Inhibitors of Cell Wall Synthesis

Question 1

Antibiotics that inhibit cell wall synthesis require what?

Answer 1

Require a cell that is actively dividing. Little to no effect if not growing.

Question 2

Which antibiotics are cell wall inhibitors by peptidoglycan?

Answer 2

Bacitracin and vancomycin

Question 3

What antibiotics are cell wall inhibitors by transpeptidase

Answer 3

Pencillins

Cephalosporins

Question 4

Penicillins. Differences in drugs are due to

Answer 4

Structure. Side chain affects antimicrobial spectrum, stability to stomach acid, cross hypersensitivity and susceptibility to degradative enzymes.

Question 5

What do all penicillins have in common?

Answer 5

All have the B-lactam ring.

Question 6

MOA by penicillins

Answer 6

B lactam antibiotics form a covalent bond with the bacterial enzyme transpeptidase. This inhibits the catalytic activity of the enzymes.

• Prevents elongation or cross linking of peptidoglycan.
• Leads to autolysis

Question 7

Transpeptidase enzymes

Answer 7

Group of bacterial enzymes that are anchored in the cytoplasmic membrane and extend into the periplasmic space.

responsible for the assembly, maintenance, and regulation of the peptidoglycan portion of the bacterial cell wall.

Question 8

“easy to kill gram negative” and “hard to kill gram negative”

Answer 8

Gram negative are surrounded by outer envelope that acts as a barrier.
Easy to kill have channels that allow entry.
hard to kill have restrictive porins and are resistant to many antibiotics (pseudomonas)

Question 9

Example of a hard to kill gram negative bacteria

Answer 9

pseudomonas

Question 10

Natural penicillins are obtained from

Answer 10

mold fermentation. Susceptive to inactivation by enzymes that bacteria produce, called Beta lactamases. Beta lactamases can destroy penicillin molecule.

Question 11

beta lactamase

Answer 11

Enzymes that bacteria produce to destroy penicillin molecule.
Same as penicillinase.

Question 12

penicillinase.

Answer 12

Enzymes that bacteria produce to destroy penicillin molecule.
Same as beta lactamase.

Question 13

When are penicillinase-resistant penicillins used?

Answer 13

For the treatment of penicillinase producing staph. Avoid over use to prevent resistance.

Question 14

examples of penicillinase-resistant penicillin

Answer 14

Nafcillin

Oxacillin

Question 15

Methicillin. When should it be used?

Answer 15

High toxicity. causes interstitial nephritis.

Used only to identify resistant strains of S. Aureus (MRSA.) MRSA is resistant to all available B-lactam antibiotics.

Question 16

MRSA is susceptible to

Answer 16

Vancomycin.

Question 17

Extended spectrum penicillins

Answer 17

designed to maintain Gram + and easy gram negatives

Resistance is a major problem. Often combined with a penicillinase inhibitor.

Question 18

natural resistance vs acquired resistance

Answer 18

Natural: organisms that lack a cell wall or have a cell wall that is impermeable to the drug.

Acquired: occurs via plasmid transfer. Can encode for resistance to multiple agents.

Question 19

Beta lactamase activity

Answer 19

Enzyme hydrolyzes the beta lactam ring in the antibiotic. Results in loss of the bactericidal activity.

Question 20

3 methods of acquired resistance

Answer 20

Beta lactamase activity
Decreased permeability (efflux pump)
Altered penicillin binding proteins- newer acquired resistance. Cause of MRSA resistance. Lower affinity to antibiotics. Would need to increase conc to an impossible amount.

Question 21

How are antibiotics absorbed

Answer 21

Most are INcompletely absorbed after oral administration. Reach intestine in sufficient amounts to affect intestinal flora (GI issues).

Amoxicillin is almost completely absorbed in stomach- not as much GI issues.

Question 22

Absorption of penicillinase-resistant penicillins.

Answer 22

Destroyed in acidic environments. Must be taken 30-60 minutes before food or 2-3 hours after. Need to decrease acidic environment of food.

Question 23

Distribution of antibiotics

Answer 23

All cross the placenta, but are not teratogenic.
Cannot penetrate bone or CNS unless inflammation.
Cannot reach prostate

Question 24

Hypersensitivities with antibiotics

Answer 24

5-10% of patients have reactions.

• Rash
• Angioedema
• Anaphylaxix

Question 25

Adverse reactions to antibiotics

Answer 25

Diarrhea due to disruption of flora Nephritis (inflamed kidney) especially with methicillin. Neurotoxicity Hematologic toxicities causes decreased coagulation in blood. Be aware if they are on blood thinner!! Cation toxicity

Question 26

Why you should be aware if your patient is on blood thinners and you want to rx an antibiotic

Answer 26

Antibiotics adverse effects include hematologic toxicities- causes decreased coagulation in blood. Will thin blood even more.

Question 27

Why can cephalosporins be given by itself more often?

Answer 27

Because they tend to be more resistant to certain beta lactamases.

Question 28

Spectrum of cephalosporins

Answer 28

First generation: Gram positive coverage. Little gram negative. Second: Extended coverage. Same gram positive and improved gram negative with anaerobic coverage. Third: Less gram positive. Gram negative. 4th: Borad spec. Gram positive like first gen and gram negative like 3rd gen with pull coverage against cefepime. No anaerobic coverage. 5th. Similar to 3rd. Also against MRSA and pneumonia. And against anaerobic. Advanced. Injection only.

Question 29

Which gen to use of cephalosporins. 1. Skin infections 2. Intra-abdominal infections 3. Pneumonia 4. Serious infections for immunocompromised patients

Answer 29

1. 1st 2. 2nd 3. 3rd 4. 4th

Question 30

What cephalosporin to treat MRSA

Answer 30

Ceftaroline

Question 31

Which cephalosporin to treat pseudomonas

Answer 31

Ceftazidime Cefepime Ceftolozane

Question 32

Are cephalosporins susceptible to staph penicillinase?

Answer 32

NO.

Question 33

If patients are allergic to penicillin, what generation of cephalosporins should be used

Answer 33

3rd gen.

Question 34

If patients are allergic to penicillin, which gen of cephalosporins should you avoid

Answer 34

1st gen

Question 35

Beta lactamase inhibitors

Answer 35

Do not have significant antibacterial activity by themselves. They bind to penicillinases and inactivate. This protects the antibiotic from resistance mechanisms.

Question 36

Examples of Beta lactamase inhibitors

Answer 36

Clavulanic Acid

Question 37

Sulbactam

Answer 37

Tazobactam

Question 38

Bacitracin is only available

Answer 38

Topically. When given systemically, will cause nephrotoxicity.

Question 39

Mechanism of action of Vancomycin

Answer 39

Inhibits cell wall synthesis. Binds to alternative proteins in the cells all- weakens peptidoglycan polymerization and damages underlying cell membrane. Not effective against gram negative cell wall synthesis. Very effective against gram positive. Restrict use to treatment with serious infections. Don't want to develop resistance.

Question 40

Administration of Vancomycin

Answer 40

Slow IV fusion Oral absorption poor Orally? Minimal metabolism and eliminated via kidneys.

Question 41

Adverse effects of Vancomycin

Answer 41

Fever Chills Phlebitis at injection site (inflammation at vein) Flushing or shock if rapid infusion.

Question 42

Telavancin

Answer 42

Synthetic derivative of vancomycin. No evidence that it is more effective than vancomycin. Basically same thing. Inhibits cell wall synthesis.

Question 43

Telavancin adverse effects

Answer 43

``` Taste disturbances Nausea Vomitting Insomnia Foamy urine Not be used during pregnancy Caution in cardiac conditions ```

Question 44

Bacitracin MOA

Answer 44

``` Interferes with peptidoglycan synthesis great gram positive coverage Rare toxicity and allergic reactions Safe on pregnancy Only available topically. Very nephrotoxic when given systematically. ```

Question 45

What infections do you use bacitracin on

Answer 45

Infectious blepharitis and overnight coverage in treatment of bacterial corneal ulcers.

Question 46

Daptomycin MOA

Answer 46

Induces rapid depolarization of the cell membrane. Not a true cell wall antibiotic.

Question 47

Daptomycin spectrum

Answer 47

Limited to gram positive. Used for skin infections. Inactivated by pulmonary surfactants- never use for pulmonary infection.

Question 48

Daptomycin pharmacokinetics

Answer 48

90% bound to protein | No hepatic metabolism

Question 49

Adverse effects of daptomycin

Answer 49

``` Constipation Nausea headache Myalgias - muscle aches Insomnia ```

Question 50

Most commonly prescribed cell wall antibiotics

Answer 50

Augmentin (500mg bid for 5-7 days) Reflex (500 mg bid for 5-7 days) ^good for eyelid infections. Bacitracin ophthalmic ointment for overnight coverage.