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Antibiotics > Beta-Lactams Questions > Flashcards

Beta-Lactams Questions Flashcards

1
Q

What classes of drugs make up beta-lactams?

A
  • penicillins
  • cephalosporins
  • carbapenems
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2
Q

How are monobactams different than beta-lactams?

A
  • structurally similar but lack one of the two rings that other beta-lactams have
  • have little to no cross-allergenicity with other beta-lactams
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3
Q

What do all beta-lactams have in common?

A
  • can cause hypersensitivity reactions
  • seizures can result from very high doses of any beta-lactam (and some cause other neurologic effects)
  • share a mechanism of action
  • lack activity against atypical organisms
  • all (except one cephalosporin) lack activity against MRSA
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4
Q

Describe a beta-lactam hypersensitivity reaction.

A

Ranges from:

  • mild rashes
  • drug fever
  • acute interstitial nephritis (AIN)
  • anaphylaxis
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5
Q

What is responsible for cross-sensitivity between classes of beta-lactams?

A

Similarities between side chains

  • likelihood of allergic reactions can be predicted by side chains
  • cross-sensitivity seems to be lower than previously thought
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6
Q

Do beta-lactams need to be adjusted for a patient’s renal function?

A

Yes

-if dose not adjusted, accumulation to toxic levels can occur (seizures)

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7
Q

Describe the MOA of beta-lactams.

A

Inhibition of transpeptidases (penicillin-binding proteins) in the bacterial cell wall

Inhibit cross-linking of peptidoglycan in the cell wall (leading to autolysis and cell death)

-giving two beta-lactams in combination for the same infection is generally not useful (but also not antagonistic)

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8
Q

What class of organisms do beta-lactams lack activity against?

A

Atypical organisms (such as):

  • Mycoplasma pneumoniae
  • Chlamydophila pneumoniae

-add another drug to the regimen if these organisms suspected (as in community-acquired pneumonia)

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9
Q

What specific organism do beta-lactams lack activity against?

A

MRSA

  • add vancomycin or another drug if this organism suspected
  • only exception is ceftaroline (cephalosporin)
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10
Q

What is the half life of penicillins?

A

Very short half lives (<2 hours)

  • must be dosed multiple times per day
  • half lives of most penicillins are prolonged in renal dysfunction
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11
Q

What is a severe reaction of penicillins?

A

Hypersensitivity reactions

  • if a patient has a true IgE-mediated hypersensitivity reaction, avoid other penicillins
  • if reaction not severe, may use cephalosporins or carbapenems
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12
Q

Describe the absorption of of penicillins.

A

Many are relatively poorly absorbed

  • this can lead to diarrhea when oral therapy is needed
  • often a conversion from IV to PO means there will be a substantial decrease in the amount of act or drug in the body
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13
Q

Describe penicillin research development.

A

Development focused on either:

  • improved activity against staphylococci (MSSA)
  • or GNRs

Then beta-lactamase inhibitors were discovered

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14
Q

Name the natural penicillins.

A
  • penicillin G

- penicillin V

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15
Q

What organisms do natural penicillins have GOOD activity against?

A
  • Treponema pallidum

- most streptococci (including S. pneumoniae)

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16
Q

What organisms do natural penicillins have MODERATE activity against?

A

-enterococci

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17
Q

What organisms do natural penicillins have POOR activity against?

A

-almost everything else

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18
Q

How do the adverse effects of natural penicillins compare to other beta-lactams?

A

Similar to those of other beta-lactams

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19
Q

What is the half life of natural penicillins?

A

Very short half life

  • must be dosed frequently or given by continuous infusion
  • other more conveniently dosed narrow spectrum beta-lactams are available for most organisms treatable with penicillin
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20
Q

Describe long acting depot formulations of natural penicillin.

A

Procaine / Benzathine

  • given IM
  • doses vary considerably
  • giving them IV can be fatal
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21
Q

What are the dosage forms of natural penicillins?

A
  • penicillin V is the oral form

- penicillin G is the IV form

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22
Q

What is the drug of choice for syphilis?

A

Penicillin G

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23
Q

Is penicillin a GOOD empiric choice for most infections?

A

No, it is a POOR empiric choice because of resistance

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24
Q

The IV penicillin breakpoints for S. pneumoniae were redefined in 2008 by CLSI (lowered the percentage of S. pneumoniae isolates considered resistant to penicillin considerably. What are the caveats?

A
  • only applies to IV penicillin
  • does not apply to CNS infections (old breakpoints remain in effect)
  • breakpoints are useful predictors of treatment success (but are not always set correctly)
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25
Q

What are natural penicillins good for?

A
  • syphilis (particularly neurosyphilis)

- also used in susceptible streptococcal infections (ex: pharyngitis, endocarditis)

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26
Q

Name the antistaphylococcal penicillins?

A
  • Nafcillin
  • Oxacillin
  • Dicloxacillin
  • methicillin
  • cloxacillin
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27
Q

Antistaphylococcal penicillins are resistant to penicillinases. However, like natural penicillins, what organisms are they not effective against?

A

Have poor gram negative activity like natural penicillins

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28
Q

What organisms do antistaphylococcal penicillins have GOOD activity against?

A
  • MSSA

- streptococci

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29
Q

What organisms do antistaphylococcal penicillins have POOR activity against?

A
  • GNRs
  • enterococci
  • anaerobes
  • MRSA
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30
Q

How do the adverse effects of antistaphylococcal penicillins compare to other beta-lactams?

A

Similar

-possibly higher incidence of AIN

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31
Q

What is the half life of antistaphylococcal penicillins?

A
  • short half life
  • must be dosed frequently
  • cause phlebitis
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32
Q

Why may a first generation cephalosporin be a better option than an antistaphylococcal penicillin in most patients?

A
  • less risk of phlebitis
  • easier to administer
  • better tolerated
  • good choice for most patients
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33
Q

How are antistaphylococcal penicillins eliminated?

A

Eliminated from the body in large part by the LIVER

-do NOT need to be adjusted in cases of renal dysfunction

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34
Q

Are antistaphylococcal penicillins interchangeable with each other?

A

YES

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35
Q

What drugs are the standard tests for antistaphylococcal penicillin susceptibility usually done with?

A
  • oxacillin

- cefoxitin

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36
Q

What are antistaphylococcal penicillins good for?

A

Infections caused by MSSA; ex:

  • endocarditis
  • skin and soft tissue infections
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37
Q

Do beta-lactams or vancomycin kill staphylococci more quickly?

A

Beta-lactams

  • patients with an MSSA infection who lack a serious beta-lactam allergy should be switched to a beta-lactam
  • has been shown to be an important difference in serious infections
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38
Q

Name the aminopenicillins.

A
  • amoxicillin

- ampicillin

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39
Q

Why do aminopenicillins have better gram negative coverage compared to previous classes of penicillins?

A

More water-soluble (pass through porin channels in the cell wall of some gram negative organisms)

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40
Q

Are aminopenicillins active against staphylococci?

A

Rarely; they almost always produce penicillinases

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41
Q

What organisms do aminopenicillins have GOOD activity against?

A
  • streptococci

- enterococci

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42
Q

What organisms do aminopenicillins have MODERATE activity against?

A
  • enteric GNRs

- Haemophilus

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43
Q

What organisms do aminopenicillins have POOR activity against?

A
  • staphylococci
  • anaerobes
  • Pseudomonas
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44
Q

How do the adverse effects of aminopenicillins compare to other beta-lactams?

A

Similar

-have high incidence of diarrhea when given orally

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45
Q

Which aminopenicillin is a better choice for oral therapy?

A

Amoxicillin

  • more bioavailable
  • better tolerated
  • administered less frequently

Use ampicillin for IV therapy

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46
Q

What is a drug of choice for susceptible enterococci?

A

Ampicillin

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47
Q

Which species of enterococci is almost always susceptible to ampicillin?

A

Enterococcus faecalis

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48
Q

Which species of enterococci is almost often resistant to ampicillin?

A

Enterococcus faecium

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49
Q

Why are aminopenicillins often listed as alternative regimens for UTIs in pregnant women?

A
  • pregnancy category B

- eliminated renally

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50
Q

What are some precautions when using aminopenicillins in pregnant women for UTIs?

A
  • resistance to Escherichia coli is very high

- susceptibility testing should be performed

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51
Q

Why should follow-up cultures always be performed in pregnant women with UTIs?

A

Even asymptomatic bacteruria is dangerous for them

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52
Q

What are aminopenicillins good for?

A

Infections caused by susceptible:

  • GNRs
  • enterococci
  • streptococci
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53
Q

Why are aminopenicillins used only infrequently in complicated nosocomial infections?

A

Because resistance among GNRs is prevalent

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54
Q

What is amoxicillin frequently prescribed for?

A

Infections of the upper respiratory tract; ex:

  • streptococcal pharyngitis (strep throat)
  • otitis media (ear infection)
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55
Q

How is bactericidal activity achieved against enterococci?

A

Combining ampicillin (or any other beta-lactam) with an aminoglycoside

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56
Q

When should a bactericidal antibiotic regimen be considered against enterococci?

A

Serious infections; ex:

-endocarditis

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57
Q

Name the antipseudomonal penicillins.

A
  • piperacillin
  • ticarcillin

Commonly used now with a beta-lactamase inhibitor

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58
Q

Are the antipseudomonal penicillins active against staphylococci?

A

NO

  • just as susceptible to beta-lactamases as amoxicillin and ampicillin
  • strains of GNRs that produce beta-lactamases are also resistant
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59
Q

What organisms do antipseudomonal penicillins have GOOD activity against?

A
  • P. aeruginosa
  • streptococci
  • enterococci
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60
Q

What organisms do antipseudomonal penicillins have MODERATE activity against?

A
  • enteric GNRs

- Haemophilus

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61
Q

What organisms do antipseudomonal penicillins have POOR activity against?

A
  • staphylococci

- anaerobes

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62
Q

How do the adverse effects of antipseudomonal penicillins compare to other beta-lactams?

A

Similar

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63
Q

Name the penicillin/beta-lactamase inhibitor combinations.

A
  • ampicillin/sulbactam
  • amoxicillin/clavulanate
  • piperacillin/tazobactam
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64
Q

What is the MOA of beta-lactamase inhibitors?

A
  • counter beta-lactamases
  • mimic the structure of beta-lactams
  • have little antimicrobial activity on their own
  • bind to beta-lactamases IRREVERSIBLY (preventing the beta-lactamase from destroying any beta-lactams that are co-administered
  • beta-lactamase inhibitors structurally resemble beta-lactams and bind to many beta-lactamases (rendering them unable to inactivate the coadministered beta-lactam)
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65
Q

Do beta-lactamase inhibitors enhance the activity of beta-lactams?

A

No

  • they only free up the beta-lactam to kill the organism that it has intrinsic activity against
  • they restore activity; not add to it
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66
Q

What organisms do penicillin/beta-lactamase inhibitor combinations have GOOD activity against?

A
  • MSSA
  • streptococci
  • enterococci
  • many anaerobes
  • enteric GNRs
  • P. aeruginosa (only piperacillin/tazobactam)
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67
Q

What organisms do penicillin/beta-lactamase inhibitor combinations have MODERATE activity against?

A

-GNRs with advanced beta-lactamases

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68
Q

What organisms do penicillin/beta-lactamase inhibitor combinations have POOR activity against?

A
  • MRSA

- ESBL (extended-spectrum beta-lactamase) producing GNRs

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69
Q

How do the adverse effects of penicillin/beta-lactamase inhibitor combinations compare to other beta-lactams?

A

Similar

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70
Q

Which beta-lactamase inhibitor combination is available orally?

A

Amoxicillin/clavulanate

-higher doses associated with more diarrhea

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71
Q

Dose the dose of clavulanate change for different doses of oral amoxicillin?

A

NO

Fixed dose of 125mg

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72
Q

Are beta-lactamase inhibitors effective against all beta-lactamases?

A

NO

-new beta-lactamases are continually being discovered and are becoming more prevalent

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73
Q

Are beta-lactamase inhibitors available outside of the combination products?

A

No

-except for study purposes

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74
Q

What beta-lactamase inhibitor has useful antimicrobial activity?

A

Sulbactam

  • against Acinetobacter baumannii (highly drug resistant GNR that causes nosocomial infections)
  • high doses of ampicillin/sulbactam can be used for treatment
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75
Q

Which beta-lactamase inhibitor is more potent at inhibiting beta-lactamases?

A

Clavulanate

-higher doses of sulbactam are given to account for this

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76
Q

How do the spectra of amoxicillin/clavulanate and ampicillin/sulbactam compare?

A

Nearly identical

-differences in susceptibility testing may be due to the low concentrations of sulbactam used in tests

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77
Q

What are penicillin/beta-lactamase inhibitor combinations good for?

A

-empiric therapy of nosocomial infections, particularly nosocomial pneumonia (not aminopenicillin based combinations)

Good empiric choice for mixed infections (have activity against aerobes and anaerobes); ex:

  • intra-abdominal infections
  • diabetic ulcers
  • aspiration pneumonia
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78
Q

When is amoxicillin/clavulanate used?

A

Upper and lower respiratory tract infections

-when beta-lactamase producing organisms are found/suspected

Can also be used for UTIs when resistance to other drugs is seen

-should not be given for a short 3 day course (such as FQ or TMP/SMX)

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79
Q

Are penicillin/beta-lactamase inhibitor combinations good for empiric or definitive therapy?

A

Empiric

-poor choice for definitive therapy if alternatives available

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80
Q

What do all cephalosporins have in common?

A
  • have some cross-allergenicity with penicillins

- generally more resistant to beta-lactamases than penicillins are

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81
Q

What is the likelihood of cross-reactivity between penicillin and cephalosporin allergies?

A
  • oft-quoted 10%
  • reasonable estimate is no more than 3-5%
  • some publications support even lower numbers (particularly for later-generation agents)
  • evidence suggests that similar side chains are the reason for cross-reactivity
  • be skeptical of nausea; take hives and any signs of anaphylaxis very seriously
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82
Q

What are penicillinases?

A

Beta-lactamases that are:

  • active against penicillins
  • inactive against cephalosporins
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83
Q

What are cephalosporinases?

A

Beta-lactamases that inactivate cephalosporins

-increasing in prevalence

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84
Q

Name the 1st generation cephalosporins?

A
  • Cefazolin
  • Cephalexin
  • cefadroxil
  • cephalothin
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85
Q

What is cefazolin?

A

1st generation cephalosporin

-parenteral

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86
Q

What is cephalexin?

A

1st generation cephalosporin

-oral

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87
Q

What is cefadroxil?

A

1st generation cephalosporin

-oral

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88
Q

What is cephalothin?

A

1st generation cephalosporin

-parenteral

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89
Q

What is the most commonly used class of antibiotics in the hospital?

A

1st generation cephalosporins

-used immediately prior to surgery to prevent surgical site infections

90
Q

Why are 1st generation cephalosporins ideal for prophylaxis of surgical site infections and treating skin and skin structure infections?

A
  • spectrum of activity
  • inexpensive cost
  • low incidence of adverse effects
91
Q

What organisms do 1st generation cephalosporins have GOOD activity against?

A
  • MSSA

- streptococci

92
Q

What organisms do 1st generation cephalosporins have MODERATE activity against?

A

-some enteric GNRs

93
Q

What organisms do 1st generation cephalosporins have POOR activity against?

A
  • enterococci
  • anaerobes
  • MRSA
  • Pseudomonas
94
Q

How do the adverse effects of 1st generation cephalosporins compare to other beta-lactams?

95
Q

Why are 1st generation cephalosporins a good alternative to antistaphylococcal penicillins?

A
  • cause less phlebitis

- infused less frequently

96
Q

How do 1st generation cephalosporins differ from antistaphylococcal penicillins?

A

May not cross the blood-brain barrier

-should not be used in CNS infections

97
Q

Which 1st generation cephalosporins are available orally?

A
  • cephalexin

- cefadroxil

98
Q

Which 1st generation cephalosporins are available parenterally?

A
  • cefazolin

- cephalothin

99
Q

What are 1st generation cephalosporins good for?

A
  • skin and skin structure infections
  • surgical prophylaxis
  • staphylococcal bloodstream infections
  • osteomyelitis
  • endocarditis (MSSA)
100
Q

How are 1st generation cephalosporins used for surgical prophylaxis in the hospital?

A
  • limit the duration of use
  • administering more than one dose should be the exception
  • giving more than 24 hours worth is rarely justified
  • extended use does not lower infection rates/can select for more resistant organisms later in the hospital stay
101
Q

Name the 2nd generation cephalosporins.

A
  • Cefuroxime
  • Cefoxitin
  • Cefotetan
  • Cefprozil
  • loracarbef
  • cefmetazole
  • cefonicid
  • cefamandole
  • cefaclor
102
Q

What is cefuroxime?

A

2nd generation cephalosporin

-IV/PO

103
Q

What is cefoxitin?

A

2nd generation cephalosporin

-IV

104
Q

What is cefotetan?

A

2nd generation cephalosporin

-IV

105
Q

What is Cefprozil?

A

2nd generation cephalosporin

-oral

106
Q

What is loracarbef?

A

2nd generation cephalosporin

-oral

107
Q

What is cefmetazole?

A

2nd generation cephalosporin

-IV

108
Q

What is cefonicid?

A

2nd generation cephalosporin

-IV

109
Q

What is cefamandole?

A

2nd generation cephalosporin

-IV

110
Q

What is cefaclor?

A

2nd generation cephalosporin

-oral

111
Q

How are 2nd generation cephalosporins different than 1st generation?

A
  • have better gram-negative activity
  • somewhat weaker gram-positive activity
  • more stable against gram-negative beta-lactamases
112
Q

What organisms are 2nd generation cephalosporins particularly active against?

A
  • H. influenzae

- N. gonorrhoeae

113
Q

What organisms do 2nd generation cephalosporins have GOOD activity against?

A
  • some enteric GNRs
  • Haemophilus
  • Neisseria
114
Q

What organisms do 2nd generation cephalosporins have MODERATE activity against?

A
  • streptococci
  • staphylococci
  • anaerobes (only cefmetazole, cefotetan, cefoxitin)
115
Q

What organisms do 2nd generation cephalosporins have POOR activity against?

A
  • enterococci
  • MRSA
  • Pseudomonas
116
Q

How do the adverse effects of 2nd generation cephalosporins compare to other beta-lactams?

117
Q

What cephalosporins have the MTT side chain?

A
  • cefmetazole
  • cefotetan
  • cefamandole
118
Q

What does MTT stand for?

A

N-methylthiotetrazole

119
Q

What side effects do cephalosporins with the MTT side chain have?

A
  • can inhibit vitamin K production (prolong bleeding)

- cause a disulfiram-like reaction when coadministered with ethanol

120
Q

What are cephamycins?

A

A sub-group of second generation cephalosporins that have anaerobic activity

  • have activity against many anaerobes in the GI tract
  • good intrinsic anaerobic activity (resistance is increasing in Bacteroides fragilis group infections)
  • cefmetazole
  • cefotetan
  • cefoxitin
121
Q

Which cephalosporins are often used for surgical prophylaxis in abdominal surgery?

A
  • cefoxitin

- cefotetan

122
Q

Which cephalosporin is a carbacephem?

A

Loracarbef

123
Q

Do 2nd generation cephalosporins cross the blood-brain barrier well?

A

No

-do not use them to treat CNS infections

124
Q

What are 2nd generation cephalosporins good for?

A
  • upper respiratory tract infections
  • community-acquired pneumonia
  • gonorrhea
  • surgical prophylaxis (cephamycins)
125
Q

How should cephamycins be used for surgical prophylaxis?

A

-limit duration of antibiotic exposure after surgery

If infection develops, use alternative agents:

  • beta-lactamase inhibitor combinations
  • another gram-negative agent + metronidazole
126
Q

Name the 3rd generation cephalosporins.

A
  • Ceftriaxone
  • Cefotaxime
  • Ceftazidime
  • Cefdinir
  • cefpodoxime
  • cefixime
  • ceftibuten
127
Q

What is ceftriaxone?

A

3rd generation cephalosporin

128
Q

What is cefotaxime?

A

3rd generation cephalosporin

129
Q

What is ceftazidime?

A

3rd generation cephalosporin

130
Q

What is cefdinir?

A

3rd generation cephalosporin

131
Q

What is cefpodoxime?

A

3rd generation cephalosporin

132
Q

What is cefixime?

A

3rd generation cephalosporin

133
Q

What is ceftibuten?

A

3rd generation cephalosporin

134
Q

How do 3rd generation cephalosporins compare to previous generations?

A
  • greater gram-negative activity
  • most have good streptococcal activity (generally lesser staphylococcal activity)
  • considered broad-spectrum agents
135
Q

What organisms do 3rd generation cephalosporins have GOOD activity against?

A
  • streptococci (except ceftazidime: poor)
  • enteric GNRs
  • Pseudomonas (ceftazidime)
136
Q

What organisms do 3rd generation cephalosporins have MODERATE activity against?

A

-MSSA (except ceftazidime: poor)

137
Q

What organisms do 3rd generation cephalosporins have POOR activity against?

A
  • enterococci
  • anaerobes
  • MRSA
  • Pseudomonas (except ceftazidime)
138
Q

How do the adverse effects of 3rd generation cephalosporins compare to other beta-lactams?

139
Q

What class of antibiotics has been shown to be one of the classes with the strongest association with Clostridium difficile-associated diarrhea?

A

3rd generation cephalosporins

140
Q

Which 3rd generation cephalosporin has the MTT side chain?

A

Cefpodoxime

141
Q

How is ceftazidime the exception among 3rd generation cephalosporins?

A
  • antipseudomonal

- lacks clinically useful activity against gram-positive organisms

142
Q

Which 3rd generation cephalosporins cross the blood-brain barrier effectively to treat CNS infections?

A
  • ceftriaxone
  • cefotaxime
  • ceftazidime

Ceftazidime is a poor choice for community-acquired meningitis (in which S. pneumoniae predominates)

143
Q

Which generation of cephalosporins is notorious for inducing resistance among GNRs?

A

3rd generation cephalosporins

-can be useful in nosocomial infections but too much broad spectrum utilization can result in harder to treat organisms

144
Q

What cephalosporin is a drug of choice for gonorrhea?

A

One time dose of ceftriaxone IM

  • 125mg (old dose)
  • 250mg (current dose) due to increasing resistance
145
Q

What drug should be added to a patient being treated for gonnorhea?

A

Azithromycin

  • adds empiric therapy for chlamydida
  • may reduce emergence of ceftriaxone resistance
147
Q

Does ceftriaxone need to be adjusted for renal dysfunction?

A

No

-however, does effectively treat UTIs

148
Q

Which 3rd generation cephalosporin is safer in neonates: ceftriaxone or cefotaxime?

A

Cefotaxime

149
Q

Why is ceftriaxone use in neonates problematic?

A
  • interacts with calcium-containing medications to form crystals (can precipitate in the lungs and kidneys; has led to fatalities)
  • can lead to biliary sludging (with resultant hyperbilirubinemia)
150
Q

How is ceftriaxone dosed for MSSA infections?

A

2-4 grams per day (particularly invasive infections)

-less activity against this organism means higher doses are recommended

151
Q

What are 3rd generation cephalosporins good for?

A
  • lower respiratory tract infections
  • pyelonephritis
  • nosocomial infections and febrile neutropenia (ceftazidime)
  • Lyme disease (ceftriaxone)
  • meningitis
  • gonorrhea
  • skin and skin structure infections
152
Q

How is ceftriaxone dosed for most infections?

A

Once daily

-except meningitis (2g IV q12h); also use vancomycin and ampicillin (if indicated)

153
Q

What is the only 4th generation cephalosporin?

154
Q

What is the broadest spectrum cephalosporin?

A

Cefepime

-has activity against gram positive and gram negative organisms (including Pseudomonas)

155
Q

What organisms does cefepime have GOOD activity against?

A
  • MSSA
  • streptococci
  • Pseudomonas
  • enteric GNRs
156
Q

What organisms does cefepime have MODERATE activity against?

A

-Acinetobacter

157
Q

What organisms does cefepime have POOR activity against?

A
  • enterococci
  • anaerobes
  • MRSA
158
Q

How do the adverse effects of cefepime compare to other beta-lactams?

A

Generally similar

-cefepime may be associated with more neurotoxicity than other agents

159
Q

How should cefepime be used empirically?

A

It is a broad spectrum agent

  • good empiric choice for many nosocomial infections
  • overkill for most community-acquired infections
  • de-escalate therapy whenever possible when treating empirically with cefepime
160
Q

Why is cefepime a better choice than ceftazidime for monotherapy of febrile neutropenia?

A
  • better gram positive activity
  • may induce less resistance in GNRs than 3rd generation cephalosporins
  • still not a good drug to overuse
161
Q

Why did cefepime previously have a bad reputation?

A

A meta-analysis showed increased mortality with its use compared with other drugs

-more thorough FDA analysis exonerated cefepime

162
Q

How does neurotoxicity occur with cefepime?

A

Can occur at any dose (dose adjustment with renal dysfunction is important)

-may manifest as nonconvulsive status epilepticus

163
Q

What is cefepime good for?

A
  • febrile neutropenia
  • nosocomial pneumonia
  • postneurosurgical meningitis
  • other nosocomial infections
164
Q

What types of infections is cefepime primarily used for?

A

Nosocomial infections

-indicated for UTIs and lower respiratory tract infections (but is overkill for most community acquired sources of these infections)

165
Q

How is ceftriaxone eliminated?

A

Dual modes of elimination:

  • renal
  • biliary excretion
166
Q

What is the only anti-MRSA cephalosporin currently on the market?

A

Ceftaroline

167
Q

What anti-MRSA cephalosporin was removed from the market?

A

Ceftobiprole

168
Q

What organism (besides MRSA) does ceftaroline have activity against that no other cephalosporin has?

A

Modest activity against E. faecalis (not E. faecium)

169
Q

How does the gram negative potency of ceftaroline compare to previous cephalosporins?

A

Similar to that of ceftriaxone

-lost some of the gram negative potency of cefepime

170
Q

Which characteristic of ceftaroline is responsible for its anti-MRSA activity?

A
  • can bind to penicillin-binding protein 2a (a type that is expressed by MRSA)
  • its structure has been engineered to bind to the penicillin-binding protein 2a of MRSA that has low affinity for other beta-lactams
171
Q

What organisms does ceftaroline have GOOD activity against?

A
  • MSSA
  • MRSA
  • streptococci
  • enteric GNRs
172
Q

What organisms does ceftaroline have MODERATE activity against?

A

-E. faecalis

173
Q

What organisms does ceftaroline have POOR activity against?

A
  • P. aeruginosa
  • E. faecium
  • Acinetobacter
  • anaerobes
174
Q

How do the adverse effects of ceftaroline compare to other beta-lactams?

175
Q

What are the initial indications for ceftaroline?

A

“Low hanging fruit” (which is typical for new antimicrobials coming to the market:

  • skin and skin structure infections
  • community acquired pneumonia

Many great agents are already available for these infections already

-challenge will be to determine its role in hospital acquired pneumonia and other severe diseases caused by drug resistant pathogens

176
Q

How did ceftaroline do against ceftriaxone in community acquired pneumonia?

A

Outperformed ceftriaxone in two of three studies

177
Q

What infections has ceftaroline been described to successfully treat in case series and retrospective studies?

A
  • bloodstream infections
  • endocarditis
  • meningitis
  • osteomyelitis
  • hospital-acquired pneumonia
178
Q

What is ceftaroline good for?

A

Approved (in the US) for treatment of:

  • complicated skin and soft tissue infections
  • community acquired pneumonia

Less rigorous data for other uses

179
Q

In which three key organisms is carbapenem resistance mostly seen?

A
  • Klebsiella pneumoniae
  • P. aeruginosa
  • A. baumannii
180
Q

What is avibactam?

A

New type of beta-lactamase inhibitor

MOA is different from other beta-lactamase inhibitors

-does not resemble a beta-lactam, but also binds beta-lactamases and renders them inert

181
Q

What beta-lactamases does avibactam work against?

A
  • K. pneumoniae

- P. aeruginosa

182
Q

What cephalosporin is avibactam combined with?

A

Ceftazidime

183
Q

What is ceftolozane?

A

3rd generation cephalosporin

-evades many resistance mechanisms of P. aeruginosa

184
Q

What cephalosporin is tazobactam combined with?

A

Ceftolozane

Tazobactam is a beta-lactamase inhibitor that structurally resembles beta-lactams and binds to many beta-lactamases (rendering them unable to inactivate the co-administered beta-lactam)

185
Q

What organisms do cephalosporin/beta-lactamase inhibitor combinations have GOOD activity against?

A
  • Pseudomonas

- enteric GNRs (ceftazidime/avibactam > ceftolozane/tazobactam)

186
Q

What organisms do cephalosporin/beta-lactamase inhibitor combinations have MODERATE activity against?

A

-some streptococci (ceftolozane/tazobactam)

187
Q

What organisms do cephalosporin/beta-lactamase inhibitor combinations have POOR activity against?

A
  • most anaerobes
  • MRSA
  • MSSA
  • Acinetobacter
188
Q

What resistant organism do cephalosporin/beta-lactamase inhibitor combinations NOT have good activity against?

A

Acinetobacter

189
Q

What resistant organism DO cephalosporin/beta-lactamase inhibitor combinations have good activity against?

A

Most multidrug-resistant Pseudomonas

-possible to see isolates of Pseudomonas that are resistant to one of these drugs and susceptible to the other

190
Q

Which cephalosporin/beta-lactamase inhibitor combination is active against carbapenem-resistant Klebsiella and other enteric GNRs?

A

Ceftazidime/avibactam

191
Q

How does ceftolozane evade Pseudomonas resistance?

A

It is minimally affected by many Pseudomonas resistance mechanisms (including its beta-lactamase)

-tazobactam adds little for this organism

192
Q

How does ceftazidime evade Pseudomonas resistance?

A

Relies on avibactam to inactivate Pseudomonas beta-lactamases

193
Q

Are cephalosporin/beta-lactamase inhibitor combinations effective against gut anaerobes?

A

No (due to substantial resistance)

-add metronidazole if anaerobic involvement suspected

This is unlike penicillin/beta-lactamase inhibitor combination

194
Q

What are BOTH cephalosporin/beta-lactamase inhibitor combinations good for?

A
  • multidrug-resistant Pseudomonas infections
  • mixed aerobic/anaerobic infections
  • intra-abdominal infections
  • infections caused by ESBL-producing organisms
195
Q

What is ceftazidime/avibactam good for?

A

-carbapenem-resistant Enterobacteriaceae infections

196
Q

Name the carbapenems.

A
  • Imipenem/cilastatin
  • Meropenem
  • Ertapenem
  • doripenem
197
Q

What are carbapenems?

A

Broadest spectrum antibacterial drugs

-possess a beta-lactam ring and share the same MOA of beta-lactams (but are structurally unique and different from penicillins/cephalosporins)

Ertapenem has important differences in its spectrum (it is the EXCEPTION)

198
Q

What organisms do carbapenems have GOOD activity against?

A
  • MSSA
  • streptococci
  • anaerobes
  • enteric GNRs
  • Pseudomonas (not ertapenem)
  • Acinetobacter (not ertapenem)
  • ESBL-producing GNRs
199
Q

What organisms do carbapenems have MODERATE activity against?

A

-enterococci (not ertapenem)

200
Q

What organisms do carbapenems have POOR activity against?

A
  • MRSA

- penicillin-resistant streptococci

201
Q

How do the adverse effects of carbapenems compare to other beta-lactams?

A

Similar

Imipenem has a higher propensity to induce seizures

  • calculate appropriate doses for patients with renal dysfunction
  • avoid use in meningitis (can cross the blood-brain barrier more easily)
202
Q

Why is cilastatin always coadministered with imipenem?

A

Imipenem is metabolized in the kidney to a nephrotoxic product

-cilastatin blocks the renal dehydropeptidase that catalysts this reaction (prevents this metabolism from occurring

203
Q

What types of infections are carbapenems good for?

A

Are very broad-spectrum agents

  • should not be used empirically for most community-acquired infections
  • good choices for many types of nosocomial infections (particularly if patients received other classes of antibiotics during their hospital stay)
204
Q

What is a disadvantage of ertapenem?

A

Poor choice for nosocomial infections

-particularly nosocomial pneumonia (where Pseudomonas and Acinetobacter are important pathogens)

205
Q

What is an advantage of ertapenem?

A

Administered only once a day

-may be a better choice for home-infusion therapy for susceptible infections

206
Q

Describe carbapenem cross-allergenicity with penicillin.

A
  • one study showed incidence of an allergic reaction in patients with a history of penicillin allergy to be as high as 47% with a proven penicillin allergy
  • recent better performed studies in patients with anaphylaxis to penicillin show this number to be closer to 1%
  • patients with a history of allergy to any drug are more likely to react to another one even if they are not related
207
Q

Do carbapenemases exist?

A

Yes; render carbapenems inert

-most common in the northeast US; very common in other parts of the world

208
Q

What are ALL carbapenems good for?

A
  • mixed aerobic/anaerobic infections
  • infections caused by ESBL producing organisms
  • intra-abdominal infections
209
Q

What are carbapenems EXCEPT ertapenem good for?

A
  • nosocomial pneumonia
  • febrile neutropenia
  • other nosocomial infections
210
Q

What is the only monobactam?

211
Q

Describe the structure of aztreonam.

A

Contains only the four-membered ring of the basic beta-lactam structure

212
Q

Aztreonam is safe to administer to patients with allergies to other beta lactamases, except?

A

Specific allergy to ceftazidime (shares an identical side chain with aztreonam)

-ceftolozane also shares this side chain

213
Q

What beta-lactam does aztreonam share the same spectrum of activity with?

A

Ceftazidime

214
Q

What organisms does aztreonam have GOOD activity against?

A
  • Pseudomonas

- most GNRs

215
Q

What organisms does aztreonam have MODERATE activity against?

A

-Acinetobacter

216
Q

What organisms does aztreonam have POOR activity against?

A
  • gram positive organisms

- anaerobes

217
Q

How do the adverse effects of aztreonam compare to other beta-lactams?

A

Similar

-low incidence of hypersensitivity

218
Q

What class of drugs is aztreonam often confused with?

A

Aminoglycosides

  • is chemically unrelated and does not share their toxicities
  • shares MOA and pharmacodynamic profile with other beta-lactams
219
Q

When can aztreonam be administered via inhalation?

A

To patients with cystic fibrosis to prevent exacerbations of infection

220
Q

Should aztreonam be combined with other beta-lactams?

A

Not warranted against the same organism

-add a non-beta-lactam to empiric regimen for serious nosocomial infections

221
Q

What is aztreonam good for?

A

Gram negative infections

-including Pseudomonas (particularly in patients with a history of beta-lactam allergy)

Antibiotics (63 decks)

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