Cell Wall Synthesis Flashcards

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1
Q

Penicillin G, V

A

Prototype β-lactam antibiotics (penicillinase-sensitive)

  • Penicilling G → IV and IM form
  • Penicillin V → oral
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2
Q

Penicillin G, V mechanism

A
  1. Bind penicillin-binding proteins (transpeptidases).
  2. Block transpeptidase cross-linking of peptidoglycan in cell wall.
  3. Activate autolytic enzymes.
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3
Q

Penicillin G,V clinical use

A
  1. ​Mostly used for gram-positive organisms
    1. S. pneumoniae
    2. S. pyogenes
    3. Actinomyces
  2. Gram negative cocci
    1. N. meningitidis
  3. Spirochetes
    1. T. pallidum

Bactericidal for gram-positive cocci, gram-positive rods, gram-negative cocci, and spirochetes.

Penicillinase sensitive.

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4
Q

Penicillin G, V toxicity

A
  • Hypersensitivity reactions
  • Hemolytic anemia
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5
Q

Penicillin G, V resistance

A

Penicillinase in bacteria (a type of β-lactamase) cleaves β-lactam ring.

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6
Q

Aminopenicillins

A
  • ​amoxicillin
  • ampicllin

Penicillinase-sensitive penicillins

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7
Q

Aminopenicillin mechanism

(and bioavailability)

A
  • Same as penicillin → wider spectrum,
  • Penicillinase sensitive.
  • Also combine with clavulanic acid to protect against destruction by β-lactamase.

(amoxicillin and ampicillin)

Note that amoxicillin has greater oral bioavailability than ampicllin.

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8
Q

Aminopenicillin clinical use

A

Exteneded spectrum penicillin

  1. H. influenzae (gram negative)
  2. H. pylori (gram negative, oxidase positive, comma shaped)
  3. E. coli (gram negative rod)
  4. Listeria monocytogenes (gram positive rod)
  5. Proteus mirabilis (gram negative rod)
  6. Salmonella (gram negative rod)
  7. Shigella (gram negative rod)
  8. enterococci (gram positive cocci)
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9
Q

Aminopenicillin toxicity

A
  • hypersensitivity reactions
  • rash
  • pseudomembranous colitis (ie C. dif, a gram positive rod)
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10
Q

Aminopenicillin resistance

A

Penicillinase in bacteria (a type of β-lactamase) cleaves β-lactam ring.

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11
Q

Penicillinase-resistant penicillins

A
  1. Dicloxacillin
  2. Nafcillin
  3. Oxacillin
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12
Q

Penicillinase resistant penicillins mechanism

A

(dicloxacillin, nafcillin, oxacillin)

Same as penicillin → narrow spectrum.

Penicillinase resistant because bulky R group blocks access of β-lactamase to β-lactam ring.

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13
Q

Penicillinase resistant penicillins clinical use

A

(dicloxacillin, nafcillin, oxacillin)

S. aureus (except MRSA; resistant because of altered penicillin-binding protein target site).

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14
Q

Penicillinase resistant penicillins toxicity

A
  • Hypersensitivity reactions
  • interstitial nephritis
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15
Q

Antipseudomonals

A
  • Piperacillin
  • Ticarcillin
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16
Q

Antipseudomonal mechanism

A

(piperacillin, ticarcillin)

Same as penicillin. Extended spectrum.

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17
Q

Antipseudomonal clinical use

A

(piperacillin, ticarcillin)

Pseudomonas spp. and other gram-negative rods.

Susceptible to penicillinase; use with β-lactamase inhibitors.

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18
Q

Antipseudomonal toxicity

A

(piperacillin, ticarcillin)

Hypersensitivity reactions.

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19
Q

Beta lactamase inhibitors

A
  1. Clavulanic Acid
  2. Sulbactam
  3. Tazobactam

Often added to penicillin antibiotics to protect the antibiotic from destruction by β-lactamase (penicillinase).

20
Q

Cephalosporins (generations 1-4) mechanism

[and what don’t they cover]

A

β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases. Bactericidal.

Organisms typically not covered by cephalosporins are LAME:

  • Listeria
  • Atypicals (Chlamydia, Mycoplasma)
  • MRSA
  • Enterococci

Exception: ceftaroline covers MRSA.

21
Q

First generation cephalosporins

A
  1. Cefazolin (IV)
  2. cephalexin (oral)
22
Q

First generation cephalosporin clinical use

A

1st generation (cefazolin, cephalexin)—

  1. gram-positive cocci
  2. gram-negative rods
    1. Proteus mirabilis
    2. E. coli
    3. Klebsiella pneumoniae

Cefazolin used prior to surgery to prevent S. aureus wound infections.

23
Q

Second generation cephalosporins

A
  1. cefoxitin (IV)
  2. cefaclor
  3. cefuroxime
24
Q

Second generation cephalosporin clinical use

A

2nd generation (cefoxitin, cefaclor, cefuroxime)—

  1. gram-positive cocci
  2. Haemophilus influenzae
  3. Enterobacter aerogenes
  4. Neisseria spp.
  5. Proteus mirabilis
  6. E. coli
  7. Klebsiella pneumoniae
  8. Serratia marcescens
25
Q

Third generation cephalosporins

A
  1. ceftriaxone
  2. cefotaxime
  3. ceftazidime
26
Q

Third generation cephalosporin clinical use

A

3rd generation (ceftriaxone, cefotaxime, ceftazidime)—serious gram-negative infections resistant to other β-lactams.

Ceftriaxone—meningitis, gonorrhea, disseminated Lyme disease (borrelia).

Ceftazidime—Pseudomonas

27
Q

Fourth generation cephalosporins

A

cefepime

28
Q

Fourth generation cephalosporin clinical use

A

4th generation (cefepime)—

gram-negative organisms

with ↑ activity against Pseudomonas and gram-positive organisms.

29
Q

Fifth generation cephalosporins

A

Ceftaroline

30
Q

Fifth generation cephalosporin clinical use

A

5th generation (ceftaroline)— broad gram-positive and gram-negative organism coverage, including MRSA.

Does not cover Pseudomonas.

31
Q

Cephalosporin toxicity

A
  1. hypersensitivity reactions
  2. autoimmune hemolytic anemia
  3. disulfiram-like reaction
  4. vitamin K deficiency
  5. Exhibit cross-reactivity with penicillins, ↑ nephrotoxicity of aminoglycosides.
32
Q

Cephalosporin resistance

A

Structural change in penicillin-binding proteins (transpeptidases).

33
Q

Carbapenems

A
  1. imipenem
  2. meropenem
  3. ertapenem (limited Pseudomonas coverage)
  4. doripenem
34
Q

Carbapenem mechanism

A

Imipenem is a broad-spectrum, β-lactamase–resistant carbapenem. Always administered with cilastatin (inhibitor of renal dehydropeptidase I) to ↓ inactivation of drug in renal tubules.

35
Q

Carbapenem clnical use

A

(imipenem, meropenem, ertapenem, doripenem)

  • ​Gram-positive cocci
  • Gram-negative rods
  • Anaerobes

Wide spectrum, but significant side effects limit use to life-threatening infections or after other drugs have failed.

Meropenem has a ↓ risk of seizures and is stable to dehydropeptidase I.

36
Q

Carbapenem toxicity

A
  • GI distress
  • skin rash
  • CNS toxicity (seizures) at high plasma levels
37
Q

Monobactams

A

Aztreonam

38
Q

Monobactam mechanism

A

Prevents peptidoglycan cross-linking by binding to penicillin- binding protein 3.

  • Less susceptible to β-lactamases.
  • Synergistic with aminoglycosides.
  • No cross-allergenicity with penicillins.
39
Q

Monobactam clinical use

A

Gram-negative rods only—no activity against gram-positives or anaerobes.

For penicillin-allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides.

40
Q

Monobactam toxicity

A

Usually nontoxic; occasional GI upset.

41
Q

Glycopeptides

A
  • Bacitracin
  • Vancomycin
42
Q

Vancomycin mechanism

A

Inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors.

Bactericidal. Not susceptible to β-lactamases.

43
Q

Vancomycin clinical use

A

Gram-positive bugs only—serious, multidrug-resistant organisms, including

  • MRSA
  • S. epidermidis
  • sensitive Enteroccocus species
  • Clostridium difficile (oral dose for pseudomembranous colitis)
44
Q

Vancomycin toxicity

A

Well tolerated in general—but NOT trouble free.

  1. Nephrotoxicity
  2. Ototoxicity
  3. Thrombophlebitis
  4. diffuse flushing—red man syndrome (can largely prevent by pretreatment with antihistamines and slow infusion rate)
45
Q

Vancomycin resistance

A

Occurs in bacteria via amino acid modification of D-ala D-ala to D-ala D-lac.