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Cephalosporins Flashcards

1
Q

Cephalosporin nucleus

A

beta-lactam ring linked to a dihydrothiazine ring

4 ring then 6 ring with a sulfur in the 6 ring

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2
Q

C3 alterations

A

change pharmacokinetics

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3
Q

C7 alterations

A

change spectrum of activity

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4
Q

Cephalosporins MOA:

A

interfere with transpeptidase PBP which disrupts the cross linking which also weakens cell wall and initiates lytic cycle

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5
Q

Cephalosporins are bactericidal/bacteriostatic

A

bactericidal

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6
Q

Bactericidal activity of cephalosporins depends on

A

duration of time that free drug levels exceed MIC

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7
Q

Cephalosporins have the ____ % time> MIC requirement

A

longest; needs to be 60-70 %

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8
Q

General rule for cephalosporin activity in terms of this order and gram + and gram -

cefazolin 1st
cefuroxime 2nd
ceftriaxone 3rd
cefepime 4th
ceftaroline anti MRSA
A

gram + : activity decreases as you go down but increases for ceftaroline so it has 2 triangles touching each other at the tips where cefepime is

gram - : increase as you go down the list and tapers off at ceftaroline, it looks like a stiletto shaped nail

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9
Q

First generation cephalosporins include:

A

cefazolin, cephalexin, cefadroxil

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10
Q

Cefazolin oral absorption:

A

poor IV only

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11
Q

Cefazolin 1/2 life

A

short but the longest in terms of 1st gen cephalosporins

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12
Q

Cefazolin eliminination

A

renal

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13
Q

Cephalexin oral absorption

A

high

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14
Q

Cephalexin 1/2 life

A

short

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15
Q

Cephalexin elimination

A

renal

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16
Q

Cefadroxil oral absorption

A

high

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17
Q

Cefadroxil 1/2 life

A

short

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18
Q

Cefadroxil elimination

A

renal

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19
Q

1st Generation tissue penetration

A

skin
bone/joint
urine
lung-variable

CSF is POOR due to active efflux from BBB

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20
Q

1st Generation spectrum coverage

A

dark purple: streptococcus, viridans, MSSA/MSSE
dark red: E. coli, klebsiella, p. mirabilis
light red: Neisseria
anaerobes: +/- (just oral)

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21
Q

Important: Cephalosporins do not cover which organism?

A

enterococcus

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22
Q

1st Generation indications

A 
skin/skin structure infections (MSSA, s. pyogenes/s. agalactiae)
UTI (E. coli)
surgical prophylaxis (cefazolin)

definitive therapy for MSSA

  • endocarditis
  • osteomyelitis
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23
Q

Second generation cephalosporins include:

A

cefprozil, cefaclor, cefuroxime, cefotetan, cefoxitin

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24
Q

Second generation cephalosporins used for respiratory infections:

A

cefprozil, cefaclor, cefuroxime

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25
Q

Cefprozil oral absorption

A

high

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26
Q

Cefprozil 1/2 life

A

short

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27
Q

Cefprozil elimination

A

35-45 %

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28
Q

Cefaclor oral absorption

A

high

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29
Q

Cefaclor 1/2 life

A

short

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30
Q

Cefaclor elimination

A

70% renal

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31
Q

Cefuroxime oral absorption

A

52% (axetil)

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32
Q

Cefuroxime 1/2 life

A

short

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33
Q

Cefuroxime elimination

A

90% renal

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34
Q

Second generation cephalosporins that are cephamycins

A

cefotetan and cefoxitin

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35
Q

Cefotetan oral absorption

A

poor IV only

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36
Q

Cefotetan 1/2 life

A

longer 3.5 hrs

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37
Q

Cefotetan elimination

A

75% renal

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38
Q

Cefoxitin oral absorption

A

poor IV only

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39
Q

Cefoxitin 1/2 life

A

short

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40
Q

Cefoxitin elimination

A

80% renal

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41
Q

2nd Generation tissue penetration

A 
skin
bone/joint
urine
respiratory
intra-ab

CSF is variable- cefuroxime IV penetrates but is clinicaly inferior to ceftriaxone/cefotaxime for meningitis

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42
Q

2nd Generation spectrum coverage for respiratory

A

dark purple: streptococcus, s. pneumoniae, viridans, MSSA/MSSE
dark red: h. influenzae, m. catarrhalis, E. coli, klebsiella, p. mirabilis
light red: Neisseria, morganella
anaerobes: +/- (just oral)

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43
Q

2nd Generation spectrum coverage for cephamycins

A

dark purple: streptococcus, s. pneumoniae, viridans, MSSA/MSSE
dark red: h. influenzae, m. catarrhalis, E. coli, klebsiella, p. mirabilis
light red: Neisseria, morganella
anaerobes: + active against most but some resistance found in b. fragilis

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44
Q

2nd Generation cephalosporin indications

A

upper and lower respiratory infections
otitis media
UTI

cephamycins:
intra-ab infections
mycobacterial infections (cefoxitin)
surgical prophylaxis

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45
Q

Third Generation cephalosporins include

A

cefixime, cefdinir, cefpodoxime, ceftriaxone, cefotaxime

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46
Q

Cefixime oral absorption

A

50% so fair

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47
Q

Cefixime 1/2 life

A

longer 3-4 hours

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48
Q

Cefixime elimination

A

35-45% renal

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49
Q

Cefdinir oral absorption

A

21% poor

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50
Q

Cefdinir 1/2 life

A

short

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51
Q

Cefdinir elimination

A

20% renal

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52
Q

Cefpodoxime oral absorption

A

50% so fair

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53
Q

Cefpodoxime 1/2 life

54
Q

Cefpodoxime elimination

55
Q

Ceftriaxone oral absorption

A

none IV only

56
Q

Ceftriaxone 1/2 life

A

long 8.5 hours

57
Q

Ceftriaxone elimination

A

30-65% renal

58
Q

Cefotaxime oral absorption

A

none IV only

59
Q

Cefotaxime 1/2 life

60
Q

Cefotaxime elimination

61
Q

3rd Generation cephalosporin tissue penetration

A 
skin
bone/joint
urine
respiratory
intra-ab
CNS
62
Q

3rd Generation cephalosporin spectrum coverage

A

dark purple: streptococcus, s. pneumoniae, viridans
light purple: MSSA/MSSE
dark red: Neisseria, h. influenzae, m. catarrhalis, E. coli, klebsiella, p. mirabilis, morganella
light red: eneterbacter, citrobacter, serratia (all 3 of these induce AmpC and led to ESBL)
anaerobes: +/- (oral only)
Misc: no activity against ESBL, poor activity against AmpC

63
Q

3rd Generation cephalosporin indications

A 
upper and lower respiratory infections
otitis media
UTI
CNS
intra-ab infections
skin and soft tissue infections
bone and joint infections
64
Q

Common dosing for meningitis using ceftriaxone

A

1-2 gm IV q12h

65
Q

Common resistance for cephalosporins

A

AmpC beta-lactamases

  • encoded on chromosomes of enterobacteriaceae and P. aeruginosa
  • inducible by enterobacter
  • resistance observed to all 3 generations

ESBL

  • e.coli and klebsiella
  • resistance observed to all 3 generations

Altered target binding in gram positive cocci

66
Q

Adverse events for cephalosporins

A 
CNS with 3rd gen
GI
hyperbilirubinemia
renal
skin
anaphylaxis
cross reactivity with PCN allergy
hematologic
disulfiram reaction
67
Q

Adverse events to remember for cephalosporins

A
  • CNS with 3rd generation
  • cross reactivity in patients with PCN allergy, DO NOT USE in patients who get anaphylaxis to PCN
  • Disulfiram reaction with alcohol (cefotetan mostly)
68
Q

Drug interactions in cephalosporins

A
  • probenecid (block tubular secretion, so increases serum concentration/1/2 life)
  • cetriaxone with calcium (forms insoluble precipitate) and contraindicated in neonates 28 day or younger
  • iron supplement should be separated from cefdinir by 2 hours before or after (decreased absorption)
69
Q

All cephalosporins (1,2,3 gen) do not cover

A

MRSA, enterococcus, P. aeruginosa, and acinetobacter

70
Q

Ceftazidime is an

A

anti-pseudomonal cephalosporin

71
Q

Ceftazidime structure differences help to

A

increase activity against gram - bacilli, increase stability against some beta-lactamase and increases pseudomonas activity, zwitterionic properties

72
Q

Ceftazidime is generally unstable against

A

ESBL, AmpC, carbapenemases

73
Q

Cefepime is an

A

anti-pseudomonal cephalosporin

74
Q

Cefepime structure causes it to be

A

zwitterion at neutral pH

75
Q

Ceftazidime is a ____ generation cephalosporin

76
Q

Cefepime is a _____ generation cephalosporin

77
Q

Ceftazidime oral absorption

A

poor IV only

78
Q

Ceftazidime 1/2 life

A

short 2 hours

79
Q

Ceftazidime elimination

80
Q

Cefepime oral absorption

A

poor IV only

81
Q

Cefepime 1/2 life

A

short 2.2 hours

82
Q

Cefepime elimination

83
Q

Ceftazidime/Cefepime tissue distribution

A 
skin
bone/joint
urine
lung
CNS with inflammation
intra-ab
84
Q

Ceftazidime spectrum coverage

A

light purple: streptococcus, s. pneumoniae
dark red: h. influenzae, m. catarrhalis, E. coli, klebsiella, p. mirabilis, morganella, p. aeruginosa
light red: Neisseria, enterobacter, citrobacter, serratia
anaerobes: +/- (oral only)
Misc: activity against achromobacter and s. maltophilia, unstable against ESBL and AmpC

85
Q

Cefepime spectrum coverage

A

dark purple: streptococcus, s. pneumoniae, MSSA/MSSE
light purple: viridans
dark red: Neisseria, h. infleunzae, m. catarrhalis, e. coli, klebsiella, p. mirabilis, Morganella, enterobacter, citrobacter, serratia, p. aeruginosa
light red: acinetobacter
anaerobes: +/- (oral)
Misc: stable against AmpC, poor activity against S. maltophilia and achromobacter

86
Q

Ceftazidime/Cefepime indications

A

healthcare associated infections like pneumonia, CNS, skin and skin structure, intra-ab, UTI

Cefepime is often preferred to improve gram + activity and it has better activity against MSSA

87
Q

Cephalosporin/inhibitor agents

A

ceftazidime/avibactam, ceftolozane/tazobactam

88
Q

Avibactam is a ____ inhibitor

A

non suicidal; able to be recycled

89
Q

Avibactam is a

A

non-beta-lactam beta-lactamase inhibitor and improves binding affinity

90
Q

Avibactam inhibits

A

ESBL, AmpC, and some OXA-type

91
Q

Ceftolozane/tazobactam structure

A

C7 side chain allows for enhanced gram - coverage

C3 side chain improves p. aeruginosa activity

92
Q

Tazobactam provides some stability against

93
Q

Ceftazidime/avibactam oral absorption

A

poor IV only

94
Q

Ceftazidime/avibactam 1/2 life

A

2/2.7 so short

95
Q

Ceftazidime/avibactam elimination

96
Q

Ceftolozane/tazobactam oral absorption

A

poor IV only

97
Q

Ceftolozane/tazobactam 1/2 life

A

2.8/1 so short

98
Q

Ceftolozane/tazobactam elimination

99
Q

Ceftazidime/avibactam and Ceftolozane/tazobactam tissue penetration

A 
skin
bone/joint
urine
respiratory
intra-ab
100
Q

Ceftazidime/avibactam spectrum coverage

A

dark purple: MSSA
light purple: streptococcus, s. pneumoniae
dark red: h. influenzae, m. catarrhalis, E. coli, klebsiella, p. mirabilis, morganella, enterobacter, citrobacter, serratia, P. aeruginosa
light red: Neisseria
anaerobes: +/- (oral)
Misc: ceftazidime has poor activity against b. fragilis, has activity against KPC, ESBL, AmpC

101
Q

Ceftolozane/tazobactam spectrum coverage

A

dark purple: streptococcus
light purple: s. pneumoniae, viridans
dark red: h. influenzae, m. catarrhalis, E. coli, klebsiella, p. mirabilis, morganella, citrobacter, serratia, p. aeruginosa
light red: Neisseria, enterobacter, acinetobacter
anaerobes: +/- (oral)
Misc: cetfolozane has poor activity against b. fragilis, is active against carbapenem resistant pseudomonas

102
Q

Ceftazidime/avibactam indications

A
  • predominant role will be KPC-producing organisms

- has activity against ESBL and AmpC producing organisms but not better than carbapenems

103
Q

Ceftolozane/tazobactam indications

A

P. aeruginosa, especially carbapenem resistant isolates

104
Q

Cefiderocol is a ____ cephalosporin

A

siderophore

105
Q

Cefiderocol has a novel MOA

A

binds to free extracellular ferric iron and actively transports itself across the outer cell membrane of bacteria into periplasmic space using siderophore iron uptake mechanism (Trojan horse)

106
Q

Cefiderocol is bactericidal/bacteristatic

A

bactericidal

107
Q

Cefiderocol is bactericidal through

A

inhibiting cell wall synthesis through binding to PBP

108
Q

Cefiderocol oral absorption

A

poor IV only

109
Q

Cefiderocol 1/2 life

A

2-3 hours so medium/short

110
Q

Cefiderocol elimination

111
Q

Cefiderocol spectrum coverage

A

ONLY GRAM -
dark red: h. influenzae, m. catarrhalis, E. coli, klebsiella, p. mirabilis, morganella, enterobacter, citrobacter, serratia, p. aeruginosa, acinetobacter
light red: Neisseria
Misc: active against carbapenem- resistant pseudomonas and enterobacteriaceae and s. maltophilia
active against ESBL, AmpC, KPC, OXA-type, MBL carbapenemases

112
Q

Cefiderocol indications

A

multi-drug-resistant gram - infections like UTI, pneumonia, bacteremia

113
Q

Anti-staphylococcal cephalosporin

A

ceftaroline

114
Q

Ceftaroline is a

115
Q

phosphono group was added to Ceftaroline to

A

improve solubility

116
Q

Ceftaroline has enhanced activity against

A

PBP2a and MRSA

117
Q

Ceftaroline’s structure allows it to be

A

zwitterion

118
Q

Ceftaroline oral absorption

A

poor IV only

119
Q

Ceftaroline 1/2 life

A

2-3 so medium/short

120
Q

Ceftaroline elimination

A

40-70% renal

121
Q

Ceftaroline tissue penetration

A 
skin
bone/joint
urine
respiratory
intra-ab
CNS (animal models)
122
Q

Ceftaroline spectrum coverage

A

Same as ceftiaxone + MRSA
dark purple: streptococcus, s. pneumoniae, viridans, MSSA/MSSE, MRSA/MRSE
dark red: Neisseria, h. influenzae, m. catarrhalis, E. coli, klebsiella, p. mirabilis, morganella
light red: enterobacter, citrobacter, serratia
anaerobes: +/- (oral)
Misc: no activity against ESBL, poor activity against Ampc

123
Q

Ceftaroline does not cover

A

enterococcus and p. aeruginosa and acinetobacter

124
Q

Ceftaroline indications

A

pneumonia, bacteremia, skin and skin structure

125
Q

Ceftaroline adverse events

A 
CNS
GI
renal
skin
anaphylaxis
hematologic
126
Q

Which drugs improved activity against nosocomial pathogens including p. aeruginosa?

A

cefepime and ceftazidime and ceftolozone/tazobactam

127
Q

Cefepime has improved

A

gram + coverage

128
Q

Which drug has improved activity against carbapenem resistant pseudomonas, enterobacteriacae, and acinetobacter?

A

cefiderocol

129
Q

Cefiderocol does not have reliable ____ coverage

A

gram + and anaerobic

130
Q

Valuable drug for MRSA management

A

Ceftaroline

PC2 (18 decks)

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