Lecture 2 Mechanism of Penicillin / Endocartitis

Question 1

How does penicillin work?

Answer 1

Penicillin works on the cells wall of the bacteria. it degrades the cell wall.

Question 2

what is the main component of the bacterial wall?

Answer 2

Peptiglycan. Peptigylcan is repeated sugars: Nam and Nag

Question 3

what maintains the 3D structure of the bacterial cell wall?

Answer 3

The 3D structure is maintained by cross-link that give structural integerity to the cell wall.

Question 4

how are these cross-linking preformed?

Answer 4

Peptides hanging off the NAMS because the 5th peptide is cleaved when a transpeptidase enzyme forms a link between the peptide chains hanging off the NAMS.

Question 5

How does the penicillin work on the cell wall of the bacteria?

Answer 5

Penicillin binds to transpeptidase and prevents peptides cross-linking. Hence, it breaks down the bacterial cell wall by inhibiting the 3D structural integrity and everytime the cell wall breaks down, it cannot not use transpeptidase to repair → bacteria dies

Question 6

what is the Hypothesis of Autolysin?

Answer 6

The bacteria uses it’s last attempt to repair cell wall when it is badly damaged.

Question 7

what are Beta-Lactams?

Answer 7

B-lactams refers to any antibiotics that has the garage ring structure to inhibit transpeptidase to kill bacteria.

Question 8

what is the percentage of S.aureus that are not sensitive to penicillin?

Answer 8

10%

Question 9

What are the derivative of Beta-lactam?

Answer 9

B-Lactam antibiotics include all penicillin derivatives, cephalosporins, carbapenems, and monobactam but comes from different organism.

Question 10

Which penicillin is more resistance of stomach acid? and why ?

Answer 10

Penicillin V — with added Oxide group makes the penicillin more resistant to stomach acid.

Question 11

What penicillin is not resistant to stomach acid? and how is it given?

Answer 11

Penicillin G is a form of penicillin we give intraveously because it can be degraded by the stomach acid if given orally.

Question 12

Why is only 10% of s. aureus resistant to penicillin?

Answer 12

• S. aureus has an enzyme that that breaks down and hydrolysis the b-lactam ring.
• Enzyme is called penicillinase, this enzyme functions to digest penicillin.

Question 13

Why is Flucoxacillin used as an antibiotics for S. Pyogenes and S. aureus instead?

Answer 13

• Flucoxacillin also have the same structure as beta-lactum, but it has a different side change that makes it more complicated. The side actually swings around and make an interaction with the beta-lactum ring. It prevents S.aureus beta-lactumase/penicillinase getting access to the beta-lactum ring and hydrolyse it.
• So Flucoxacillin is a Anti Staphylococcal / penicillin antibiotics, also known as beta-lactumase stable antibiotic.
• MRSA could be thought as FRSA (Flucoxacillin Resistence Staph.Aureus) FRSA have changed the transpepdiase enzyme such as the penicillin or any drug will not bind at all. Causing NO Beta-lactum drug to bind.

Question 14

what is endocarditis?

Answer 14

Inflammation on heart valves or other cardiac structures for example ventricular septal defects) almost always caused by bacterial infection.

Question 15

what organism cause endocarditis?

Answer 15

Common caused by S.Aureus and Commonly caused by Strephycoccus germs like S.pyogenes.

Question 16

what stain of S.pyogenes is more likely to cause endocarditis?

Answer 16

Streptococcus salivarius is a bacteria that lives in our mouths, it’s implicated in causing plaque and dental caries.

Question 17

Compare and contrast Rheumatic fever and endocarditis.

Answer 17

(RH) The heart valves has been damaged, they are inflammed and damaged by the immune system and they haven’t been damaged by bacteria.

• Immune driven
• No Bacteria is found on someones heart who has Rhuematic fever.

(EC) The heart contain puss and vegitations on them

• Clumps of bacteria living and growing on the heart valves
• Batcerial heart valve infection

Question 18

what is the function of cusp found in the heart?

Answer 18

As the ventricles relaxes, the 3 cusp of the aortic valves snaps closed to prevent the blodd reflowing back into the heart.

Question 19

what is the main function of the heart?

Answer 19

Heart beats → pumps → squeezes → let oxygenated blood fire up into the aorta → circulate around the body.

Question 20

How does Rheumatic fever occur?

Answer 20

where the heart valves may leak.

Question 21

Define regurtation.

Answer 21

regutation is when the blood flows backwards. This is also called turbulent blood flow.

Question 22

what is turbulent flow?

Answer 22

• Turbulent blood flow is very dangerous because it causes pressure damage.
• The pressure of the blood can damage the cells lining the heart valves or the related structures.
• This damage can expose the connective tissues under those cells

Question 23

what happened when the tissue is damage causing the connective tissue to be exposed?

Answer 23

• When the connective tissue is exposed it will be come very sticky and the anything can stick on it like like BACTERIA.
• Once the germs and bacteria are stuck on the heart, they will initiate the immune response.

Question 24

What is the immune response after the damage?

Answer 24

The immune response is in the blood stream rather than the endothelial cells.

The way the immune system anchor the response is by clotting the bacteria and allowing the immune cells to come and fight the bacteria.

Question 25

What is the end result from the damaged cells and exposed connective tissues of the heart?

Answer 25

hey end up forming a mass and that mass is called vegitations. Results in a mass of bacterial infection that our body cannot clean or get rid of on our own.

Question 26

what does the vegitation contain ?

Answer 26

bacteria, clots, clotting proteins, clotting cells, platelets, and immune white blood cells.

Question 27

where does Endocarditis can occur ?

Answer 27

Endocarditis can occur on any heart valves, septal defects, pacemakers wire...

Question 28

What are some common risk factors for endocarditis?

Answer 28

1. Valve damage - rhematic heart disease - mitral valve prolapse - bicuspid aortic valve - congenital heart disease 2. old age 3. prothetics valves 4. other cardiac device 5. intravenous drug use 6. recent cardiac surgery 7. central venous catheters

Question 29

what are the system clinical feature of endocarditis?

Answer 29

``` Fever (80%) Chills (60%) Aches / pain (20%) Weight loss Sweating Lethargy ```

Question 30

what are the valves clinical features of endocarditis?

Answer 30

Leaking Cardiac abscess Need surgery (30%)

Question 31

what are the diagnosis of endocarditis?

Answer 31

1. Persistent bacteraemia with an usual organism 2. ultrasound of heart valves to visualise vegetations (clumps of bacteria and immune cells) 3. presence of other phenomena

Question 32

what are the treatment of Endocarditis ?

Answer 32

1. Sterilise the valves with surgery and antibiotics 2. Unusal treatment is for 4 weeks with bacteriacidal antibiotics → Treatment success correlateds with keeping antibiotics concentration high for most of the dosing intervals → In this case Penicillin will be an effecient bactericidial antibiotic because Bacterial Streptococcus salivarius is sensitive to it according to the MIC. 3. 10-30% mortality