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Antimicrobials - Cell wall synthesis inhibitors Flashcards

1
Q

What are lactam antibiotics?

A

a group of antibiotics that inhibit cell wall synthesis, and are thus all -cidal; includes: penicillins, cephalosporins, imipenem/meropenem, aztreonam

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2
Q

Which cell wall synthesis inhibitor is not a lactam?

A

vancomycin

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3
Q

What are the 3 mechanisms of resistance against penicillins and cephalosporins?

A
  1. β-lactamases
  2. Change in PBPs
  3. Change in porins (in G- bacteria only e.g. pseudomonas)
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4
Q

What is one of the only bacteria that have not developed resistance to narrow spectrum penicillins (β-lactamase sensitive; G and V)? What form of penicillin is often given to patients infected with this bacteria?

A 
Treponema pallidum (Syphilis)
Benzathine penicillin given as a depot (slow-releasing IM injection)
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5
Q

What is the primary use of very narrow spectrum penicillins (β-lactamase resistant; methicillin, nafcillin, oxacillins)?

A

S. aureus (non-MRSA)

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6
Q

After the development of MRSA, what was the next approach with penicillin development?

A

forget about the β-lactamase resistance approach and go for drugs that will get through the pore of G- bacteria → broad spectrum penicillins such as amoxicillin and ampicillin

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7
Q

What do broad spectrum penicillins (eg. ampicillin) work on?

A

Very well on:

  1. G+ cocci except staph
  2. G+ rods s.a. listeria
  3. G- bugs (large variety including H. pylori, H. flu, E. coli)
  4. Borrelia (lyme)
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8
Q

What is the main bacteria that extended spectrum penicillins (β-lactamase sensitive; ticarcillin, piperacillin, azlocillin, carbenicillin) used for?

A

pseudomonas

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9
Q

What are the main side effects of cephalosporins?

A

Similar to all lactams:

  1. hypersensitivity
  2. GI distress (kills gut flora)
  3. Disulfaram-like effect (those with an azo group like cefoperAZOne)
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10
Q

If a patient has allergies to lactams, what is an alternative treatment?

A

macrolides (esp. for G+) or aztreonam (ONLY if G- rod e.g. pseudomonas)

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11
Q

What is the main way that penicillins are eliminated from the body?

A

all are eliminated by active tubular secretion from the kidney except nafcillin and oxacillin

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12
Q

How are nafcillin and oxacillin eliminated?

A

in bile

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13
Q

Which penicillins would require dose adjustment in renal impairment? In liver dysfunction?

A

Renal impairment: all penicillins except naficillin and oxacillin which would need to be adjusted in liver dysfunction

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14
Q

Which penicillins are given as IV drugs?

A

extended spectrum for pseudomonas (ticarcillin, piperacillin, carbenicillin, etc)

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15
Q

What are the 3 main side effects of penicillins?

A
  1. Hypersensitivity (types I - IV possible)
  2. GI distress (kills gut flora, esp. ampicillin which doesn’t get absorbed as well as amoxicillin)
  3. Jarisch-Herxheimer reaction (in tx of syphilis, destruction of cell wall → release of antigens → fever, joint pain)
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16
Q

What is the cause and result of C. diff infection in the gut? How do you treat it?

A

antibiotics, especially ampicillin → c. diff takeover → pseudomembranous colitis → metronidazole

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17
Q

Any cephalosporin with a “ph” in the name is what generation? What drug in this generation does not have a “ph”?

A

1st - cefazolin is the only 1st generation with an “f”

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18
Q

Why is cefazolin used as a prophylactic drug in surgery?

A
  1. it has a long T1/2: 24 hr
  2. covers gram positive skin microbes like staph and strep
  3. covers some gram negatives like E. coli if doing GI surgery
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19
Q

What are the 2 main advantages of 2nd generation cephalosporins over 1st generation?

A
  1. better gram negative coverage

2. cross BBB

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20
Q

Which was the first cephalosporin to cross the BBB? What generation is this?

A

cefuroxime - 2nd gen

21
Q

Which 2nd generation cephalosporin causes a disulfaram-like reaction? Name a 3rd gen. which causes this reaction.

A

cefotetan; cefoperazone

22
Q

What advancements came with the 3rd generation of cephalosporins?

A

very wide spectrum of action - can be used in the empirical management of sepsis and meningitis

23
Q

What are the resistance mechanisms against cephalosporins?

A

Same as penicillin:

  1. β-lactamases
  2. Change in PBPs
  3. Change in porins (in G- bacteria only)
24
Q

What do 3rd generation cephalosporins NOT cover? What would you use instead for these bugs?

A 
LAME!
Listeria (use amoxicillin)
Atypicals (use macrolides/tetracycline)
MRSA (use vancomycin)
Enterococci (use amoxicillins in combo with aminoglycosides)
25
Q

Why don’t β lactam antibiotics like penicillin and cephalosporin work on atypicals? What should be used instead?

A

these drugs are cell wall synthesis inhibitors and atypicals either have no cell wall, funky cell walls, or live intracellularly; use protein synthesis inhibitors like macrolides or tetracycline

26
Q

What is a fourth generation cephalosporin and how is it delivered? What is the advantage?

A

cefepime, by IV; β-lactamase resistant and like 3rd gen. very wide spectrum

27
Q

Like most penicillins, cephalosporins are renally cleared and dosage must be modified in renal patients. Also like penicillins, there are two cephalosporins that are eliminated in bile. What are they? What are the penicillin equivalents?

A

cefoperazone and ceftriaxone;

nafcillin and oxacillin

28
Q

List all the main classes of cell wall synthesis inhibitors. Which is not a lactam?

A
  1. penicillins
  2. cephalosporins
  3. imipenem/meropenem
  4. aztreonam
  5. vancomycin - non-lactam
    (note that the mechanism is the same for all lactams)
29
Q

What are the main side effects of cephalosporins?

A

Similar to penicillins:

  1. hypersensitivity
  2. GI distress (kills gut flora)
  3. Disulfaram-like effect (those with an azo group like cefoperAZOne)
30
Q

If a patient has allergies to lactams, what is an alternative treatment?

A

macrolides (esp. for G+) or aztreonam (ONLY if G- rod e.g. pseudomonas)

31
Q

Which lactams are delivered IV for life-threatening nosocomial conditions?

A

imipenem and meropenem

32
Q

What is the advantage to using imipenem and meropenem?

A

β-lactamase resistant and very broad spectrum (but don’t cover MRSA)

33
Q

What are the most potent lactams?

A

imipenem and meropenem

34
Q

Why must cilastatin be given with imipenem?

A

prevents imipenem from being metabolized too quickly by the kidney (inhibits dehydropeptidase); if not given together, imipenem would be useless

35
Q

What is the major side effect of imipenem?

A

50% of patients given this drug will experience seizures

36
Q

As lactams, what do we know already about the side effects and pharmacokinetics of imipenem and meropenem?

A 
Side effects include:
1. hypersensitivity 
2. GI distress
3. drug fever due to hypersensitivity
Pharmacokinetics:
- eliminated by kidneys so must be dose adjusted in renal patients
37
Q

What similarities does aztreonam have to imipenem and meropenem?

A
  • used IV
  • resistant to β-lactamases
  • same mechanism of action as penicillins/cephalosporins
38
Q

What is aztreonam used for?

A

Only effective for G- rods (because it only binds to PBPs in G- rods)

39
Q

Despite aztreonam’s narrow spectrum of action (G- rods only) and limited use as an IV drug, what is the benefit of this drug?

A

no cross allergenicity with penicillins and cephalosporins

40
Q

How is vancomycin different than lactams?

A
  1. binding site: instead of PBP → D-ala-D-ala muramyl pentapeptide
  2. inhibitive action: instead of transpeptidation → transglycosylation (in elongation of peptidoglycan chain)
41
Q

What are 3 indications for vancomycin?

A
  1. MRSA
  2. enterococci
  3. C. diff (only if metronidazole doesn’t work – we are reserving vanc. for MRSA)
42
Q

How is vancomycin administered? What about in the case of C. diff?

A

IV - break open bag and drink to treat C. diff (not absorbed)

43
Q

How does VRE evade vancomycin?

A

altered binding site: D-ala-D-ala → D-ala-D-lac

44
Q

What drugs can be used for VRE and VRSA?

A

Linezolid or Streptogramins

45
Q

Does vancomycin cross the BBB?

A

no

46
Q

Pharmacokinetics of vanc in terms of half life and elimination route?

A

eliminated by kidneys

long T1/2

47
Q

Toxicities of vanc:

A
  1. hypersensitivity - Type I → histamine release → vasodilation/anaphylaxis → red man syndrome
  2. ototoxicity - severe, causes deafness
  3. nephrotoxic - mostly a problem additively w/ other nephrotoxic drugs
48
Q

List all the main classes of cell wall synthesis inhibitors. Which is not a lactam?

A
  1. penicillins
  2. cephalosporins
  3. imipenem/meropenem
  4. aztreonam
  5. vancomycin - non-lactam (note that the mechanism is the same for all lactams)

My Notes (23 decks)

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