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Bacteriology > Antimicrobials > Flashcards

Antimicrobials Flashcards

1
Q

Define beta-lactams

A

Antibiotics that contain a beta-lactam ring in their molecular structure

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2
Q

Name the 4 types of penicillins

A

Natural
Anti-staphylococcal
Aminopenicillins
Antipseudomonal

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3
Q

Name 2 natural penicillins

A

Penicillin G
Penicillin V

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4
Q

Name 3 anti-staphylococcal penicillins

A

Oxacillin
Nafcillin
Dicloxacillin

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5
Q

Name 2 aminopenicillins

A

Amoxicillin
Ampicillin

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6
Q

Name 2 antipseudomonal penicillins

A

Piperacillin
Ticarcillin

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7
Q

Name the 4 carbapenems

A

Imipenem
Meropenem
Ertapenem
Doripenem

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8
Q

Name a monobactam

A

Aztreonam

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9
Q

Give examples of 1st generation cephalosporins

A

Cefadroxil
Cefalexin
Cefazolin
Cefazedone

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10
Q

Give examples of 2nd generation cephalosporins

A

2nd graders wear fake fox fur to tea parties

Cefaclor
Cefoxitin
Cefuroxime
Cefotetan

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11
Q

Give examples of 3rd generation cephalosporins

A

Cefixime
Ceftriaxone
Cefdinir
Cefodizine
Cefotaxime
Ceftazadime

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12
Q

Give examples of 4th generation cephalosporins

A

Cefepime
Cefquinome

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13
Q

Give examples of 5th generation cephalosporins

A

Ceftaroline
Ceftobiprole
Ceftolozane

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14
Q

Are beta-lactams bactericidal/bacteriostatic?

A

Bactericidal

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15
Q

Discuss the mechanism of action of beta-lactams

A
  1. Inhibit cell wall synthesis
    - mimics D-ala-D-ala structure of bacterial peptidoglycan residue
    - irreversibly binds to PBPs which act as transpeptidases -> stalled peptidoglycan cross linking -> inability to synthesize new cell wall -> bacterial death
  2. Activate autolytic enzymes
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16
Q

Which beta lactams have good CNS penetration?

A

Ceftriaxone
Aztreonam

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17
Q

When could beta-lactams other than ceftriaxone and aztreonam have CNS penetration?

A

Inflammation of the meninges -> disruption of the blood-brain-barrier

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18
Q

How are beta-lactams excreted?
Name exceptions.

A

Primarily renal
Exceptions
- nafcillin (biliary)
- anti-staphylococcal penicillins (renal and biliary)
- ceftriaxone (renal and biliary)

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19
Q

Name potential adverse effects of beta-lactams

A

Hypersensitivity reactions
Jarisch-Herxheimer reaction (syphilis)

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20
Q

Which organisms usually produce beta-lactamases?

A

Gram negative
Anaerobic

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21
Q

Give examples of beta lactamase inhibitors

A

Clavulanate
Avibactam
Sulbactam
Tazobactam

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22
Q

What is the other name for penicillin G?

A

Benzylpenicillin

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23
Q

What are the forms of penicillin G?

A

IV - crystalline penicillin
IM - procaine penicillin, benzathine penicillin

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24
Q

What is the other name for penicillin V?

A

Phenoxymethylpenicillin

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25
Q

What is the spectrum of cover of natural penicillins?

A

Gram +ve aerobes
Gram -ve cocci
Spirochetes
Branching gram +ve anaerobes

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26
Q

Name adverse effects of natural penicillins

A

Hypersensitivity reactions
Hemolytic anemia
Drug-induced interstitial nephritis
Seizures

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26
Q

How can natural penicillins

A

Penicillins bind to the bacterial breakdown products that form haptens -> formation of antibodies (anti-IgG) that trigger hemolysis with a positive direct Coombs test

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27
Q

Name the mechanisms of penicillin resistance

A

Penicillinases
PBP mutations

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27
Q

Name penicillinase-resistant penicillins

A

Nafcillin
Dicloxacillin
Oxacillin
Floxacillin
Methicillin

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27
Q

Why is methicillin no longer adminstered?

A

High rate of side effects

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27
Q

What characteristics of penicillinase-resistant penicillins allow them to be intrinsically beta-lactamase resistant?

A

Addition of bulky side chains e.g. isoxazolyl which prevent the beta-lactam ring from being hydrolysed

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28
Q

The penicillinase-resistant penicillins are broad/narrow spectrum?

A

Narrow spectrum

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29
Q

Name the mechanisms of resistance to penicillinase-resistant penicillins

A

Alteration of PBP binding site

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30
Q

Which aminopenicillin has a greater oral bioavailability?

A

Amoxicillin > ampicillin

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31
Q

What is the spectrum of cover of aminopenicillins?

A

“Extended-spectrum penicillin”

Gram +ve aerobes
Gram -ve bacilli

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32
Q

Which gram -ve bacilli are aminopenicillins not effective against?

A

Enterobacter spp.

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33
Q

Name adverse effects of aminopenicillins

A

Diarrhea
Pseudomembranous colitis
Drug-induced rash (incorrectly diagnosed infectious mononucleosis)
Hypersensitivity reactions
Acute interstitial nephritis (rare)

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34
Q

What is the mechanism of resistance to aminopenicillins?

A

Penicillinases

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35
Q

What kind of antipseudomonal penicillin is piperacillin?

A

Ureidopenicillin (IV)

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36
Q

What kind of antipseudomonal penicillin is mezlocillin?

A

Ureidopenicillin (IV)

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37
Q

What is the spectrum of cover of antipseudomonal penicillins?

A

Gram -ve rods
Anaerobes
Gram +ve aerobes

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38
Q

Which gram +ve aerobe are antipseudomonal penicillins not effective against?

A

S. viridans

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39
Q

Which drug is usually added with imipenem and why?

A

Cilastatin
Inhibits dehydropeptidase, a renal tubular enzyme that metabolizes imipenem

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39
Q

What is the spectrum of cover of carbapenems

A

Gram +ve cocci
Gram -ve bacilli
Anaerobes

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39
Q

Which carbapenem has limited activity against pseudomonas?

A

Ertapenem

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40
Q

Which gram +ve cocci are intrinsically resistant to carbapenems?

A

MRSA
Enterococcus faecalis
Enterococcus faecium

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41
Q

Name adverse effects of carbapanems

A

Secondary fungal infections
CNS toxicity
GI upset
Rash
Thrombophlebitis

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42
Q

Which carbapenems carry the highest and lowest risk of CNS toxicity?

A

Highest risk - imipenem
Lowest risk - meropenem

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43
Q

Name bacteria that commonly produce carbapenemases

A

Keep Every Antibiotic, Protect Every Carbapenem!

Klepn
Ecoli
Aciba
Pseae
Enterobacter
Citfr

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44
Q

What are the special characteristics of aztreonam?

A

Bind to PBP3
Less susceptible to beta-lactamases

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45
Q

What is the spectrum of cover of monobactams?

A

Gram -ve bacteria
Can add vanco/clinda to create broad-spectrum coverage

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46
Q

Which beta-lactams are an alternative for penicillin allergic patients?

A

Monobactams (no cross sensitivity)

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47
Q

Name adverse effects of monobactams

A

GI upset
Injection reactions
Rash

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48
Q

Which generation of cephalosporins has the least activity against gram +ve bacteria?

A

3rd generation

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49
Q

Which gram -ve bacteria are covered by 1st generation cephalosporins?

A

Proteus mirabilis
E.coli
Klepn

1 PEcK

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50
Q

Which gram -ve bacteria are covered by 2nd generation cephalosporins?

A

Haem influenza
Enterobacter aerogenes
Neisseria
Serratia
Proteus mirabilis
E.coli
Klebs pneumo

2 HENS PEcK

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51
Q

Which generation of cephalosporins is active against MRSA?

A

5th generation

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52
Q

Which generation of cephalosporins is active against listeria?

A

5th generation

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53
Q

Which generation of cephalosporins is active against enterococcus?

A

5th generation

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54
Q

Which generation of cephalosporins is active against pseudomonas?

A

3rd and 4th generation

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55
Q

Name adverse effects of cephalosporins

A
  1. Penicillin allergy cross reactivity
  2. Autoimmune hemolytic anemia
  3. Vitamin K deficiency
  4. Disulfiram-like reaction
  5. Increases aminoglycoside nephrotoxic effect
  6. Neurotoxicity
  7. Hyperbilirubinemia (neonates)
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56
Q

What is the mechanism of hypoprothrombinemia secondary to cephalosporin use?

A

Not fully understood
Theories:
- inhibit growth of vitamin K producing intestinal bacteria
- inhibit enzymes of vitamin K metabolism

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57
Q

Explain drug-induced autoimmune hemolytic anemia

A

Drugs bind to RBC membrane proteins -> preformed anti-drug antibodies bind to drug-coated RBCs -> hemolysis in the spleen

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58
Q

What are the mechanisms of resistance to cephalosporins?

A

Cephalosporinase
PBP changes

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59
Q

Why are cephalosporins (1st-4th generation) LAME?

A

Ineffective against:
Listeria
Atypicals
MRSA
Enterococci

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60
Q

Are glycopeptides bactericidal/bacteriostatic?

A

Bactericidal

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61
Q

Which organism are glycopeptides bacteriostatic against?

A

C. diff

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62
Q

Give examples of glycopeptides

A

Vancomycin
Bacitracin
Teicoplanin
Telavancin
Dalbavancin
Oritavancin

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63
Q

What is the route of elimination of glycopeptides?

A

Renal via glomerular filtration

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64
Q

What is the spectrum of cover of glycopeptides?

A

Gram +ve bacteria
MRSA
S. epidermidis
Enterococci
C. diff

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65
Q

Name adverse effects of glycopeptides

A

Nephrotoxicity
Ototoxicity
Thrombophlebitis
Vancomycin flushing reaction
DRESS syndrome
Neutropenia
Dysgeusia
GIT upset

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66
Q

What is vancomycin flushing reaction?

A

Anaphylactoid reaction caused by rapid infusion of vancomycin -> nonspecific mast cell degranulation -> rapid histamine release

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67
Q

Which kind of vancomycin therapy is associated with neutropenia?

A

Prolonged (>7 days)

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68
Q

What does DRESS syndrome stand for?

A

Drug reaction with eosinophilia and systemic symptoms

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69
Q

Name contraindications for glycopeptides

A

Pregnancy

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70
Q

Name mechanisms of resistance to glycopeptides

A

Modification of D-ala-D-ala to D-ala-D-lac (mainly enterococcus)

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71
Q

What is the mechanism of action of epoxides?

A

Inhibits enolpyruvate transferase (MurA) -> no formation of N-acetylmuramic acid -> inhibition of cell wall synthesis

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72
Q

Epoxides are bactericidal/bacteriostatic?

A

Bactericidal

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73
Q

Name an epoxide

A

Fosfomycin

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74
Q

What is the route of elimination of fosfomycin?

A

Renal

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75
Q

Name adverse effects of fosfomycin

A

Mild electrolyte imbalances (hypernatremia, hyopkalemia)
Diarrhea

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76
Q

What is the mechanism of resistance to fosfomycin?

A

MurA mutations

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77
Q

Give an example of a lipopeptide

A

Daptomycin

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78
Q

What is the mechanism of action of daptomycin?

A

Incorporates K+ channels into the cell membrane of gram +ve bacteria -> rapid membrane depolarization -> loss of membrane potential -> inhibition of DNA, RNA and protein synthesis

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79
Q

Daptomycin is bactericidal/bacteriostatic?

A

Bactericidal

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80
Q

What is the route of elimination of daptomycin?

A

Renal

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81
Q

What is the spectrum of cover of daptomycin?

A

Gram +ve bacteria
MRSA
VRE

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82
Q

What are the main sites in the body that daptomycin is effective?

A

Skin
Blood
Heart

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83
Q

Why can daptomycin not be used for pneumonias?

A

It is bound and inactivated by surfactant

84
Q

Name adverse effects of daptomycin

A

Reversible myopathy
Rhabdomyolysis
Allergic pneumonitis

85
Q

What is the mechanism of resistance to daptomycin?

A

Repulsion of daptomycin molecules due to change in bacterial surface charge

86
Q

Give examples of polymyxins

A

Polymyxin E = colistin
Polymyxin B

87
Q

What kind of molecule are polymyxins?

A

A cationic detergent (polypeptide) molecule

88
Q

What is the mechanism of action of colistin?

A

Binds to phospholipids (LPS endotoxin) of the cytoplasmic membrane of gram -ve bacteria -> increase membrane permeability -> leakage of cell contents

89
Q

What is the route of elimination of colistin?

90
Q

How can polymyxin B be used for superficial skin infections?

A

Triple antibiotic ointment
- bacitracin
- neomycin
- polymyxin B

91
Q

How can polymyxin B be used to prevent ICU infections?

A

May be used to disinfect the bowel

92
Q

Name adverse effects of colistin

A

Nephrotoxicity
Neurotoxicity
Anaphylactoid reactions
Respiratory failure

93
Q

Give examples of aminoglycosides

A

Gentamycin
Amikacin
Tobramycin
Streptomycin
Neomycin
Capreomycin
Kanamycin

94
Q

What is the mechanism of action of aminoglycosides?

A

Bind to 30S subunit of bacterial ribosome -> irreversible inhibition of initiation complex -> inhibition of bacterial protein synthesis

95
Q

With which drug class are aminoglycosides synergistic?

A

Beta-lactams inhibit cell wall synthesis to facilitate entry of aminoglycoside drugs into the cytoplasm

96
Q

What is the route of elimination of aminoglycosides?

A

Renal via glomerular filtration

97
Q

What is the spectrum of cover of aminoglycosides?

A

Gram -ve bacilli

98
Q

Why are aminoglycosides not effective against anaerobes?

A

Require oxygen to be absorbed by cells

99
Q

Name adverse effects of aminoglycosides

A

Nephrotoxicity
Ototoxicity
Vestibulotoxicity
Neuromuscular blockade
Teratogenecity

100
Q

Concurrent use with which drugs increase the risk of ototoxicity secondary to aminoglycoside use?

A

Loop diuretics

101
Q

Name contraindications for aminoglycosides

A

Myasthenia gravis
Botulism
Pregnancy

102
Q

What are the mechanisms of resistance to aminoglycosides?

A

Bacterial transferase enzyme inactivation via
- acetylation
- phosphorylation
- adenylation

103
Q

Give examples of tetracyclines

A

Minocycline
Tetracycline
Doxycycline
Demeclocyline

104
Q

What is the mechanism of action of tetracyclines?

A

Bind 30s subunit -> aminoacyl-tRNA is blocked from binding to ribosome acceptor site -> inhibition of bacterial protein synthesis

105
Q

Are tetracyclines bactericidal/bacteriostatic?

A

Bacteriostatic

106
Q

What is the route of elimination of tetracyclines?

107
Q

Which tetracycline is not contraindicated in patients with renal failure and why?

A

Doxycycline - only gastrointestinal elimination

108
Q

What is the spectrum of cover of tetracyclines?

A

Atypical bacteria
Community-acquired MRSA

109
Q

Which substances should oral tetracyclines not be taken with and why?

A

Any substance containing large amounts of divalent cations which inhibit intestinal absorption of tetracyclines

110
Q

Name adverse effects of tetracyclines

A

Hepatotoxicity
Teeth and bone changes
Mucous membrane damage (esophagitis)
Photosensitivity
Fanconi syndrome
Pseudotumor cerebri

111
Q

Why do tetracyclines cause photosensitivity?

A

Tetracyclines absorb UV radiation -> photochemical reaction -> free radical formation -> damage to cellular components -> inflammation

112
Q

Give contraindications to tetracyclines

A

Children <8yo
Pregnant/breastfeeding women
Renal failure
Hepatic dysfunction

113
Q

What is the mechanism of resistance to tetracyclines?

A

Plasmid-encoded efflux pumps

114
Q

Give an example of a glycylcycline

A

Tigecycline

115
Q

What is the mechanism of action of tigecycline?

A

Binds to 30S subunit -> blockage of entry of amino-acyl tRNA into ribosomal A site -> inhibition of protein synthesis

116
Q

What is the route of elimination of tigecycline?

A

Mostly biliary

117
Q

What is the spectrum of cover of tigecycline?

A

Gram positive aerobes
Gram negative aerobes
MRSA
VRE
Anaerobes
Non-gram staining bacteria

118
Q

Which gram positive aerobes is tigecycline not effective against?

A

S. viridans
Enterococci
MSSA

119
Q

Which gram negative aerobes is tigecycline not effective against?

120
Q

Name adverse effects of tigecycline

A

GI upset
Hepatotoxicity
Teeth and bone deposition
Photosensitivity

121
Q

What are the contraindications to tigecycline?

A

Children <8yo
Pregnant/breastfeeding women
Hepatic dysfunction

122
Q

Give examples of macrolides

A

Erythromycin
Azithromycin
Clarithromycin
Roxithromycin

123
Q

What is the mechanism of action of macrolides?

A

Bind to 23S ribosomal RNA molecule of 50S subunit -> blockage of translocation -> inhibition of bacterial protein synthesis

124
Q

What is the route of elimination of macrolides?

125
Q

What is the spectrum of cover of macrolides?

A

Atypical pneumonias
Bordetella
Chlamydia
Gram +ve cocci
Neisseria
Mycobacterium avium (azithro)
H. pylori
Ureaplasma urealyticum
Babesia spp. (azithro + atovaquone)

126
Q

Name adverse effects of macrolides

A

Increased intestinal motility
QT prolongation
Arrythmias
Acute cholestatic hepatitis
Eosinophilia
Rash
HPS risk in infant <6w

127
Q

Which drugs does erythromycin interact with?

A

All affected by CYP450

128
Q

Which macrolide does not have a short half life?

A

Azithromycin

129
Q

What can erythromycin be used off label for?

A

Gastroparesis (increases intestinal motility)

130
Q

Which macrolides are contraindicated in pregnant women?

A

Erythromycin estolate
Clarithromycin

131
Q

What is erythromycin estolate use in pregnant women during the 1st trimester associated with?

A

Hepatic failure

132
Q

Can erythromycin forms other than erythromycin estolate be used in pregnant women?

A

Yes (ethyl succinate, stearate)

133
Q

Which macrolide must be used cautiously in patients with renal failure?

A

Clarithromycin

134
Q

What is the mechanism of resistance to macrolides?

A

Methylation of the binding site of 23S rRNA -> macrolide cannot bind to rRNA

135
Q

What bacterial class is clindamycin?

A

Lincosamides

136
Q

What is the mechanism of action of clindamycin?

A

Binds to 50s subunit to block peptide translocation -> inhibition of peptide chain elongation -> inhibition of bacterial protein synthesis

137
Q

What the route of elimination of clindamycin?

A

Renal and biliary

138
Q

What is the spectrum of cover of clindamycin?

A

Anaerobes
Gram +ve aerobes
Babesia (with quinine)

139
Q

What does clindamycin share cross resistance with?

A

Macrolides

140
Q

Name adverse effects of clindamycin

A

GI upset
Pseudomembranous colitis
Fever
Teratogenicity

141
Q

Give examples of streptogramins

A

Dalfopristin
Quinupristin

142
Q

What is the mechanism of action of dalfopristin?

A

Binds to 23S portion of 50S subunit -> change conformation -> enhanced binding of quinupristin and inhibits peptidyl transferase

143
Q

What is the mechanism of action of quinupristin?

A

Binds to 50S subunit -> prevents elongation of polypeptide -> incomplete chains released

144
Q

What is the route of elimination of streptogramins?

A

Biliary and renal

145
Q

What is the spectrum of cover of streptogramins?

A

Skin infections
- staph
- strep
- VRE

146
Q

Which enterococcus are streptogramins NOT effective against?

A

Enterococcus faecalis

147
Q

Which cytochrome is inhibited by streptogramins?

148
Q

Name adverse effects of streptogramins

A

GI upset
Headache
Arthralgia
Myalgia
Thrombophlebitis
Pseudomembranous colitis
Pruritis (rare)

149
Q

Has safety been establish for streptogramins in pregnant/breastfeeding women or children <16yo?

150
Q

Name mechanisms of resistance to streptogramins

A

Modification of ribosome binding site
Enzyme-mediated methylation
Efflux pumps

151
Q

Which drug class does linezolid belong to?

A

Oxazolidinones

152
Q

What is the mechanism of action of linezolid?

A

Binds to 23S RNA of 50S subunit -> inhibition of initiation complex formation -> inhibition of bacterial protein synthesis
Non-selective MAOI

153
Q

Against which bacteria is linezolid bactericidal?

A

Streptococci

154
Q

What is the CNS penetration of linezolid?

155
Q

What is the route of elimination of linezolid?

A

Hepatic metabolism
Biliary and renal elimination

156
Q

Name adverse effects of linezolid

A

GI upset
Pancytopenia
Peripheral neuropathy
Serotonin syndrome

157
Q

Give contraindications for linezolid

A

SSRIs
Selective MAOIs

158
Q

Name mechanism of resistance to linezolid

A

Point mutation of 23S rRNA

159
Q

What is the mechanism of action of chloramphenicol?

A

Binds to 50S subunit -> blockage of peptidyltransferase -> inhibition of bacterial protein synthesis

160
Q

What is the CNS penetration of chloramphenicol?

161
Q

What is the route of elimination of chloramphenicol?

A

Hepatic metabolism
Renal elimination

162
Q

What is the spectrum of cover of chloramphenicol?

A

Meningitis
Rickettsia

163
Q

Which cytochromes does chloramphenicol inhibit?

A

CYP2C19
CYP3A4

164
Q

Name adverse effects of chloramphenicol

A

Dose dependent BM suppression
Gray baby syndrome

165
Q

What is the mechanism of resistance in chloramphenicol?

A

Drug inactivation via plasmid-encoded acetyltransferase

166
Q

Give examples of 1st generation fluoroquinolones

A

Nalidixic acid

167
Q

Give examples of 2nd generation fluoroquinolones

A

Ciprofloxacin
Norfloxacin
Ofloxacin
Enoxacin

168
Q

Give examples of 3rd generation fluoroquinolones

A

Levofloxacin

169
Q

Give examples of 4th generation fluoroquinolones

A

Moxifloxacin
Gemifloxacin
Gatifloxacin

170
Q

Which is the only fluoroquinolone also available in IV form?

A

Levofloxacin
Enoxacin

171
Q

What is the mechanism of action of fluoroquinolones?

A

Inhibition of prokaryotic topoisomerase II and IV -> DNA supercoiling -> formation of double-stranded breaks -> inhibition of DNA replication and transcription

172
Q

What is the CNS penetration of fluoroquinolones?

173
Q

What is the route of elimination of fluoroquinolones?

A

Renal via glomerular filtration and tubular secretion

174
Q

Which fluoroquinolone undergoes biliary excretion?

A

Moxifloxacin

175
Q

Which substances reduce fluoroquinolone absorption?

A

Polyvalent cations

176
Q

Name the “respiratory” fluoroquinolones

A

Levofloxacin
Moxifloxacin
Gemifloxacin

177
Q

What is the spectrum of cover of the non-respiratory fluoroquinolones?

A

Gram -ve rods (urinary, GI)
Genitourinary infections (gonorrhoeae, chlamydia, ureaplasma)

178
Q

Which flouroquinolone is effective against pseudomonas?

A

Ciprofloxacin

179
Q

What is the spectrum of cover of the respiratory fluoroquinolones?

A

Atypical bacteria
Anaerobes

180
Q

Which fluoroquinolone is highly potent against penicillin-resistant pneumococci?

A

Gemifloxacin

181
Q

Name adverse effects of fluoroquinolones

A

GI upset
Neurological
Hypo/hyperglycemia
QT prolongation
Photosensitivity
Superinfection
Tendon rupture
Life threatening exacerbation of myasthenia gravis

182
Q

What neurological adverse effects can be caused by fluoroquinolones?

A

Headache
Dizziness
Mood changes
Peripheral neuropathy
Lower seizure threshold

183
Q

Which factors increase risk for lower seizure threshold with fluoroquinolones?

A

NSAID use
Prev epilepsy hx

184
Q

Which cytochrome do fluoroquinolones inhibit?

185
Q

Name mechanisms of resistance to fluoroquinolones

A

Chromosome encoded mutations in DNA gyrase and topoisomerase IV enzymes
Altered cell wall permeability
Plasmid-encoded mutations in efflux pump proteins

186
Q

Give examples of nitroimidazoles

A

Metronidazole
Tinidazole

187
Q

What is the mechanism of action of metronidazole?

A

Creates free radicals within bacterial cell -> DNA strand breakage -> cell death

188
Q

What is the CNS penetration of metronidazole?

189
Q

What is the route of elimination of metronidazole?

190
Q

What is the spectrum of cover of metronidazole?

A

Some protozoa (giardia, tricho, entamoeba)
Anaerobes
Facultative anaerobes

191
Q

Name adverse effects of metronidazole

A

Headache
Metallic taste
Peripheral neuropathy
Vestibular dysfunction

192
Q

Can nitroimidazoles cause disulfiram-like reactions?

A

Disproved despite case reports
Metronidazole does not inhibit acetaldehyde dehydrogenase
Possible explanations - change in gut flora, histamine reactions

193
Q

Give examples of diaminopyrimidine derivatives

A

Trimethoprim
Pyrimethamine

194
Q

Give examples of antibiotic sulfonamides

A

Sulfamethoxazole
Sulfadiazine
Sulfisoxazole

195
Q

Give examples of non-antibiotic sulfonamides

A

Diuretics (thiazides, furosemide, acetazolamide)
Anti-inflammatory drugs (celecoxib)
Sulfonylureas
Probenecid

196
Q

What is the mechanism of action of trimethoprim versus sulfamethoxazole?

A

Both inhibit bacterial folic acid synthesis

Trimethoprim - inhibits dihydrofolate reductase (DHFR)
Sulfamethoxazole - inhibits dihydropteroate synthase

197
Q

What is the CNS penetration of TMP-SMX?

198
Q

What is the route of elimination of TMP-SMX?

A

Primarily renal via tubular secretion

199
Q

What is the spectrum of cover of TMP-SMX?

A

Shigella
Salmonella
Empiric UTI treatment
Prophylaxis (P. jirovecii, toxoplasmosis)

200
Q

What is the spectrum of cover of sulfisoxazole?

A

Broad spectrum gram +ve and -ve
N. meningitidis
Chlamydia trachomatis
Nocardia asteroides
Toxoplasma gondii
Plasmodia

201
Q

Name adverse effects of sulfonamides

A

CYP450 drug interactions
Kernicterus (infants)
Nephrotoxicity
GI upset
Hyperkalemia
Agranulocytosis
Pancytopenia
Hemolytic anemia
Steven Johnson’s
Photosensitivity
Fever

202
Q

What is the most common form of nephrotoxicity secondary to sulfonamide use?

A

Acute tubulointerstitial nephritis

203
Q

In which patients can sulfonamides trigger hemolytic anemia?

A

G6PD-deficiency

204
Q

Name adverse effects of trimethoprim

A

Megaloblastic anemia
Leukopenia
Granulocytopenia
Hyperkalemia
Increased creatinine

205
Q

How does trimethoprim cause hyperkalemia?

A

Competitive inhibition of ENaC channels in the distal convoluted tubule -> decreased NA reabsorption -> decreased K secretion

206
Q

What are the mechanisms of resistance to sulfonamides?

A

Mutation in bacterial dihydropteroate synthase
Increased PABA synthesis
Decreased sulfonamide uptake

207
Q

Which drug class does nitrofurantoin belong to?

A

Nitrofurans

208
Q

What is the mechanism of action of nitrofurantoin?

A

Reduced by bacterial nitroreductases to reactive metabolites -> bind to ribosome -> impaired metabolism + synthesis of protein, DNA, RNA -> cell death

209
Q

What is the route of elimination of nitrofurantoin?

A

Primarily renal
Minimal in the feces

210
Q

What is the spectrum of cover of nitrofurantoin?

A

UTI pathogens (gram +ve and -ve)

211
Q

Which UTI pathogens is nitrofurantoin NOT effective against?

A

Pseudomonas
Proteus

212
Q

Can nitrofurantoin be used in pyelonephritis?

A

No! It does not achieve adequate concentrations in renal tissue.

213
Q

Name adverse effects of nitrofurantoin

A

Nitrofurantoin-induced lung disease (NILD)
Pulmonary fibrosis
Hemolytic anemia in G6PD deficiency
GI upset
Reversible peripheral neuropathy

214
Q

Distinguish between acute vs chronic NILD

A

Acute = hypersensitivity reaction usually 9 days after exposure
Chronic = cell-mediated or toxic reaction usually 6 months after exposure

215
Q

Name contraindications for nitrofurantoin

A

Children <1mo
Breastfeeding women
Women GA 38-42w
Hepatic dysfunction
eGFR <60

Bacteriology (4 decks)

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