Antibiotics and Resistance Lec 3

What are the 3 antimicrobial agents

Disinfectants

Antiseptics

Antibiotics

How can antibiotics be delivered?

Topically

Internally

What is the most effective therapeutic agent against bacterial infections?

antibiotics

What are the two major problems with antibiotics

1. less interest from pharmaceutical companies to develop new antibiotics

2. Bacterial resistance to antibiotics always happens

What are the 5 misuses of antibiotics that leads to antibiotic resistance

1. Empiric (blinded) use — giving antibiotic before knowing which bacterium is causing the infection.

2. Use of broad-spectrum agents — affects many bacteria that aren't causing the infection, including harmless ones

3. Pediatric use — when children use antibiotics for colds

4. Patients not completing the full antibiotic course

5. Antibiotics in animal feeds

What is the MIC? What are two ways it can be measured?

Minimum inhibitory concentration.

• The lowest concentration of antibiotic that inhibits growth.

• Measured w/ tubes of culture varying in conc. (low MIC is good)

• Measured with antibiotics strips (quick)

What are the five structures that antibiotics target?

Cell wall synthesis

Protein synthesis

DNA/RNA synthesis

Folate Synthesis

Cell membrane alteration

What is are 2 examples of a β lactam antibiotic?

Penicillin

Methicillin

Penicillin: What structure do β lactam antibiotics contain?

A "β lactam ring."

Explain what the B lactam ring does.

• what does it inhibit (and how does it inhibit)

• stops peptide cross linkage which inhibits cell wall synthesis

• stops it by binding to the penicillin binding proteins “PBPs” which makes the cell wall

Penicillin: What does bacteria do to prevent it b lactam from working?

Creates B lactamase

• An enzyme that destroys the β lactam ring and thus the antibiotic.

• this makes the bacteria resistant

what was the solution to prevent bacteria from destroying penicillin?

• modified penicillin into methicillin

• this cannot be cleaved by B lactamases

How can some bacteria still resist methicillin? What is it encoded by?

They produce a different penicillin-binding protein (e.g. PBP2a) which can’t bind to methicilin.

• encoded by mec.

What is vancomycin? What is its purpose?

A glycopeptide antibiotic

• inhibits cell wall synthesis

• used as a last resort drug

How does vancomycin work? How does resistance stop vancomycin from working?

• binds peptide linkages (residues) and inhibits transpeptidation

• changes the residue order so that vancomycin cant bind

Which genes encode vancomycin resistance?

The van genes.

What is the paradoxical concept regarding antibiotic use?

the use of antibiotics actively selects for antibiotic resistant bacteria

this diagram basically shows how using an antibiotic creates more resistance than when not using an antibiotic

What was shown in the harvard video?

 Bacteria that is sensitive to antibiotic can form resistance to extremely high concentrations 

What are the five bacterial strategies for antibiotic resistance

• Stops antibiotic entry

• Modifies antibiotic

• Efflux antibiotic (pumps it out)

• Changes target of antibiotic

• Bypasses antibiotic action

Besides selecting for random mutations, how else can antibiotic resistance arise?

It can be genetically encoded

How high can the level of resistance from antibiotic resistance genes be?

can produce very high levels of antibiotic resistance

Where are resistance genes often encoded? What do they allow for?

On mobile genetic elements (e.g. plasmids).

• Horizontal gene transfer

What can horizontal gene transfer of resistance genes lead to?

"Superbugs."

• bacterium that has become resistant to antibiotics

What is horizontal gene transfer

New genes are acquired from another source, rather than altering gene function through mutations.

Why is horizontal gene transfer important for antibiotic resistance?

It lets bacteria acquire resistance genes from another source instead of waiting for a mutation. This is how resistance can spread between bacteria and lead to "superbugs"

What is K. pneumoniae?

• gram?

• causes what?

• resistant to what?

• gram neg

• cause of n. pneumonia

• B lactamase resistant

What is C. diff?

• gram?

• key feature

• where is it found

• causes what condition?

• gram pos

• ENDOSPORE former

• found in nursing homes and hospitals

• causes pseudomembranous colitis

Why is C. difficile hard to eradicate from the environment?

Its endospores can be very difficult to eradicate

What is the mode of transmission of C. difficile?

Through the spore, by the fecal-oral route.

What disease does C. difficile cause? What causes it?

Pseudomembranous colitis

• aka Antibiotic-associated diarrhea

• An inflammatory condition of the large intestine.

Caused by taking antibiotics which kill the good bacteria

What are symptoms of Pseudomembranous colitis?

diarrhea, abdominal pain

What two things combine to set up C. difficile overgrowth?

• Suppression of the normal microbiota

• persistence of C. difficile endospores.

What happens to the spores after the antibiotic is stopped?

They germinate, and C. difficile overgrows and produces toxins.

What causes the damage in pseudomembranous colitis?

The exotoxins, which damage and inflame the lining of the large intestine.

What kind of toxins does C. difficile produce?

produces A-B toxins

• called the large clostridial cytotoxins

What does the A domain do?

What does the B domain do?

A: Active portion of the toxin that carries the enzymatic activity.

B: It is responsible for binding and uptake by the host cell.

What should be done about the antibiotic that triggered c.diff?

Discontinue the inciting antibiotic if it is still being used.

What supportive treatment is used for c.diff?

Fluids

What should be avoided in c.diff treatment?

Antidiarrheal agents

• would cause decreased toxin clearance

What is fecal microbiota transplantation?

Putting a filtered donor fecal sample into a patient to restore a stable, healthy gut microbiota.

How does Fecal microbiota transplantation help treat recurrent C. difficile infection?

• Antibiotics kill C. difficile but leave spores and a damaged microbiota

• causes infection to return

• FMT restores a stable, healthy gut microbiota, which leads to resolution of symptoms.

What was the fecal microbiota transplantation study about?

It compared FMT with standard vancomycin treatment in patients with recurrent C. difficile infection, to see which was better at curing them without relapse.

What were the results of FMT study?

FMT worked much better

About 94% of the FMT group were cured, compared to roughly 23-31% in the vancomycin groups.