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Neonatal Pharmacology - Fall 2021 > Antimicrobials > Flashcards

Antimicrobials Flashcards

1
Q

What are the natural penicillins?

A

Penicillin G
Penicillin V
Penicillin G procaine
Penicillin G benzathine

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2
Q

Which natural penicillins should ONLY be given IM?

A

Penicillin G procaine
Penicillin G benzathine

Given IV could kill the patient.

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3
Q

What are the aminopenicillins?

A

Amoxicillin

Ampicillin

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4
Q

What are the penicillinase-resistant penicillins?

A 
Cloxacillin
Dicloxacillin
Oxacillin
Nafcillin
Methicillin
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5
Q

Which penicillin is an extended spectrum penicillin?

A

Piperacillin

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6
Q

What causes penicillin resistance?

A

Beta-lactamase, which binds to the beta-lactam forming an acyl enzyme intermediate which under goes rapid hydrolysis (destroying the drug).

Alteration of the penicillin binding proteins (what penicillin binds to and alters) accounts for resistance among pneumococci, some Haemophilus Flu, and some Neisseria.

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7
Q

Penicillin G:

Half-Life, Protein Binding, Route of Excretion

A

HL: 0.5-1.2 hours
PB: 55-65%
RE: Renal

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8
Q

Nafcillin:

Half-Life, Protein Binding, Route of Excretion

A

HL: 0.5 hour
PB: 87-90%
RE: Hepatic then renal

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9
Q

Ampicillin:

Half-Life, Protein Binding, Route of Excretion

A

HL: 1 hour
PB: 15-25%
RE: Renal

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10
Q

Amoxicillin:

Half-Life, Protein Binding, Route of Excretion

A

HL: 1 hour
PB: 17-20%
RE: Renal

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11
Q

Piperacillin:

Half-Life, Protein Binding, Route of Excretion

A

HL: 0.5-1.3 hours
PB: 22%
RE: Renal

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12
Q

Which categories of bugs are sensitive to penicillins?

A 
Gram + cocci
Gram + bacilli
Gram - bacteria
Anaerobic bacteria
Spirochetes
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13
Q

Penicillin V:

Half-Life, Protein Binding, Route of Excretion

A

HL: 1 hour
PB: 80%
RE: Renal

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14
Q 
Penicillin G: 
Dosing Recommendations (based on birthweight)
A

<1.2kg: 25,000-50,000U q12h

Less than one week old
1.2-2kg: 
25,000-50,000U q12h
>2kg: 
25,000-50,000 q8h
Over one week old
1.2-2kg:
25,000-50,000U q8h
>2kg:
25,000-50,000u q6h
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15
Q 
Ampicillin:
Dosing Recommendations (based on birthweight)
A

<1.2kg: 25-50mg/kg q12h

Less than one week old:
1.2-2kg:
25-50mg/kg q12h
>2kg:
25-50mg/kg q8h
Over one week old:
1.2-2kg:
25-50mg/kg q8h
>2kg:
25-50mg/kg q6h
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16
Q 
Nafcillin:
Dosing Recommendations (based on birthweight)
A

<1.2kg: 25mg/kg q12h

Less than one week old:
1.2-2kg:
25mg/kg q12h
>2kg:
25mg/kg q8h
Over one week old:
1.2-2kg:
25mg/kg q8h
1.2-2kg:
25-35mg/kg q6h
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17
Q

Aminopenicillin: Resistances

A

Anything with beta-lactamases

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18
Q

Aminopenicillin: Clearance

A

Kidneys

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19
Q

What is Zosyn a combination of?

A

Piperacillin (broad spectrum penicillin) and Tazobactam (beta-lactamase inhibitor)

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20
Q

Cephalosporins: Mechanism of Action

A

Interfere with synthesis of peptidoglycan in the bacterial cell wall

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21
Q

What does a cephalosporin generation tell you?

A

Its spectrum of microbiologic activity

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22
Q

What is the gram coverage progression of cephalosporins?

A

Gen 1 is mostly Gram +, but slowly adds more Gram - coverage as the generations progress.

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23
Q

Cephalosporin: Excretion

A

Kidneys (adjust dose with renal insufficiency)

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24
Q

Ceftazidime:

Half-life, Protein Binding, Route of Excretion

A

HL: 1.9h
PB: 20%
RE: Renal

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25
Q

Cefepime:

Half-life, Protein Binding, Route of Excretion

A

HL: 1.5-1.7h
PB: 19%
RE: Renal

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26
Q

Cefazolin:

Half-life, Protein Binding, Route of Excretion

A

HL: 1.4h
PB: 86%
RE: Renal

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27
Q 
Cefazolin:
Dosing Recommendations (based on birthweight)
A

<1.2kg:
20mg/kg/day q12h

Less than one week:
1.2-2kg
20mg/kg/day q12h
>2kg
20mg/kg/day q12h
Over one week:
1.2-2kg
20mg/kg/day q12h
>2kg
20mg/kg/day q8h
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28
Q 
Ceftazidime:
Dosing Recommendations (based on birthweight)
A

<1.2kg:
50mg/kg/day q12h

Less than one week:
1.2-2kg
50mg/kg/day q12h
>2kg
50mg/kg/day q8-12h
Over one week:
1.2-2kg
50mg/kg/day q8h
>2kg
50mg/kg/day q8h
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29
Q

Vancomycin:

Half-life, Protein Binding, Route of Excretion

A

HL: 3.5-10haxed
PB: 25-50%
RE: RENAL

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30
Q

Aminoglycosides:

Mechanism of Action

A

Binds to phospholipids and proteins on bacterial cell membrane, disturbing and inhibiting protein synthesis.

Once in the cytosol, interacts with mRNA translation and prevents protein synthesis (quality or quantity).

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31
Q

Aminoglycosides:

Four distinct antimicrobial aspects

A
  1. Concentration dependent killing
  2. Adaptive resistance
  3. Post antibiotic effect
  4. Syngerism with other antibiotics

These in combination constitute the rationale for extended-interval dosing

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32
Q

Ampicillin:

Gram Effectiveness

A

Positive

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33
Q

Vancomycin:

Gram Effectiveness

A

Positive

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34
Q

Gentamicin:

Gram Effectiveness

A

Negative

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35
Q

Penicillin:

Gram Effectiveness

A

Positive

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36
Q

Zosyn:

Gram Effectiveness

A

Gram negative (is broad spectrum)

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37
Q

Meropenem:

Gram Effectiveness

A

Gram negative (broad-spectrum)

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38
Q

Cefazolin:

Gram Effectiveness

A

Positive

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39
Q

What’s the trade name for cefazolin?

A

Ancef

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40
Q

Cefotaxime:

Gram Effectiveness

A

Negative

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41
Q

Cefepime:

Gram Effectiveness

A

Negative

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42
Q

Ampicillin:
Use Against which Bugs?
Which Bug is Resistant?

A

Streptococcus, LISTERIA, enterococcus (+ gent)

DO NOT USE FOR STAPH

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43
Q

Ampicillin:

Mechanism of Action

A

Interferes with bacterial cell wall synthesis by binding penicillin-binding proteins and causes cell wall beath by inhibiting peptidoglycan synthesis.

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44
Q

Ampicillin:

Toxicity

A

Diarrhea, feeding intolerance, rash

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45
Q

Ampicillin:

Does it cross the blood-brain barrier?

A

Yes

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46
Q

Cefazolin:

Use Against which Bug?

A

MSSA - used perioperatively for prophylaxis against staph

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47
Q

Cefazolin:

Which Generation?

A

First

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48
Q

Cefazolin:

Mechanism of Action

A

Interferes with bacterial cell wall synthesis by binding penicillin-binding proteins and causes cell wall beath by inhibiting peptidoglycan synthesis.

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49
Q

Cefazolin:

Toxicity

A

Phlebitis (rare)

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50
Q

Cefazolin:

Which procedure do we use it most for?

A

PDA ligation

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51
Q

Nafcillin:

Gram Effectiveness

A

Positve

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52
Q

Nafcillin:

Use Against which Bugs?

A

Staph, strep, staph aureus MSSA

Nafcillin is better at killing MSSA than vancomycin, but it’s rare the germ has a sensitivity to Nafcillin, so Vanc is used more frequently.

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53
Q

Nafcillin:

Mechanism of Action

A

Interferes with bacterial cell wall synthesis by binding penicillin-binding proteins and causes cell wall beath by inhibiting peptidoglycan synthesis.

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54
Q

Nafcillin:

Toxicity

A

Thrombophlebitis (really nasty on the vessels), leukopenia

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55
Q

Nafcillin:

Does it cross the blood-brain barrier?

A

Yes, especially with staph in the CSF

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56
Q

Nafcillin:

Metabolism

A

Liver

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57
Q

Penicillin G:

Use Against which Bugs?

A

Untreated/inadequately treated maternal SYPHILIS, gonococcal infection, strep

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58
Q

Penicillin G:

Mechanism of Action

A

Interferes with bacterial cell wall synthesis by binding penicillin-binding proteins and causes cell wall beath by inhibiting peptidoglycan synthesis.

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59
Q

Penicillin G:

Toxicity

A

Very rare CNS toxicity, adjust for renal dysfunction

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60
Q

Vancomycin:

Use Against which Bugs?

A

MRSA, Mec A gene present, coag negative staph

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61
Q

Vancomycin:

Mechanism of Action

A

Binds D-alanyl-D-alanine blocking peptidoglycan synthesis (inhibits cell wall synthesis)

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62
Q

Vancomycin:

Toxicity

A

Redman syndrome, flushing, hypotension, ototoxicity, nephrotoxicity

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63
Q

Vancomycin:

Does it cross the blood-brain barrier?

A

No

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64
Q

Vancomycin:

What is Vanc MIC >=2

A

Add another abx to help

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65
Q

Vancomycin:

Levels

A

Peak: 35-45 mcg/mL (2 hours from start)
Trough: 15-20 mcg/mL

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66
Q

Vancomycin:

Where is the killing power?

A

Trough

67
Q

Rifampin:

Use Against which Bugs?

A

Staph - in combination with other antibiotics because bugs gain rapid resistance if used by itself.

68
Q

Rifampin:

Mechanism of Action

A

Inhibits bacterial RNA synthesis

69
Q

Rifampin:

Toxicity

A

Blood dyscrasia (leukopenia, thrombocytopenia), cholestasis (jaundice, increased LFT, red-orange body fluid)

70
Q

Rifampin:

Clearance

A

Hepatically cleared, amplifies cyp-450 (interacts with many medications)

71
Q

Rifampin:

Does it cross the blood-brain barrier?

A

Yes

72
Q

Tobramycin:

Use Against which Bugs?

A

E. Coli, Enterobacter, pseudomonas, H-flu, Klebsiella, Serratia, other gram - in synergy with amp for CBS and enterococcus.

73
Q

Tobramycin:

Gram Effectiveness

A

Negative

74
Q

Tobramycin:

Mechanism of Action

A

Binds 30S ribosomal subunits inhibiting protein synthesis, block further translation, causes premature termination and incorporation of incorrect amino acids

75
Q

Tobramycin:

Toxicity

A

OTOTOXICITY, nephrotoxicity

76
Q

Tobramycin:

Does it cross the blood-brain barrier?

A

Nope

77
Q

Gentamicin:

Where is the killing power?

A

Peak (concentration-dependent killing - the higher we go, the higher the killing power)

78
Q

Gentamicin:

Why do we care about the trough?

A

Renal dysfunction leading to poor clearance: nephrotoxicity and ototoxicity

79
Q

Gentamicin:

When to obtain levels with extended dosing?

A

24 hours after the second dose: based on the volume of distribution and half-life for the postnatal age and gestational age of the infant

80
Q

Gentamicin:

Issues with Extended Dosing

A

Large Vd may not yield a high peak

Change to cefotaxime if there are issues with Vd and half-life

If trough <0.3mcg/mL then measure a peak and do first-order kinetics - not sure how long it’s been that low

81
Q

Cefotaxime:

Use Against which Bugs?

A

Non-Pseudomonal gram-negative rods: E Coli, H flu, Klebsiella

82
Q

Cefotaxime:

Mechanism of Action

A

Interferes with bacterial cell wall synthesis by binding penicillin-binding proteins and causes cell wall death by inhibiting peptidoglycan synthesis.

83
Q

Cefotaxime:

Toxicity

A

Local phlebitis, diarrhea, pseudomembranous colitis, thrombocytopenia

84
Q

Cefotaxime:

Synergy with Ampicillin?

A

Nope

85
Q

Cefotaxime:

Does it cross the blood-brain barrier?

A

Yes

86
Q

Cefotaxime:

Large or narrow therapeutic window?

A

Large: can use for large volumes of distribution and crappy clearance

87
Q

Cefotaxime:

What infection does it increase the risk for?

A

Fungal infections

88
Q

Cefotaxime:

Which generation cephalosporin is it?

A

Third

89
Q

Ceftazidime:

Gram effectiveness

A

Negative

90
Q

Ceftazidime:

Use Against which Bugs?

A

PSEUDOMONAS, E. Coli, Enterobacter, H flu, Klebsiella, other gram-negative rods

91
Q

Ceftazidime:

Which generation cephalosporin is it?

A

Third

92
Q

Ceftazidime:

Mechanism of Action

A

Interferes with bacterial cell wall synthesis by binding penicillin-binding proteins and causes cell wall death by inhibiting peptidoglycan synthesis.

93
Q

Ceftazidime:

Toxicity

A

Interferes with bacterial cell wall synthesis by binding penicillin-binding proteins and causes cell wall death by inhibiting peptidoglycan synthesis.

94
Q

Ceftazidime:

Does it cross the blood-brain barrier?

A

Yes

95
Q

Cefepime:

Gram effectiveness

A

Negative

96
Q

Cefepime:

Use Against which Bugs?

A

P.S.E.U.D.O.M.O.N.A.S (use before ceftazidime), E coli, Enterobacter, Serratia, H flu, Klebsiella, other gram-negative rods

97
Q

Cefepime:

Mechanism of Action

A

Interferes with bacterial cell wall synthesis by binding penicillin-binding proteins and causes cell wall death by inhibiting peptidoglycan synthesis.

98
Q

Cefepime:

Toxicity

A

Local phlebitis, diarrhea, pseudomembranous colitis, thrombocytopenia

99
Q

Cefepime:

Does it cross the blood-brain barrier?

A

Yes

100
Q

Cefepime:

Which cephalosporin generation?

A

Fourth

101
Q

Cefepime:

Amp C-gene

A

Use in multi-resistance, Pseudomonas Meningitis, Pathogens known to exhibit Amp C gene.
Amp C gene- a chromosomal class C Beta lactamase
Enterobacter and Serratia exhibit Amp C
Pathogens with the Amp C gene can report susceptibilities to Cephalosporins but rapidly grow resistance while being treated. Cefepime is a fourth-generation cephalosporin that has more resistance to Amp C

102
Q

Carbapenems:

Broad or Narrow Spectrum?

A

Broad

103
Q

Meropenem:

Use Against which Bugs?

A

Multidrug resistant gram negative infections: pseudomonas, Enterobacter

104
Q

Meropenem:

Mechanism of Action

A

Inhibits cell wall synthesis by binding PCN-binding proteins

105
Q

Meropenem:

Toxicity

A

Pseudomembranous colitis, seizures, diarrhea, false positive Coombs test, HYPOKLAMIEA

106
Q

Meropenem:

Does it cross the blood-brain barrier?

A

Yes

107
Q

Zosyn:

Broad or Narrow Spectrum?

A

Broad

108
Q

Zosyn:

Use Against which Bugs?

A

Drug-resistant gram-negative infection, pseudomonas (also, broad gram-positive and anaerobic coverage)

109
Q

Zosyn:

Toxicity

A

Pseudomembranous colitis, increased LFTs, increased BIli

110
Q

Zosyn:

Drug of Choice for which Infection?

A

NEC

111
Q

Zosyn:

Does it cross the blood-brain barrier?

A

Yes

112
Q

Azithromycin:

What bug do we use it against and where does it grow from?

A

Ureaplasma which grows out of tracheal apsirates

113
Q

Azithromycin:

Mechanism of Action

A

Binds 50S ribosomal subunits inhibiting protein synthesis

114
Q

Azithromycin:

Toxicity

A

Increased LFTs, drug interactions with arrhythmias

115
Q

Amphotericin B:

Use Against which Bugs?

A

Fungal infection: Candida

116
Q

Amphotericin B:

Mechanism of Action

A

Binds ergosterol altering cell membrane permeability causing leakage of cell components and cell death

117
Q

Amphotericin B:

Toxicity

A

Fever, chills, agitation, hypotension, hypokalemia, hypomagnesium, renal failure, renal tubular acidosis, decreased hematocrit, rare thrombocytopenia

118
Q

Amphotericin B:

Does it cross the blood-brain barrier?

A

No

119
Q

Amphotericin B:

How long to give a treatment?

A

30 days following a negative culture

120
Q

Amphotericin B:

Caution with serum creatinine

A

Hold for two days if serum creatinine rises above 0.4mg/dL

121
Q

Amphotericin B:

Fluid Incompatibility

A

Not compatible with TPN and is also a four hour infusion time

122
Q

Fluconazole:

Use Against which Bugs?

A

Fungal infection: Candida (preferred over amphotericin)

123
Q

Fluconazole:

Mechanism of Action

A

Interferes with fungal cytochrome P450 sterol c-14-alpha-demethylation which decreases ergosterol synthesis inhibiting cell membrane formation

124
Q

Fluconazole:

Toxicity

A

Feeding intolerance, diarrhea, increased LFTs (less toxic than Amphotericin B)

125
Q

Fluconazole:

Does it cross the blood-brain barrier?

A

Yes

126
Q

Fluconazole:

Metabolism?

A

Hepatic metabolism - lots of drug interactions

127
Q

Voriconazole:

Use Against which Bugs?

A

Refractory fungal infections

128
Q

Voriconazole:

Mechanism of Action

A

Interferes with fungal cytochrome P450 sterol c-14-alpha-demethylation which decreases ergosterol synthesis inhibiting cell membrane formation

129
Q

Voriconazole:

Toxicity

A

Feeding intolerance, diarrhea, increased LFTs

130
Q

Voriconazole:

Metabolism

A

Hepatic P450 interactions

131
Q

Caspofungin:

Use Against which Bugs?

A

Refractory fungal infections

132
Q

Caspofungin:

Mechanism of Action

A

Inhibits synthesis of beta D-glucan, an essential fungi cell wall component

133
Q

Caspofungin:

Toxicity

A

Hypokalemia, hypercalcemia, hepatic impairment, anemia, decreased hemoglobin, neutropenia, bronchospasm

134
Q

Caspofungin:

How long is the treatment?

A

30 days

135
Q

Caspofungin:

Labs to Monitor

A

LFTs, potassium, CBC (lower hemoglobin)

136
Q

Caspofungin:

Metabolism

A

Hepatic

137
Q

Caspofungin:

Does it cross the blood-brain barrier?

A

Somewhat

138
Q

Acyclovir:

Use against what Virus?

A

Neonatal HERPES or suspected herpes

If meningitis without hypoxia at birth (seizure type activity, consider putting on acyclovir (evidence of herpes), or if lesions are evident (herpes rash).

139
Q

Acyclovir:

Mechanism of Action

A

Converted to triphosphate which competes with deoxyguanosine triphosphate for viral DNA polymerase and incorporates into viral DNA, thus inhibiting DNA synthesis

140
Q

Acyclovir:

Toxicity

A

Nephrotoxicity (rate-dependent), crystalluria, phlebitis at IV site (concentration dependent)

141
Q

Acyclovir:

Does it cross the blood-brain barrier?

A

yes

142
Q

Acyclovir:

Fluid level to prevent Nephrotoxicity

A

Baby has to be on 80mL/kg/day to ensure hydrated kidneys

143
Q

Ganciclovir:

Use Against which Virus?

A

CMV to decrease hearing loss

144
Q

Ganciclovir:

Mechanism of Action

A

Acyclic nucleoside analog of guanine

145
Q

Ganciclovir:

Toxicity

A

Anemia, thrombocytopenia, significant NEUTROPENIA IN MAJORITY of patients

If neutropenia issues are present, decrease the dose 50%. If neutropenia does not resolve, then discontinue.

146
Q

Ganciclovir:

Infusion Considerations

A

Avoid direct contact with the medication, treat as a cytotoxic drug (DON’T LET PREGNANT WOMEN HANDLE)

Complex infusion with specific tubing and filter

147
Q

Valganciclovir:

Oral Treatment for Ganciclovir. Treatment course?

A

60 days at home, and continues to improve hearing at 24 months

148
Q

Valganciclovir:

Use Against which Virus?

A

CMV

149
Q

Valganciclovir:

Mechanism of Action

A

Prodrug to Ganciclovir (improves bioavailability)

150
Q

Valganciclovir:

Toxicity

A

Anemia, thrombocytopenia, neutropenia, bone marrow suppression, potential carcinogen

151
Q

Mother to Child HIV transmission:

Which Triple Therapy?

A

Zidovudine
Lamivudine
Raltegravir (if less than 37 weeks then use Nevirapine instead)

152
Q

Zidovudine:

Use Against?

A

HIV transmission

153
Q

Zidovudine:

Mechanism of Action

A

Converted to a triphosphate which substitutes for deoxythymidine triphosphate for incorporation by reverse transcriptase inhibiting DNA synthesis

154
Q

Zidovudine:

Toxicity

A

Anemia, neutropenia (dose-dependent

155
Q

Zidovudine:

When to Start?

A

Within 6-12 hours of birth of known HIV exposure.

156
Q

Lamivudine:

Use Against?

A

HIV transmission

157
Q

Lamivudine:

Mechanism of Action

A

Converted to a triphosphate which substitutes for deoxythymidine triphosphate for incorporation by reverse transcriptase inhibiting DNA synthesis

158
Q

Lamivudine:

Dose

A

2 mg/kg PO q12h

At four weeks, increase to 4 mg/kg PO q12h

159
Q

Raltegravir:

Use Against?

A

HIV transmission

160
Q

Raltegravir:

Mechanism of Action

A

Integrase inhibitor

161
Q

Raltegravir:

Benefits

A

Greater viral suppression and less toxicity than non-nucleoside reverse transcriptase inhibitors in naive adults (not a lot of drug exposures)

162
Q

Raltegravir:

Contraindications

A

Less than 37 weeks

163
Q

Raltegravir:

Toxicity

A

Increase in LFTs, Hyperglycemia, neutropenia

RARE: rash, steven-johnson syndrome, and epidermal necrolysis

164
Q

Raltegravir:

Dose

A

PNA <8 days: 1.5 mg/kg PO q24h
PNA 8-28 days: 3 mg/kg PO q12h
PNA >28days: 6mg/kg PO q12h

Hold first dose 24-48 hours post-delivery if mom has received this medication within 24 hours of delivery

Neonatal Pharmacology - Fall 2021 (6 decks)

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