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ACEM Primary Written > Infectious diseases: Pharmacology - Beta lactams > Flashcards

Infectious diseases: Pharmacology - Beta lactams Flashcards

1
Q

Five types of beta lactams and examples

A
  1. Penicillins (e.g. benzylpenicillin, ampicillin)
  2. Cephalosporins (e.g. cefotaxime, cefaclor)
  3. Monobactams (e.g. aztreonam)
  4. Carbapenems (e.g. meropenem, ertapenem)
  5. B-lactamase inhibitors (e.g. tazobactam, clavulanate)
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2
Q

Mechanism of action of penicillins

A

Bind penicillin-binding proteins to prevent transpeptidation reaction essential to cross-linking and therefore stability of bacterial wall
This leads to cell lysis via unknown mechanisms

Bactericidal only when bacteria actively growing and synthesising cell wall

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3
Q

Four mechanisms of resistance to beta lactams. Which of these is most common?

A
  1. Inactivation by beta-lactamase (most common)
  2. Modification of target PBPs
  3. Decreased antibiotic penetration
  4. Antibiotic efflux
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4
Q

What is the mechanism of methicillin resistance in MRSA? What other examples of resistance share this mechanism?

A

Modification of target PBPs
Also occurs in pneumococci and enterococci resistance to penicillin

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5
Q

What types of bacteria may develop resistance by decreasing penetration of antibiotic or via antibiotic efflux?

A

Gram negatives, as these are the only bacteria with an outer cell membrane

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6
Q

Three classifications of penicillins and examples

A
  1. Natural penicillins (e.g. benzylpenicillin - penicillin G, phenoxymethylpenicillin - penicillin V)
  2. Antistaphylococcal (e.g. flucloxacillin, dicloxacillin, methicillin)
  3. Extended spectrum (e.g. ampicillin/amoxicillin, piperacillin, ticarcillin)
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7
Q

Describe the difference in antimicrobial coverage afford by natural, antistaphylococcal, and extended spectrum penicillins

A

Natural: Gram positives, GNCs, non-B-lactamase-producing anaerobes
Antistaphylococcal: staphylococci, streptococci
Extended spectrum: Gram positives, Gram negatives, antipseudomonal (except amoxicillin/ampicillin)

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8
Q

What group of bacteria is not covered by natural penicillins?

A

GNRs

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9
Q

What group of bacteria is not covered by antistaphylococcal penicillins?

A

Gram negatives, anaerobes, enterococci

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10
Q

Which of the various classifications of penicillins are B-lactamase susceptible vs resistant?

A

B-lactamase susceptible: natural and extended spectrum penicillins
B-lactamase resistant: antistaphylococcal

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11
Q

Describe the absorption of penicillins

A

Dicloxacillin, amoxicillin and ampicillin are acid-stable and well-absorbed orally (but with exception of amoxicillin are impaired by food)
Rest can be given IM or IV: IV preferred as IM causes pain and local irritation
Benzathine or procaine can be added to IM preparations to delay absorption and prolong duration of action

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12
Q

Describe the distribution of penicillins

A

Widely distributed in body fluids and tissues with exception of eye, prostate and CNS
Highly polar so extracellular > intracellular concentrations

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13
Q

Describe the excretion of penicillins

A

Natural penicillins rapidly excreted by kidneys (90% by tubular secretion; requires dose adjustment in renal failure)
Others less rapidly
Nafcillin primarily biliary excretion
Dicloxacillin both biliary and renal excretion (does not require dose adjustment)

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14
Q

Nine microbial indications for natural penicillins

A
  1. Streptococci
  2. Staphylococci
  3. Enterococci
  4. Meningococci
  5. Penicillin-susceptible pneumococci
  6. Treponema pallidum (and other spirochetes)
  7. Clostridium
  8. Actinomyces
  9. Others non-B-lactamase producing GPRs and anaerobes
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15
Q

Two microbial indications for antistaphylococcal penicillins

A
  1. B-lactamase-producing Staphylococci
  2. Penicillin-susceptible streptococci and pneumococci
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16
Q

Indications for extended spectrum penicillins

A

Gram negatives
Can be used in combination with B-lactamase inhibitors (e.g. tazobactam, clavulanate) to broaden coverage

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17
Q

What % of staphyloccocal strains produce B-lactamase? What other two microbes are increasingly producing B-lactamase?

A

90%
Also produced increasingly by H. influenzae and N. gonorrhoae

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18
Q

What is the major adverse effect seen with penicillins?

A

Hypersensitivity: anaphylaxis or serum sickness

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19
Q

Two specific risks of ampicillin

A
  1. Pseudomembranous colitis
  2. Non-allergic rash (especially when given in setting of viral infection e.g. EBV)
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20
Q

Specific risk of methicillin

A

Interstitial nephritis

21
Q

Specific risk of nafcillin

A

Neutropenia

22
Q

Describe the general difference in coverage offered by different generations of cephalosporins

A

First generation offers good Gram positive cover
Increasing Gram negative cover with second and third generation
Fourth generation covers both Gram positive and negative (including Pseudomonas)

23
Q

What is the difference in activity between penicillins and cephalosporins?

A

Cephalosporins less susceptible to B-lactamase

24
Q

Two organisms against which cephalosporins are not active

A
  1. Enterococcus
  2. Listeria monocytogenes
25
Q

Two examples of first generation cephalosporins

A

Cephalexin
Cephazolin

26
Q

Three examples of second generation cephalosporins

A

Cefuroxime
Cefaclor
Cefotetan (actually a cephamycin)

27
Q

Three examples of third generation cephalosporins

A

Ceftriaxone
Cefotaxime
Ceftazidime

28
Q

One example of fourth generation cephalosporins

A

Cefepime

29
Q

One example of a cephamycin. What generation of cephalosporin does this fall under?

A

Cefotetan

30
Q

Coverage of first generation cephalosporins

A

GPC except MRSA
Limited Gram negatives: E. coli, Klebsiella, Proteus
Some anaerobic cocci

31
Q

Coverage of second generation cephalosporins

A

Extended Gram negative compared with first gen: Klebsiella, H. influenzae)
Cefotetan offers anaerobe coverage
Some Gram positives

32
Q

Coverage of third generation cephalosporins

A

Expanded Gram negative compared with first and second gen: Citrobacter, Serratia, B-lactamase-producing Haemophilus and Neisseria)

33
Q

Coverage of fourth generation cephalosporins

A

More resistant to enterobacter B-lactamase and some extended spectrum B-lactamase
Pseudomonas cover

34
Q

Indications for first generation cephalosporins

A

Cephalexin: simple UTI or cellulitis (not multiorganism)
Cephazolin: surgical prophylaxis

35
Q

Indications for second generation cephalosporins

A

Sinusitis, otitis, LRTI due to activity against B-lactamase-producing H. influenzae and M. catarrhalis
Cefotetan: peritonitis, diverticulitis (mixed anaerobes)
Cefuroxime: CAP

36
Q

Indications for third generation cephalosporins (specific for ceftazidime and ceftriaxone)

A

Ceftazidime: Pseudomonas
Ceftriaxone: gonorrhoea (due to increasing penicillin resistance), meningitis where penicillin-resistant pneumococci is suspected, sepsis of unknown cause

37
Q

Indications for fourth generation cephalosporins

A

As for third gen but increased activity against penicillin-resistant streptococci and enterobacter

38
Q

Which cephalosporins cross the BBB?

A

Some third gen (e.g. ceftriaxone)

39
Q

What meningitis-causing organisms will not be covered by ceftriaxone and what other antibiotics should be considered instead?

A

Listeria monocytogenes (needs ampicillin or benzylpenicillin)
Pseudomonas (needs aminoglycoside)
Highly resistant pneumococcal strains (needs vancomycin)

40
Q

Four possible adverse effects of cephalosporins. Which of these are specific to cefotetan?

A
  1. Hypersensitivity (5-10% cross-reactivity with penicillins)
  2. Superinfection
  3. Toxicity*
  4. Disulfaram-like reaction (EtOH sensitivity)*
  • specific to cefotetan
41
Q

What is the mechanism of superinfection in the setting of cephalosporin use?

A

2nd/3rd gen cephalosporins have limited activity against Gram positives
Leads to superinfection with e.g. MRSA, enterococcus

42
Q

What are the four features of cefotetan toxicity?

A
  1. Local irritation
  2. Renal toxicity
  3. Hypoprothrombinaemia (increased bleeding risk)
43
Q

Three examples of beta lactamase inhibitors

A

Clavulanate
Tazobactam
Sulbactam

44
Q

Give four examples of bacteria which produce C class B-lactamases not easily inhibited by beta lactamase inhibitors

A

Enterobacter
Citrobacter
Serratia marscenens
Pseudomonas

45
Q

Carbapenem coverage

A

Good activity against most GNRs including Pseudomonas (except for ertapenem)
Resistant to most beta lactamases

46
Q

Does carbapenem dosing need to be renally adjusted?

A

Yes

47
Q

Indications for use of carbapenems

A

Multiresistant organisms including ESBL
Mixed aerobic/anaerobic infections

48
Q

Which is more cross-reactive with penicillins: cephalosporins or carbapenems?

A

Cephalosporins (5-10%) > carbapenems (1%)

ACEM Primary Written (150 decks)

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