Antibiotics

Answer 5

Most important mechanism of beta-lactam resistance is bacterial enzyme called beta-lactamase
Enzyme cleaves the beta-lactam ring so functional group is damaged
drug can no longer bind to transpeptidase
Gene for this enzyme is found on plasmids
Spread to progeny and other bacteria

Question 6

Drugs That Disrupt The Cell Membrane

Answer 6

Certain antibiotics insert into the plasma membranes
Effects:
Act like detergents and disrupt lipid layers
Act like channels or pores - allow cytoplasm to leak from the cell
Can increase the ability of other antibiotic drugs to enter into the cell
Kills bacteria
Drug classes: polymixins, aminoglycosides

Question 7

Drugs That Block Ribosome Function

Answer 7

Antibiotics can block protein synthesis by:
Binding to the ribosome and blocking its function
Binding to the tRNA so amino acids cannot be transported to the ribosome
Bacteria either stops growing or dies
Classes of drug: aminoglycosides, macrolides, lincosamides, tetracyclines, chloramphenicol, florfenicol
Aminoglycoside Mechanism of Action
Causes mRNA to be misread

Question 8

Drugs That Block Metabolic Enzymes

Answer 8

Some antibiotics bind to the active site of critical metabolic enzymes and block function
Other antibiotics bind to critical enzyme cofactors, coenzymes or substrates
compounds are no longer available for metabolism
Stops growth, not as good for killing
Drug classes: sulphonamides, anti-metabolites

Question 9

Drugs That Block DNA Synthesis

Answer 9

Antibiotics bind to the DNA or the enzymes involved in DNA replication
Either:
Physically block the replication process
Or, cause non-viable mutations to occur during DNA replication
Bacteria die without replicating
Drug class: fluoroquinolones

Question 10

Bacteriostatic drugs

Answer 10

Slows replication rate of the bacteria at proper dose
Allows the immune system to clear the bacteria more effectively
Must have a functioning immune system

Question 11

Bacteriocidal drugs

Answer 11

Kill bacteria

Question 12

MIC

Answer 12

Minimum inhibitory concentration
Lowest concentration of an antibiotic that will completely inhibit growth of specific bacteria in vitro

Question 13

MBC

Answer 13

Minimum bacteriocidal concentration
Lowest concentration of an antibiotic that will kill specific bacteria

Question 14

Dosing on antibiotics depends on and what happens if you don’t get it right

Answer 14

MIC or MBC must be reached at the site of infection for the drug to be effective
Depends on
Dose in mg/kg
Route of drug administration
Frequency of dosing
Failure to achieve at least the MIC will result in:
Failure to treat infection
Increased risk of drug resistance

Question 15

Narrow spectrum antibiotics

Answer 15

only work on either Gram positive OR Gram negative bacteria
Considered more specific

Question 16

Broad spectrum antibiotics

Answer 16

work on both Gram positive and Gram negatives (but not necessarily all)
Considered less specific

Question 17

1st line antibiotics

Answer 17

“First choice” antibiotics in ANY situation
Main criteria:
Bacteriocidal
Better chance of treating infection
Narrow spectrum
Least side effects to the patient

Question 18

How antibiotics are used

Answer 18

Used to control bacteria in or on the body
Four reasons for using antibiotics in veterinary medicine:
Therapeutic Use
Prophylaxis
Metaphylaxis
Growth Promoter

Question 19

Therapeutic use of antibiotics

Answer 19

Using antibiotics to treat the bacterial cause of an infection that is occurring now
Gold standard requires identifying a bacterial agent of disease and selecting the right drug
Culture and other identification tests to determine genus at minimum
Antimicrobial testing for best drug
Limitation: Time (and $) for culture and sensitivity testing
Least likely to cause drug resistance

Question 20

Kirby bauer test is and tests for

Answer 20

Standard test for antibiotic sensitivity and resistance
Bacteria is cultured on the surface of a solid media
Discs containing different antibiotics are placed on the media
Drugs that are effective stop bacteria growth
Reporting:
Sensitive (S) – Inhibits growth at therapeutic dose - recommended
Intermediate (I) – Inhibits growth if dose is higher than recommended
Resistant (R) – Dose to inhibit bacteria cannot be achieved

Question 21

Prophylaxis use of antibiotics

Answer 21

Using antibiotics to prevent an infection that might occur
AKA preventative treatment
Can be very effective
Eg. Giving an antibiotic before an intestinal surgery to prevent the development of infection
Note: Surgical prophylaxis should NEVER BE a substitute for good aseptic technique and surgical skill

Question 22

Metaphylaxis use of antibiotics

Answer 22

The timely mass medication of a group of animals to eliminate or minimize an expected outbreak of infectious disease
Used at therapeutic dose
“Group prophylaxis”
Most common in cattle, swine, poultry

Question 23

Growth promoter use of antibiotics

Answer 23

Addition of antibiotics to feed or water to mass medicate a group of animals in order to increase feed efficiency
Often used in low (sub-therapeutic) concentrations
Most commonly used in poultry, also swine and beef
Example:
Low levels of tetracycline in water enhance growth rates in chicks
Controversial

Question 24

Antimicrobial resistance is

Answer 24

AMR
Acquired ability to survive despite presence of a therapeutic concentration of a chemical that is normally lethal
“Resistance” can apply to bacteria, viruses, fungi, parasites and insects
The “chemical” may refer to antimicrobials, antiparasitics, disinfectants

Question 25

3 major mechanisms of AMR

Answer 25

Spontaneous mutation of target proteins so drug can’t bind
Acquiring plasmids that contain resistance genes
Cross-resistance due to acquiring the drug efflux pump

Question 26

Spontaneous mutation of AMR

Answer 26

Bacteria have fast generation times so change due to spontaneous mutation can occur rapidly
Most common change is to the target protein so drug can no longer bind

Question 27

Plasmid-based resistance of AMR

Answer 27

Plasmid genes can contain:
An altered enzyme that drug cannot bind to
Enzyme that breaks down drug
Transporters that prevents drug entry or that removes drug
Once bacteria have a plasmid, it is passed to all progeny cells AND can be passed to adjacent bacteria → can rapidly spread AMR
Example: beta-lactamase gene is a form of plasmid-based resistance

Question 28

Drug efflux pump of AMR

Answer 28

Bacteria acquire a new transporter gene that pumps drugs out of the bacteria cell
Pump found on bacterial cell membrane
When drugs enter the cell, the pump removes immediately
Is able to pump out many different classes of drugs
This resistance is developed to one drug but then provides resistance to other drugs
Called cross-resistance

Question 29

Fluoroquinolone Antibiotics and Cross-Resistance

Answer 29

Fluoroquinolones are a class of antibiotic that blocks replication of bacterial DNA
One of newest classes, introduced in 1980’s
Bacteriocidal, relatively safe, broad spectrum
Bacteria that are exposed to, but not killed by this class of antibiotic have a high risk of developing mutations that create the efflux pump method of cross- resistance
Category 1 - Very High Importance Antibiotic according to WHO, Health Canada
Intended for use in-hospital under strict supervision for the treatment of multi-resistant strains of bacteria
When there is no alternate option
Due to increased risk of creating cross-resistance

Question 30

Super bugs

Answer 30

Bacteria that are resistant to multiple classes of antibiotics
Limited treatment options
Problem concerns both human and vet medicine as these bacteria will cross species

Question 31

Concerns with antibiotic resistance

Answer 31

Costs associated with treating
More hospital stays, longer hospital stays
$$$$ drugs
Costs in human health
Many of our important veterinary pathogens are zoonotic
Resistant strains of E. coli , Staphylococcus, Streptococcus, Mycobacterium Tb….
Prolonged illness/hospitalization/work loss/can’t treat
Will we run out of antibiotics to use?
Human medicine reserves certain antibiotics for treating resistant bacteria
Drug development is very expensive
If new antibiotics come to market, they likely will NOT be available for vet use

Question 32

Risk factors for AMR

Answer 32

Bacteria exposed to sub-therapeutic levels of drug (i.e., less than MIC)
Selecting bacteriostatic drugs
Selecting broad spectrum drugs where target population has a lower MIC or MBC
Incomplete treatment; not all target bacteria are removed
Inappropriate fluoroquinolone use
If bacteria comes from a hospital setting
Increased exposure to different antibiotics
As long as drug is present, there is selective pressure for the resistant strain to flourish

Question 33

WHO Identified Causes of Increasing Antimicrobial Resistance

Answer 33

Resistant organisms being transferred from animals to people
Via meat, dairy, manure
Overuse in livestock
Treating without identification of bacteria causing disease
Treating diseases of viral origin with antibiotics
Lack of antibiotic sensitivity testing
Prescribing broad-spectrum drugs (rather than narrow spectrum)
Using drugs in a manner not approved
Not completing full course of medication
Some bacteria remain and can develop resistance
Groundwater contamination from urine and feces from treated livestock
Inappropriate disposal of antibiotics
Overuse of antibacterial cleaning products

Question 34

What types of antibiotics are being used in livestock?

Answer 34

Sulphonamides > tetracyclines >β-lactams > aminoglycosides (66%)
Same classes that are used in human medicine

Question 35

How to Increase Antibiotic Effectiveness and Avoid Resistance?

Answer 35

Identify if bacteria is part of the disease process
Identify which bacteria is involved
Identify which antibiotic(s) the bacteria is susceptible to, and which it is resistant to
Select a susceptible antibiotic, with the narrowest spectrum
Use drug as intended (correct dose for that species, proper indication, frequency, duration)
Treat until infection is resolved

Question 36

Drugs that target cell wall synthesis are effective against which type of bacteria?

Answer 36

Gram +

Question 37

How can antibiotics block protein synthesis?

Answer 37

Binding to the ribosome and blocking its function
Binding to the tRNA so aa cannot be transported to the ribosome

Question 38

If a drug acts only on gram negative bacteria is it narrow or broad in spectrum?

Answer 38

narrow

Question 39

Drugs that act like detergents affect which bacterial cell structure?

Answer 39

Membrane

Question 40

What is the lowest concentration of an antibiotic that will completely inhibit bacterial growth?

Answer 40

MBC