Peptide Antimicrobials (MC) - Block 2

Question 1

Describe the characteristics of ABX mixutures of cyclic peptides?

Answer 1

1. Uncommon a
2. Common aa are with D conformation
3. Pendant fatty acid chain
4. Arichitecture protect from rapid metabolism
5. Highly toxic, but reserved for serious situations

Question 3

Because of the peptide stucture, what are strategies used to avoid proteolysis?

Answer 3

1. Cyclization
2. Use of abnormal amino acids (non-human/uncommon and D chemistry)

Question 4

What is the general MOA of cyclopeptides?

Answer 4

Attach themselves to bacterial membrane and interfere with semipermeability

Question 5

Common ADR of cyclopeptide?

Answer 5

1. Nephrotoxicity
2. Auditory nerve damage
3. ANaphylactoid rx
4. Drug rash (red man syndrome) -> slow infusion rate

Question 6

What is the function of the proline?

Answer 6

turns of molecule -> cyclic

Question 7

MOA of vanc?

Answer 7

1. Binds to D-ala D-ala, blocking PBP from bind to PG by 5 H-bonds
2. Indirectly inhibits transglycosylases -> inhibits linking between NAG-NAM
3. Indirectly inhibits transpeptidases -> inhibits peptide cross-linking

Question 8

Resistnce to vanc?

Answer 8

Development of D-ala D-ala lactacte cell wall intermediate coded by van enzymes (A-E):
* Lowers binding affinity
* Loss of H-bonding affinity
* Van-associated enzymes that supply lactate for muation
* Avoparcin is a pesticide similar to vanc structure

Altered target in Enterococci

Question 9

What is VISA contributed to?

Answer 9

Thickened PG layer

Question 10

What are the uses for vanc?

Answer 10

1. C. diff overgrowth
2. MRSA
3. Septicemia
4. Endocarditis

Question 11

What are the types of anaphylactoid rx?

Answer 11

1. Hypotension
2. Wheezing
3. Dyspnea
4. Uticaria
5. Pruritus

Question 12

What is telavancin?

Answer 12

Same MOA as vanc, but also bidns to lipid II in cell membrane through lipophillic side chain (decylaminoethyl) -> depolarization of cells and disruption of barrier function

good for VISA and Sub MIC levels for 10hrs

Question 13

What is lipid II?

Answer 13

Cell wall precursor (immature peptidoglycan) -> binding causes disruption of PG synthesis

Question 14

What type of resistance is more prevailant?

Answer 14

Van A

Question 15

What homolog is a mojority f Dalbavacin in?

Answer 15

B0

Question 16

Describe the structure of Dalbavancin?

Answer 16

1. Lipid tail -> cell membrane and strengthn binding to D-ala D-ala
2. Anudation of carboxyl group increases staphy activity
3. Against Van B

Question 17

How does oritavancin differs from other peptides?

Answer 17

1. Less floppy lipophilic ring: anchors the drug to membrane
2. VanA and Van B activity
3. Inhibtis bacterial RNA synthesis -> rapid bacterial eradication

Question 18

What is this

Answer 18

Cyclinc peptide

Question 19

What is the MOA of daptomycin?

Answer 19

Binds to cell membranes and causes depolization and loss of membran potential:
1. Interupts protein synthesis
2. DNA synthesis
3. RNA synthesis
4. Bactericidal

Question 20

Properties of daptomycin?

Answer 20

1. Lipophilic with high PPB
2. G+ bacteriacidal
3. Targets phospholipid bilayer of membrane disrupting electrical potential
4. C2+ is essential for action
5. VRSA and MRSA
6. Degredation by asp protease at 9-Asp

Question 21

Clincal uses of daptomycin?

Answer 21

Skin/ski structue the infection, bacterial endocarditis

Question 22

What can be a result of daptomycins dcreasing nerve conduction?

Answer 22

1. Parestheisa
2. Bell’s palsy

Question 23

What are the streptogramin?

Answer 23

Quinuprisin/Dalfopristin 30/70 (Synercid)

Question 24

What is the activity of synercid?

Answer 24

1. Resistant G+
2. VRE

Question 25

MOA of streptogramin?

Answer 25

**Dalfopristin (type A):** binds to 50S ribosomal subunit -> conformational change and provides higher bindign affinity for quinupristin **Quiniprisitn (type B):** binds to 50s and inhibits protein synthesis

Question 26

Is there cross resistance with Synercid?

Answer 26

Quiniprist has cross resistance with macrolides and lincosamides, but not dalfopristin

Question 27

DDI of synecid?

Answer 27

Strong CYP3A4 inhibitor

Question 28

MOA of bacitracin?

Answer 28

Bind to phosphate group of the PP (Pyrophosphate)-C55 (Carbon 55) of the M- (NAM) and G- (NAG) subunits of the PG preventing dephosphorylation to the monophosphate (prevents translocation)

Question 29

MOA of polymixin? ADR?

Answer 29

Binds to phosphate group on the cytoplasmic membrane -> break down in membrane integrity ADR: neuro and nephrotox

Question 30

What is polymixin used for?

Answer 30

1. Serious UTI 2. Meningitis 3. Septicemia 4. Bladder irrigation P. aeuriginosa

Question 31

sMOA of colistin

Answer 31

Competitively displaces divalent cations (Ca and Mg) from the phosphate groups of membrane lipids -> disruption of outer cell membrane -> leakage of intracellular contents and bacterial death

Question 32

What is the structure that causes disrupion of phospholipid membrane -> lethal bacterial death?

Answer 32

DAB