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Bacteriology > Antimicrobials > Flashcards

Antimicrobials Flashcards

1
Q

What are the agent(s) of the folate anti-metabolites class?

A

Trimethoprim-sulfamethoxazole (sulfonamides and trimethoprim rarely used separately)

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2
Q

What is the mechanism of action of folate anti-metabolites?

A

Prevent production of tetrahydrofolate for synthesis of purines and thymidine

  • Sulfonamide inhibits dihydropteroate synthetase
  • Trimethoprim inhibits dihydrofolate reductase
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3
Q

What is the spectrum of activity for folate anti-metabolites?

A

Traditionally used for Gram negatives
Some Gram positive activity including S. aureus
Some protozoa and fungi

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4
Q

What are common adverse events of folate anti-metabolites?

A

Common: nausea, vomiting, headache, rash
Rare: Stevens-Johnson syndrome, drug interactions

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5
Q

What are the major clinical uses of folate anti-metabolites?

A

UTI and respiratory infections

Increasing use for S. aureus

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6
Q

What are the agent(s) of the quinolones (and fluoroquinolones)?

A

Ciprofloxacin, Moxifloxacin

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7
Q

What is the mechanism of action of the quinolones?

A

Form complex with DNA and topoisomerase II or IV, preventing the topoisomerase from fixing the DNA double strand breaks

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8
Q

What are the mechanisms of resistance of folate anti-metabolites?

A

Genetic mutation

Plasmid (containing alternate dhfr allele in the case of trimethoprim)

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9
Q

What are the mechanisms of resistance of quinolones?

A

Mutations in target enzyme (topoisomerase)

Efflux pumps

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10
Q

What are common adverse effects of quinolones?

A

Common: GI intolerance, headache, nervousness
Rare:
Seizures
May prolong QT interval in patients taking other medications that can prolong QT
Tendon rupture

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11
Q

What is the spectrum of activity of quinolones?

A

Active against most Gram negatives and “atypicals” (Mycoplasma, Chlamydia, Legionella, Mycobacteria)

Moxifloxacin is also active against Gram positive Strep and anaerobes

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12
Q

What are the clinical uses of quinolones?

A

GI infections
Ciprofloxacin - UTIs
Moxifloxacin - Pneumonia, mycobacterial infections, polymicrobial infections due to anaerobic activity

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13
Q

What is the spectrum of activity of Nitrofurantoin?

A

Gram-pos and Gram-neg uropathogens (Staph, Strep, Enterococcus, Klebsiella)

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14
Q

What are the clinical uses of Nitrofurantoin?

A

Only used for UTI

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15
Q

What agent(s) are in the Rifamycins class?

A

Rifampin
Rifabutin
Rifaximin

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16
Q

What is the mechanism of action of rifamycins?

A

Binds beta subunit of RNA polymerase and blocks transcription

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17
Q

What is unique about the pharmacology/kinetics of rifamycins?

A

Metabolized by P450 3A4

  • Rafampin: potent induced, can increase metabolism of other drugs
  • Rifabutin: levels can rise in presence of P450 inhibitors
  • Rifaximin: not absorbed, only taken PO
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18
Q

What are common adverse events of rifamycins?

A

Turns secretions orange!
GI intolerance
Hematologic or hepatic toxicity

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19
Q

What is the spectrum of activity of rifamycins?

A

Very broad, includes Gram pos, Gram neg, anaerobic and mycobacterial

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20
Q

What are the clinical uses of rifamycins?

A

Prophylaxis (for Neisseria)
Used in combination with other antimicrobials, i.e. in the treatment of Mycobacterial TB infection

Rifaximin: just treats GI infections since poorly absorbed

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21
Q

What is the spectrum of activity of Fidaxomicin?

A

Only Gram-positive bacteria

But also has less dramatic effect on fecal microbiome than other agents

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22
Q

What are the clinical uses of Fidaxomicin?

A

C. diff colitis

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23
Q

What antimicrobials fall under the category of Beta-lactam agents?

A

Penicillins
Cephalosporins
Carbapenems
Monobactams

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24
Q

What are mechanisms of resistance of Penicillins?

A

Beta-lactamase

Modified Penicillin-binding proteins (e.g. e.g. PBP2A encoded by the mecA gene which results in methicillin-resistant Staphylococcus aureus (MRSA), with a decreased affinity for β-lactam antibiotics)

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25
Q

What are the common adverse events of Penicillins?

A 
Hypersensitivity reactions (rashes, serum sickness)
At high concentrations: seizures
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26
Q

What are the classes of Penicillins?

A

Penicillin G (and V)
Semi-synthetic penicillins
Aminopenicillins
“Antipseudomonal” penicillins

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27
Q

What is the spectrum of activity of Penicillin G?

A

Gram positive cocci and anaerobes
Gram negative cocci
Spirochetes (syphilis)

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28
Q

What are the clinical uses of Penicillin G?

A

Infections caused by most Streptococci (if susceptible)
Gram positive anaerobic infections (dental abscesses, bites)
Syphilis

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29
Q

What agents are in the class of semi-synthetic penicillins and are they IV or PO?

A

Nafcillin - IV

Dicloxacillin - PO

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30
Q

What is the spectrum of activity of semi-synthetic penicillins?

A

NO Gram negatives

ONLY Gram positive cocci and anaerobes

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31
Q

What are the clinical uses of semi-synthetic penicillins?

A

Infections due to methicillin-SUSCEPTIBLE S. aureus (MSSA)

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32
Q

What agents fall in the class of aminopenicillins and are they IV or PO?

A

Ampicillin - IV

Amoxicillin - PO

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33
Q

What is the spectrum of activity of aminopenicillins?

A

Gram positive cocci and anaerobes

Some Gram neg bacilli

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34
Q

What are the clinical uses of aminopenicillins?

A

Community-acquired HEENT and upper respiratory infections

Community-acquired UTIs

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35
Q

What agents fall in the class of “antipseudomonal” penicillins?

A

Piperacillin

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36
Q

What is the spectrum of activity of Piperacillin?

A

Includes highly-resistant Gram-neg bacilli like Pseudomonas

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37
Q

What are the clinical uses of Piperacillin?

A

NONE ON ITS OWN. Only used in combination with tazobactam as a beta-lactamase inhibitor

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38
Q

What is the mechanism of action of beta-lactamase inhibitors?

A

Bind and hydrolyze beta-lactamases while beta-lactams remain intact and exert effect

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39
Q

What agents fall under the class of beta-lactamase inhibitors?

A

Ampicillin-sulbactam
Amoxicillin-clavulanic
Piperacillin-tazobactam

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40
Q

What is the spectrum of activity of beta-lactamase inhibitors?

A

Very broad. Beta lactam combined with inhibitor covers:

  • Gram pos like S. aureus (but not MRSA)
  • Beta-lactamase producing Gram neg and anaerobes
  • Piperacillin-tazobactam also covers Pseudomonas!
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41
Q

What are the clinical uses of beta-lactamase inhibitors?

A

Polymicrobial infections or resistant infections

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42
Q

What is the mechanism of action of cephalosporins?

A

Beta-lactam

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43
Q

How do beta-lactam agents work?

A

Covalently bind transpeptidases involved in forming the peptide cross-links in the peptidoglycan, creating a weakened cell wall.
Autolysins will lyse cell.

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44
Q

What are the first generation cephalosporins?

A

Cefazolin

Cephalexin

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45
Q

What are the common adverse events of cephalosporins?

A

Minimal side effects
Hypersensitivity
Possible cross-reactivity with penicillin allergy

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46
Q

What is the spectrum of activity of first generation cephalosporins?

A

Gram positive Strep and Staph

Some Gram negative bacilli

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47
Q

What are the clinical uses of first generation cephalosporins?

A

Cefazolin - antimicrobial prophylaxis during surgery

Cephalexin - oral cephalosporin, usually skin and soft tissue infections from Strep and Staph (not MRSA)

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48
Q

What are the second generation cephalosporins?

A

Cefoxitin

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49
Q

What is the spectrum of activity of second generation cephalosporins?

A

Gram pos Strep and Staph
Excellent activity against Gram neg anaerobes
Increased activity against Gram neg bacilli

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50
Q

What are the clinical uses of second generation cephalosporins?

A

Treat intraabdominal infections or prophylaxis in intraabdominal surgery

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51
Q

What are the third generation cephalosporins?

A

Ceftriaxone, Ceftrazidime

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52
Q

What is the spectrum of activity of third generation cephalosporins?

A

Gram-pos Strep and Staph

Excellent activity against Gram neg cocci and bacilli (high degree of penetration into CSF)

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53
Q

What are the clinical uses of third generation cephalosporins?

A

Cefriaxone - meningitis, endocarditis and osteomyelitis, community-acquired pneumonia
Ceftazidime - covers Pseudomonas!

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54
Q

What are the mechanisms of resistance to cephalosporins?

A

More resistant to beta-lactamases (not much effect)
Intrinsic resistance (mostly enterococci and Pseudomonas)
Altered membrane permeability - Pseudomonas
Altered PBPs

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55
Q

What are the fourth generation cephalosporins?

56
Q

What is the spectrum of activity of fourth generation cephalosporins?

A

Broadest spectrum
Gram-positive Staph and Strep
Extremely active against Gram neg bacteria including Pseudomonas

57
Q

What are the clinical uses of fourth generation cephalosporins?

A

Pseudomonas

58
Q

What are the fifth generation cephalosporins?

A

Ceftaroline

59
Q

What is the spectrum of activity of ceftaroline?

A

Most Gram-pos (including MRSA but not enterococci)

Some Gram-neg (but not Pseudomonas)

60
Q

What are the clinical uses of ceftaroline?

A

MRSA treatment

61
Q

What agents are in the class of Carbapenems?

A

Imipenem

Ertapenem

62
Q

What is the mechanism of action of Carbapenems?

A

Beta-lactam

63
Q

What are the mechanism of resistance of Carbapenems?

A

Not much resistance
Resistance to most beta-lactamases
Some carbapenemases exist

64
Q

What are common adverse side effects of Carbapenems?

A

Hypersensitivity reactions
Seizures at high concentration
Possible cross-reactivity with penicillin allergy

65
Q

What is the spectrum of activity of Carbapenems?

A

Very broad
Gram pos (including Enterococcus faecalis)
Gram neg (including Pseudomonas, except when treating with Ertapenem)
Anaerobes

66
Q

What are the clinical uses of carbapenems?

A

Serious infections

Treatment of infections due to resistant bacteria

67
Q

What agents are in the class of Monobactams?

68
Q

What is the mechanism of action of aztreonam?

A

Beta-lactam

69
Q

What are the common adverse side effects of aztreonam?

A

Little cross-reactivity to penicillin or cephalosporin allergy

70
Q

What is the spectrum of activity of aztreonam?

A

Gram negative ONLY

No Gram positive

71
Q

What are the clinical uses of aztreonam?

A

Used as alternative for patients with penicillin/cephalosporin allergy

72
Q

What are the agents in the category of glycopeptides?

A

Vancomycin

73
Q

What is the mechanism of action of vancomycin?

A

Binds terminal D-alanine dipeptide of peptidoglycan, inhibits glycosyltransferase and transpeptidase

74
Q

What are mechanism of resistance of vancomycin?

A

Alteration of vancomycin binding site (encoded by vanA - vanE)
Thickened cell wall resulting in inability of antibiotic to penetrate

75
Q

What are common adverse side effects of vancomycin?

A

“Red Man” syndrome: flushing, redness, hypotension during infusion
Dose related ototoxicity
Nephrotoxicity (must monitor levels)

76
Q

What is the spectrum of activity of vancomycin?

A

Gram positive ONLY (including MRSA)

NO Gram negative

77
Q

What are clinical uses of vancomycin?

A

Inferior to beta lactams, but typically used for Gram-pos infections resistant to beta-lactams (MRSA)

Empiris treatment for serious Gram-pos infections

C. diff associated disease

78
Q

What agents are in the class of cyclic lipopeptides?

A

Daptomycin

79
Q

What is the mechanism of action of daptomycin?

A

Inserts lipophilic tail into cell membrane –> rapid membrane depolarization and efflux of K+

80
Q

What are the common adverse side effects of daptomycin?

A

GI upset, rash, headache
Elevation of creatine phosphokinase (CPK) and possible rhabdomyolysis associated with higher dosing
- Should monitor CPK levels

81
Q

What is the spectrum of activity of daptomycin?

A

Gram pos (includes MRSA and VRE)
Gram pos anaerobes
NO Gram neg activity

82
Q

What are the clinical uses of daptomycin?

A

Complicated skin and soft tissue infections, bacteremia, endocarditis

83
Q

What is the mechanism of action of polymixins?

A

Bind LPS and disrupt outer membrane

84
Q

What are common adverse effects of polymixins?

A

Significant toxicities (nephrotoxicity, neurotoxicity, bronchospasm)

85
Q

What is the spectrum of activity of polymixins?

A

ONLY Gram neg bacilli

Reemerged in usage despite toxicity due to strains of Acinetobacter and Pseudomonas resistant to all other agents

86
Q

What are the clinical uses of polymixins?

A

Serious resistant Gram neg infections, pneumonia

87
Q

What is the spectrum of activity of Bacitracin?

A

Gram pos ONLY

88
Q

What are the clinical uses of Bacitracin?

A

Ointments (topical), often in combination with other antimicrobials

89
Q

What are the clinical uses of Fosfomycin?

A

UTI only (in an oral powder)

90
Q

What antimicrobials fall under the classification of Protein Synthesis Inhibitors?

A 
Aminoglycosides
Tetracyclines
Glycyclines
Macrolides
Lincosamides
Oxazolidinones
Mupirocin
91
Q

What agents are in the class of Aminoglycosides?

A

Gentamicin

Amikacin

92
Q

What is the mechanism of action of Aminoglycosides?

A

Binds 30S ribosomal subunit, causes subunit to misread genetic code

93
Q

What are the mechanisms of resistance of Aminoglycosides?

A
  • Decreased uptake of drug (chromosomally mediated)
  • Altered receptor on 30S with lower affinity for drug
  • Synthesis of enzymes that modify and inactivate aminoglycosides (chromosomally mediated)
94
Q

What are the common adverse events of Aminoglycosides?

A
  • Narrow therapeutic range (must monitor levels)
  • Ototoxicity (irreversible)
    • Cochlear damage: hearing loss
    • Vestibular damage: vertigo
  • Nephrotoxicity (do not give to renal insufficient patients)
  • Neuromuscular blockade
    • Do not give to myasthenia gravis patients!
  • Can cross placenta, do not give to pregnant patients
95
Q

What is the spectrum of activity of Aminoglycosides?

A

Gram neg (including Pseudomonas)
Also covers Mycobacteria, Francisella (Tularemia), Yersinia (Plague
NO Gram pos (but can see synergy when used with B-lactams since allows drug to penetrate cell wall)

96
Q

What are the clinical uses of Aminoglycosides?

A

Complicated UTIs
Used in combination with B-lactams for serious Gram-neg infections like bacteremia/sepsis
First line treatment for tularemia and plague

97
Q

What agents are in the class of Tetracyclines?

A

Doxycycline
Tetracycline
Minocycline

98
Q

What is the mechanism of action of Tetracyclines?

A

Binds 30S subunit, blocking access of tRNA to mRNA-ribosome complex

99
Q

What are the mechanisms of resistance of Tetracyclines?

A

Widespread resistance, limits clinical utility
- Gene transfer on plasmids
These genes encode proteins for active efflux and ribosomal protective proteins (RPPs)

100
Q

What are common adverse events associated with tetracyclines?

A
  • Permanent discoloration and hypoplasia of teeth
  • Stunted growth in children, do not give
  • Can cross placenta, do not give
  • Photosensitivity of skin
101
Q

What is the spectrum of activity of tetracyclines?

A

Broad spectrum, but limited by widespread resistance

  • Some Gram neg, usually CA, but limited due to resistance
  • Gram pos: Staph (includes some CA-MRSA) and Strep
  • Atypicals: Chlamydia, Mycoplasma
  • Spirochetes
102
Q

What are clinical uses of tetracyclines?

A
  • Bronchitis, CA-pneumonia
  • STIs: Chlamydia
  • Lyme disease
  • Doxycycline: Malaria prophylaxis
  • Minocycline - Acne treatment
103
Q

What agents are in class of Glycyclines?

A

Tigecycline

104
Q

What is the mechanism of action of glycyclines?

A

Bind 30S ribosomal subunit, inhibits protein translation and synthesis

105
Q

What are the mechanisms of resistance of Glycyclines?

A

Overcomes all tetracycline resistance with structural modifications

106
Q

What are the common adverse events associated with Glycyclines?

A

Same as tetracyclines

Discoloration of teeth, stunted growth in children, photosensitivity of skin

107
Q

What is the spectrum of activity of glycyclines?

A 
Gram neg (except Pseudomonas, Proteus, Morganella, Providencia)
Gram pos (including MRSA and VRE)
Anaerobes
108
Q

What are clinical uses of glycyclines?

A

Complicated skin and soft tissue infections
Complicated intra-abdominal infections
CA pneumonia

109
Q

What agents are in the class of Macrolides?

A

Azithromycin
Erythromycin
Clarithromycin

110
Q

What is the mechanism of action of the macrolides?

A

Binds 50S ribosomal subunit

111
Q

What are the mechanisms of resistance of macrolides?

A
  • Efflux pumps
  • Target site alteration: erm genes
    • Important for erythromycin and may infer clindamycin resistance
  • Decreased cell wall permeability (intrinsic resistance to some Gram neg)
112
Q

What are common adverse events of Macrolides?

A 
GI distress (common)
Prolonged QT interval
113
Q

What is the spectrum of activity of Macrolides?

A

Gram neg: most CA Gram neg, including Haemophilus influenza, Moraxella, E.Coli
Gram pos: Staph and Strep
Anaerobes: some Gram neg anaerobes
Atypicals: Chalmydia, Mycoplasma, Legionella

114
Q

What are clinical uses of Azithromycin?

A 
CA pneumonia and pronchities
Atypical pneumonia
STIs: Chlamydia
Traveler's diarrhea
Prophylaxis against Mycobacterium avium in HIV/AIDS patients
115
Q

What are the clinical uses of Erythromycin?

A

Infrequent use due to adverse effects

Sometimes for gut motility

116
Q

What are the clinical uses of Clarithromycin?

A

Used in combination with other agents to treat Helicobacter pylori or Mycobacterium avium

117
Q

What agents fall in class of Lincosamides?

A

Clindamycin

118
Q

What is the mechanism of action of Clindamycin?

A

Binds 50S ribosomal subunit

119
Q

What are the mechanisms of resistance of Clindamycin?

A
  • Erm gene mutation
    If S. aureus is susceptible to clindamycin and resistant to erythromycin, suspect it will get inducible clindamycin resistance
120
Q

What are common adverse events of clindamycin?

A

C. diff infection

Rare: hepatotoxicity, agranulocytosis

121
Q

What is the spectrum of activity of clindamycin?

A

NO Gram neg
Gram pos: Staph (including CA-MRSA) and Strep
Anaerobes: oral anaerobes, “above the diaphragm”
Parasites: malaria, toxoplasmosis

122
Q

What are clinical uses of Clindamycin?

A

CA-pneumonia
Oral/ENT infections, including abscesses “above the diaphragm”
Human bite wounds

123
Q

What agents are in the class of Oxazolidinones?

A

Linezolid, Tedizolid

124
Q

What is the mechanism of action of Oxazolidinones?

A

Bind 50S subunit and prevent formation of 70S initiation complex

125
Q

What are the mechanisms of resistance of Oxazolidinones?

A

Resistance is uncommon

  • Point mutations at target sites
  • Plasma mediated resistance gene cfr
126
Q

What are the common adverse events associated with Oxazolidinones?

A

Bone marrow suppression
Inhibits monoamine oxidase activity –> serotonin syndrome
Lactic acidosis with prolonged use

127
Q

What is the spectrum of activity of Oxazolidinones?

A

Gram pos ONLY (including MRSA and VRE)

NO Gram neg

128
Q

What are the clinical uses of Oxazolidinones?

A

VRE infections
Nosomicomial pneumonia due to MRSA
Complicated skin and soft tissue infections

129
Q

What is the mechanism of activity of Mupirocin?

A

Binds reversibly to isoleucyl tRNA synthetase, causing arrest in protein synthesis

130
Q

What is the spectrum of activity of Mupirocin?

A

Gram pos ONLY (but no enterococci)
NO Gram neg
NO anaerobic
Weaker activity against “normal skin flora”, good because keeps this natural defense

131
Q

What are clinical uses of Mupirocin?

A

Uncomplicated skin and soft tissue infections cause by Gram-pos
MRSA decoloniztion of anterior nares

132
Q

What agents are DNA synthesis inhibitors?

A

Class of Imidazoles
Includes:
- Metronidazole
- Tinidazole

133
Q

What is the mechanism of action of Imidazoles?

A

Production of free radicals

134
Q

What are common adverse events of Imidazoles?

A

Metallic taste
Neurologic effects from hyaluronic acid, vertigo, confusion
Disulfram-like effect when taken with alcohol leads to vomiting, flushing

135
Q

What is the spectrum of activity of Imidazoles?

A

ONLY anaerobes and protozoa

  • Gram neg anaerobes
  • C diff
  • “Below the diaphragm”
136
Q

What are the clinical uses of Imidazoles?

A

Anaerobic infections “below the diaphragm”
C. diff infection
Trichomonas and bacterial vaginosis

Bacteriology (19 decks)

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