02 Study guide: cell wall & membrane

Question 1

What are the 4 major classes of beta lactam antibiotics, and how can one recognize names of drugs in each class?

Answer 1

Penicillins: (-cillin)
Cephalosporins: (-cef-)
Carbapenems: (-penem)
Monobactams (aztreonam)

Question 2

What are the 4 major classes of penicillins?

Answer 2

• Natural Penicillins:
  
  • Penicillin G
  • Penicillin V
• Anti-staphylococcal:
  
  • Nafcillin and Oxacillin
  • Dicloxacillin
• Amino/ Broad spectrum:
  
  • Ampicillin
  • Amoxicillin
• Extended Spectrum:
  
  • Piperacillin + tazobactam

Question 3

Name 4 examples of beta lactamase inhibitor drugs.

Answer 3

• Clavulinic Acid
• Sulbactam
• Tazobactam
• Avibactam

Question 4

What feature is shared in the names of all glycopeptide antibiotics?

Answer 4

-van-

Question 5

Name the classes (and the 2 additional “other” drugs) that target bacterial cell membranes.

Answer 5

• Other cell wall antibiotics: fosfomycin, bacitracin
• Lipopeptides: dapotomycin
• Polymyxins (-myxin)

Question 6

Name 2 drugs that primarily target bacterial cell membranes.

Answer 6

Daptomycin: disrupts cytoplasmic membrane

Polymyxins: disrupt the outer membrane + cytoplasmic membrane

Question 7

What are the two major components of peptidoglycan?

Answer 7

Polysaccharides: 2 alternating sugars - N-acetylglucosamine (G) and N-acetylmuramic acid (M)

Peptides: five amino acid chain, linked N-acetylmuramic acid sugar

Question 8

What are the 3 major steps in PG synthesis – what happens in each step?

Answer 8

Monomer synthesis & transport: in cytoplasm, building blocks are made from amino acids & sugar by enzyme (Mur enzyme), then transported to the cell surface by lipid carriers.

Glycan polymerization: at cell surface, N and M sugars are connected into strands via transglycosylation by penicillin binding proteins (PBPs)

Polymer cross-linking: strands are linked by transpeptidation, when penicillin binding proteins (PBPs) remove the peptide’s terminal D-alanine to cross-link it to another peptide

Question 9

What are the roles of PBP (both roles), Mur enzymes, and flippase II enzymes?

Answer 9

PBP often have both transpeptidase domain and glycosyltransferase domain

Mur A enzyme: building blocks made from amino acids and sugar

_Flippase II enzyme_s: transport building blocks to cell surface

Question 10

Which steps in the PG synthesis pathway are targeted by: β lactams, glycopeptides, fosfomycin and bacitracin - and to what target does each one bind?

Answer 10

Photo attached below

Question 11

What are 2 drugs that target the cell membrane, and how does each work?

Answer 11

Daptomycin: disrupts cytoplasmic membrane

Polymyxins: disrupt the outer membrane + cytoplasmic membrane

Question 12

What are the 4 primary mechanisms by which bacteria become resistant to β lactam drugs?

Answer 12

1. Inactivation of antibiotic by bacterial beta-lactamase: these enzyme catalyzed opening of the antibiotic’s beta-lactam ring
2. Reduced uptake of antibiotic: specific to gram-negative bacteria (impervious outer membrane)
3. Antibiotic efflux: gram negative bacteria may produce drug efflux pumps which toss some beta-lactam antibiotics back out
4. Alteration of the antibiotic’s target: bacteria produce slightly different PBPs that antibiotics can’t bind to: development of a new PBP (PBP2a) by S. aureus is how the “superbug” MRSA arose

Question 13

Which of the 4 mechanisms of how bacterial resistance develops against cell wall / membrane-targeted agents is the most common?

Answer 13

Inactivation of antibiotic by bacterial beta-lactamase

Question 14

What is the function of bacterial beta lactamase enzymes?

Answer 14

they protect beta-lactam antibiotics from ring-destruction (counter-defense)

Question 15

What type of bacteria are more likely to develop antibiotic resistance by altering drug uptake / efflux – gram positive or negative (and why)?

Answer 15

Gram negative. They have an impermeable outer membrane.

Example: development of a new PBP (PBP2a) by S. aureus is how the “superbug” MRSA arose

Question 16

Give 3 examples of how bacteria can develop antibiotic resistance by altering antibiotic binding targets.

Answer 16

1. these enzymes catalyze opening of the antibiotic’s beta-lactam ring
2. most but not all bacteria produce beta-lactamase enzyme to defend themselves from antibiotics
3. bacteria make hundreds of different beta-lactamase enzymes, each degrades a particular range of beta-lactam antibiotics

Question 17

What is the mechanism by which MRSA developed resistance to penicillins?

Answer 17

Alteration of the antibiotic’s target: bacteria produce slightly different PBPs that antibiotics can’t bind to

• all available beta lactam antibiotics (except two new cephalosporins) fail to bind to MRSA’s new PBP (PBP2a)
• MRSA is currently treatable with vancomycin, daptomycin and ceftaroline

Question 18

Which class of beta lactam antibiotics has the broadest spectrum of activity?

Answer 18

Carbapenems (-penem): Imipenem, Meropenem

Question 19

Which 1 class of beta lactams antibiotics has activity against gram negative bacteria only?

Answer 19

Monobactams: Aztreonam (gram negative only)

Question 20

Among the 4 categories of penicillins, which 2 have a narrow spectrum of activity, and which 1 has the broadest spectrum of activity?

Answer 20

1. Narrow spectrum:
   
   1. Natural Penicillins: Penicillin G (IV), Penicillin V (PO)
   2. Anti-Staphylococcal: Naficillin and Oxacillin (IV), Dicloxcillin (PO)
2. Broadest spectrum:
   
   1. Extended Spectrum: Piperacillin + tazobactam (IV/IM)

Question 21

All penicillins have activity against which type of bacteria – gram positive or gram negative?

Answer 21

Gram Positive!

Question 22

Name 6 antibiotic classes / subclasses / drugs that can be used to treat MDR strains of bacteria

Answer 22

1. Cephalosporins (5th generation, IV): Ceftaroline, ceftolozane + tazobactam
2. Carbapenems: Imipenem (combine with beta-lactam inhibitor to provide activity against MDR bacteria)
3. Glycopeptide: Vancomycin (more use recently due to rise in MDR bacteria)
4. Other cell wall agents: Fosfomycin
5. Cell membrane agents: Polymyxins
6. Daptomycin (Lipopeptide - cell membrane agent)

Callie’s Car Glide Other Cell Damn

Question 23

Which of the β lactams is least likely to have cross-reactivity in patients with penicillin allergy?

Answer 23

Monobactams: Aztreonam (NO CROSS REACTIVITY)

Question 24

Which β lactam drug class is associated with the highest risk of C difficile colitis?

Answer 24

Cephalosporins (3rd generation): cefituten (PO), cefotaxime, ceftriaxone (-one, -ten, -ime)

Question 25

Which antibiotic drug produces a classic constellation of side effects including histamine-mediated flushing, ototoxicity and nephrotoxicity?

Answer 25

_Glycopeptides:_ Vancomycin

Question 26

Which β lactam subclass can cause alcohol intolerance, hemolysis, impaired coagulation and *C diff.* colonic overgrowth?

Answer 26

Cephalosporins (3rd generation): cefitu**ten** (PO), cefotax**ime**, ceftriax**one** (-one, -ten, -ime)

Question 27

Which β lactam drug is mainly cleared by renal metabolism?

Answer 27

_Carbapenems (-penem)_: **Imipenem**, Merapenem, Doripenem, Ertapenem

Question 28

Which one of the 4 classes of beta lactam antibiotics is only available IV (and why)?

Answer 28

_Carbapenems (-penem)_: **Imipenem**, Merapenem, Doripenem, Ertapenem Because they have very short half lives

Question 29

Give examples of 2 antibiotics that are more likely to cause concentration-dependent risk of seizures?

Answer 29

1. Natural Penicillins: Penicillin G (IV or IM) 2. Carbapenems (-penem): concentration-dependent seizure risk (**Imipenem**, Merapenem, Doripenem, Ertapenem) [Imipenem highest risk]

Question 30

How can one recognize the names of beta lactamase inhibitor drugs, and what is the one exception to this rule?

Answer 30

1. Beta Lactamase inhibitor (usually-bactam): 1. Sulbactam, Tazobactam, Avibactam **Exception**: Clavulanic Acid

Question 31

What is the purpose of beta lactamase inhibitor drugs?

Answer 31

Combined with beta lactam antibiotics to overcome bacterial drug resistance

Question 32

Are beta lactamase inhibitors generally administered with non-beta lactam antibiotics?

Answer 32

No, it is usually administered with beta lactam antibiotics

Question 33

Which antibiotic must be administered in combination with cilastatin, and what is the purpose of cilastatin in this combination?

Answer 33

Carbapenems: Imipenem (must combine with cilastatin (DHP-1 inhibitor) to achieve therapeutic concentration because DHP-1 metabolizes carbezenems