Lecture 5 - Antimicrobial Drugs and Drug Resistance

What does an antimicrobial do?

Kills or stops the growth of microorganisms

True or False: Antimicrobials are chemical and/or natural compounds.

True

What do antibiotics do?

Specifically target bacteria

True or False: Antibiotics are produced naturally from molds or bacteria.

True

Antibiotics are used in therapy to treat what?

Infections

Antibiotics such as prophylaxis is used to do what?

Prevent disease

Antibiotics such as metaphylaxis is used for what?

In advance of an expected outbreak

Antibiotics can be used as a growth promotion to increase what?

Feed efficiency

What is selective toxicity?

More harm to the pathogen than to the host

What is the spectrum of activity?

Range of microorganisms

What is antimicrobial action?

Killing versus inhibiting growth of microorganisms

What is the mechanism of action?

How it kills the microorganism

True or False: The larger the therapeutic index, the safer the drug.

True

What is a therapeutic index?

A ratio that compares the blood concentration at which a drug becomes toxic and the concentration at which the drug is effective

True or False: The smaller the therapeutic index, the smaller the dose of the drug used and the more carefully the patient needs to be monitored for signs of drug toxicity.

True

What is a broad spectrum antibiotic?

An antibiotic that can target many types of bacteria

What are broad spectrum antibiotics useful for?

Useful for when you have no time to identify the bacteria

What can using broad spectrum antibiotics when they’re not needed create?

Can create antibiotic resistant bacteria that are hard to treat

What is a narrow spectrum antibiotic?

An antibiotic that targets only a few types of bacteria

True or False: Using narrow spectrum antibiotics usually requires bacterial identification, and it is less disruptive to normal flora.

True

What do bacteriostatic antibiotics do? What does “-static” mean?

Prevent bacteria from multiplying, “-static” means staying stable

What do bactericidal antibiotics do? What does “-cidal” mean?

Kills the bacteria, “-cidal” means kill

Can you prescribe bacteriostatic and bactericidal drugs together?

No

True or False: Some antibiotics can be both bacteriostatic and bactericidal, depending on the dose, duration of exposure, and the state of the invading bacteria.

True

What are the 5 mechanisms of action?

1. Inhibition of cell wall synthesis
2. Distribution of cell membrane (plasma membrane)
3. Inhibition of protein synthesis
4. Inhibition of nucleic acid synthesis
5. Inhibition of metabolic pathways

Antibiotics disrupt essential processes or structures in the bacterial cell. This does what?

Either kills the bacterium or slows down bacterial growth

How do antibiotics inhibit the synthesis of cells walls?

By inhibiting peptidoglycan synthesis

What do antibiotics that inhibit cell wall synthesis require to be maximally effective?

Actively growing cells

Are antibiotics that inhibit cel wall synthesis bacteriostatic or bactericidal?

Bactericidal

How do antibiotics disrupt the cell wall membrane (plasma membrane)?

By binding to the phospholipids of the membrane and losing the cytoplasm and cell contents

Are antibiotics that disrupt the cell membrane (plasma membrane) bacteriostatic or bactericidal?

Bactericidal

True or False: Protein synthesis is a multistep process where DNA is first transcribed into a molecule of single-stranded messenger RNA (mRNA), Then, ribosomes translate it with the help of transfer RNA (tRNA) into long strings of amino acids, which become proteins.

True

How do antibiotics inhibit protein syntehsis?

They inhibit either the translation or transcription of protein, so they impair bacteria growth by preventing them from making proteins

Are antibiotics that inhibit protein synthesis bacteriostatic or bactericidal?

Bacteriostatic

Antibiotics that inhibit nucleic acid synthesis interfere with what?

Either DNA replication or RNA transcription

Are antibiotics that inhibit nucleic acid synthesis bacteriostatic or bactericidal?

Bactericidal

Antibiotics that inhibit metabolic pathways do what?

Inhibit the folic acid synthesis pathway (all bacterial cells require folic acid to grow)

True or False: The two antibiotics that inhibit the metabolic pathways are sulfamethoxazole and trimethoprim.

True

Are the antibiotics that inhibit metabolic pathways (sulfamethoxazole and trimethoprim) bacteriostatic or bactericidal when used individually? Are they bacteriostatic or bactericidal when used in combination?

Individual: bacteriostatic, Combination: bactericidal

What is synergism?

When 2 antibiotics are administered simultaneously so they can exert an additive effect (the effect is more potent than if each antibiotic were used individually)

What is antagonism?

When drugs are less effective when used in combination than when used individually

Antimicrobial resistance is accelerated how?

When the presence of antibiotics pressures the bacteria to adapt

True or False: Antibiotics kill some bacteria that cause infections, but they also kill helpful bacteria that protect our body from infection.

True

True or False: Drug resistance is spread by being prescribed with antibiotics, developing resistant bacteria in the gut, and then spreading it through contaminating objects (human), contaminating feed with water that was contaminated with feces (animals).

True

What are the two types of bacterial resistance?

Intrinsic resistance and acquired resistance

What is intrinsic resistance?

When a bacterial species is naturally resistant to a certain antibiotic or family of antibiotics, without the need for mutation or gain of further genes.

What is acquired resistance?

When a type of bacteria changes in a way that protects it from the antibiotic

In what two ways can bacteria acquire resistance?

Mutation and gene transfer

What is acquiring resistance through mutation?

A genetic change that helps the bacteria survive

What is requiring resistance through gene transfer?

Getting DNA from bacterium that is already present

When a bacteria is exposed to antibiotics there are three possible outcomes - they will die, they will stagnate (not multiply), or they will multiply. What are the three main factors that will predict which is more likely to happen?

Antibiotic concentration, bacterial mutation, and bacterial exchange

What are the 4 mechanisms of resistance?

1. Altered target
2. Enzyme degradation
3. Efflux pump
4. DNA mutation and gene transfer

Which mechanism of resistance is common?

Altered target

What is the altered target mechanism of resistance?

When a mutation on the bacteria alters the receptors that transport the drug, so the drug cannot enter the bacterial cell.

What is the enzyme degradation mechanism of resistance?

Destroying ot inactivating the drug before it enters the bacterial cell

What is the efflux pump mechanism of resistance?

These pumps pump antibiotics out of the cell preventing them from reaching lethal concentrations

What is the DNA mutation and gene transfer mechanism of resistance?

DNA mutation: Some bacteria mutates when they multiply and some of those mutations can make the bacteria resistant to drugs
Gene transfer: Bacteria that have drug resistant DNA may transfer a copy of these genes to other bacteria

Gene transfer occurs through what 3 main routes?

Transduction, transformation, and conjugation

What is transduction gene transfer?

Bacteriophages mediate transfer of DNA between bacteria vis transduction

What is transformation gene transfer?

Some bacteria are able to take up free DNA from the environment and incorporate it into their chromosome

What is conjugation gene transfer?

A sex pilus forms between two bacterial cells through which a plasmid is transferred from one to the other

What are 5 ways pets develop antimicrobial resistance?

1.Recieving a low dose of bacterial antibiotics
2. Owners forgetting to give medicine
3. Owners skipping the dose
4. Owners not giving the right dose
5. Owners stopping antibiotics before the prescription is finished

What is antimicrobial stewardship?

The actions veterinarians take individually and as a profession to preserve the effectiveness and availability of antimicrobial drugs through judicious use