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Antimicrobials Flashcards

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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
What are the common adverse events of Penicillins?
``` Hypersensitivity reactions (rashes, serum sickness) At high concentrations: seizures ```
26
What are the classes of Penicillins?
Penicillin G (and V) Semi-synthetic penicillins Aminopenicillins "Antipseudomonal" penicillins
27
What is the spectrum of activity of Penicillin G?
Gram positive cocci and anaerobes Gram negative cocci Spirochetes (syphilis)
28
What are the clinical uses of Penicillin G?
Infections caused by most Streptococci (if susceptible) Gram positive anaerobic infections (dental abscesses, bites) Syphilis
29
What agents are in the class of semi-synthetic penicillins and are they IV or PO?
Nafcillin - IV | Dicloxacillin - PO
30
What is the spectrum of activity of semi-synthetic penicillins?
NO Gram negatives | ONLY Gram positive cocci and anaerobes
31
What are the clinical uses of semi-synthetic penicillins?
Infections due to methicillin-SUSCEPTIBLE S. aureus (MSSA)
32
What agents fall in the class of aminopenicillins and are they IV or PO?
Ampicillin - IV | Amoxicillin - PO
33
What is the spectrum of activity of aminopenicillins?
Gram positive cocci and anaerobes | Some Gram neg bacilli
34
What are the clinical uses of aminopenicillins?
Community-acquired HEENT and upper respiratory infections | Community-acquired UTIs
35
What agents fall in the class of "antipseudomonal" penicillins?
Piperacillin
36
What is the spectrum of activity of Piperacillin?
Includes highly-resistant Gram-neg bacilli like Pseudomonas
37
What are the clinical uses of Piperacillin?
NONE ON ITS OWN. Only used in combination with tazobactam as a beta-lactamase inhibitor
38
What is the mechanism of action of beta-lactamase inhibitors?
Bind and hydrolyze beta-lactamases while beta-lactams remain intact and exert effect
39
What agents fall under the class of beta-lactamase inhibitors?
Ampicillin-sulbactam Amoxicillin-clavulanic Piperacillin-tazobactam
40
What is the spectrum of activity of beta-lactamase inhibitors?
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!
41
What are the clinical uses of beta-lactamase inhibitors?
Polymicrobial infections or resistant infections
42
What is the mechanism of action of cephalosporins?
Beta-lactam
43
How do beta-lactam agents work?
Covalently bind transpeptidases involved in forming the peptide cross-links in the peptidoglycan, creating a weakened cell wall. Autolysins will lyse cell.
44
What are the first generation cephalosporins?
Cefazolin | Cephalexin
45
What are the common adverse events of cephalosporins?
Minimal side effects Hypersensitivity Possible cross-reactivity with penicillin allergy
46
What is the spectrum of activity of first generation cephalosporins?
Gram positive Strep and Staph | Some Gram negative bacilli
47
What are the clinical uses of first generation cephalosporins?
Cefazolin - antimicrobial prophylaxis during surgery | Cephalexin - oral cephalosporin, usually skin and soft tissue infections from Strep and Staph (not MRSA)
48
What are the second generation cephalosporins?
Cefoxitin
49
What is the spectrum of activity of second generation cephalosporins?
Gram pos Strep and Staph Excellent activity against Gram neg anaerobes Increased activity against Gram neg bacilli
50
What are the clinical uses of second generation cephalosporins?
Treat intraabdominal infections or prophylaxis in intraabdominal surgery
51
What are the third generation cephalosporins?
Ceftriaxone, Ceftrazidime
52
What is the spectrum of activity of third generation cephalosporins?
Gram-pos Strep and Staph | Excellent activity against Gram neg cocci and bacilli (high degree of penetration into CSF)
53
What are the clinical uses of third generation cephalosporins?
Cefriaxone - meningitis, endocarditis and osteomyelitis, community-acquired pneumonia Ceftazidime - covers Pseudomonas!
54
What are the mechanisms of resistance to cephalosporins?
More resistant to beta-lactamases (not much effect) Intrinsic resistance (mostly enterococci and Pseudomonas) Altered membrane permeability - Pseudomonas Altered PBPs
55
What are the fourth generation cephalosporins?
Cefepime
56
What is the spectrum of activity of fourth generation cephalosporins?
Broadest spectrum Gram-positive Staph and Strep Extremely active against Gram neg bacteria including Pseudomonas
57
What are the clinical uses of fourth generation cephalosporins?
Pseudomonas
58
What are the fifth generation cephalosporins?
Ceftaroline
59
What is the spectrum of activity of ceftaroline?
Most Gram-pos (including MRSA but not enterococci) | Some Gram-neg (but not Pseudomonas)
60
What are the clinical uses of ceftaroline?
MRSA treatment
61
What agents are in the class of Carbapenems?
Imipenem | Ertapenem
62
What is the mechanism of action of Carbapenems?
Beta-lactam
63
What are the mechanism of resistance of Carbapenems?
Not much resistance Resistance to most beta-lactamases Some carbapenemases exist
64
What are common adverse side effects of Carbapenems?
Hypersensitivity reactions Seizures at high concentration Possible cross-reactivity with penicillin allergy
65
What is the spectrum of activity of Carbapenems?
Very broad Gram pos (including Enterococcus faecalis) Gram neg (including Pseudomonas, except when treating with Ertapenem) Anaerobes
66
What are the clinical uses of carbapenems?
Serious infections | Treatment of infections due to resistant bacteria
67
What agents are in the class of Monobactams?
Aztreonam
68
What is the mechanism of action of aztreonam?
Beta-lactam
69
What are the common adverse side effects of aztreonam?
Little cross-reactivity to penicillin or cephalosporin allergy
70
What is the spectrum of activity of aztreonam?
Gram negative ONLY | No Gram positive
71
What are the clinical uses of aztreonam?
Used as alternative for patients with penicillin/cephalosporin allergy
72
What are the agents in the category of glycopeptides?
Vancomycin
73
What is the mechanism of action of vancomycin?
Binds terminal D-alanine dipeptide of peptidoglycan, inhibits glycosyltransferase and transpeptidase
74
What are mechanism of resistance of vancomycin?
Alteration of vancomycin binding site (encoded by vanA - vanE) Thickened cell wall resulting in inability of antibiotic to penetrate
75
What are common adverse side effects of vancomycin?
"Red Man" syndrome: flushing, redness, hypotension during infusion Dose related ototoxicity Nephrotoxicity (must monitor levels)
76
What is the spectrum of activity of vancomycin?
Gram positive ONLY (including MRSA) | NO Gram negative
77
What are clinical uses of vancomycin?
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
What agents are in the class of cyclic lipopeptides?
Daptomycin
79
What is the mechanism of action of daptomycin?
Inserts lipophilic tail into cell membrane --> rapid membrane depolarization and efflux of K+
80
What are the common adverse side effects of daptomycin?
GI upset, rash, headache Elevation of creatine phosphokinase (CPK) and possible rhabdomyolysis associated with higher dosing - Should monitor CPK levels
81
What is the spectrum of activity of daptomycin?
Gram pos (includes MRSA and VRE) Gram pos anaerobes NO Gram neg activity
82
What are the clinical uses of daptomycin?
Complicated skin and soft tissue infections, bacteremia, endocarditis
83
What is the mechanism of action of polymixins?
Bind LPS and disrupt outer membrane
84
What are common adverse effects of polymixins?
Significant toxicities (nephrotoxicity, neurotoxicity, bronchospasm)
85
What is the spectrum of activity of polymixins?
ONLY Gram neg bacilli | Reemerged in usage despite toxicity due to strains of Acinetobacter and Pseudomonas resistant to all other agents
86
What are the clinical uses of polymixins?
Serious resistant Gram neg infections, pneumonia
87
What is the spectrum of activity of Bacitracin?
Gram pos ONLY
88
What are the clinical uses of Bacitracin?
Ointments (topical), often in combination with other antimicrobials
89
What are the clinical uses of Fosfomycin?
UTI only (in an oral powder)
90
What antimicrobials fall under the classification of Protein Synthesis Inhibitors?
``` Aminoglycosides Tetracyclines Glycyclines Macrolides Lincosamides Oxazolidinones Mupirocin ```
91
What agents are in the class of Aminoglycosides?
Gentamicin | Amikacin
92
What is the mechanism of action of Aminoglycosides?
Binds 30S ribosomal subunit, causes subunit to misread genetic code
93
What are the mechanisms of resistance of Aminoglycosides?
- 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
What are the common adverse events of Aminoglycosides?
- 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
What is the spectrum of activity of Aminoglycosides?
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
What are the clinical uses of Aminoglycosides?
Complicated UTIs Used in combination with B-lactams for serious Gram-neg infections like bacteremia/sepsis First line treatment for tularemia and plague
97
What agents are in the class of Tetracyclines?
Doxycycline Tetracycline Minocycline
98
What is the mechanism of action of Tetracyclines?
Binds 30S subunit, blocking access of tRNA to mRNA-ribosome complex
99
What are the mechanisms of resistance of Tetracyclines?
Widespread resistance, limits clinical utility - Gene transfer on plasmids These genes encode proteins for active efflux and ribosomal protective proteins (RPPs)
100
What are common adverse events associated with tetracyclines?
- Permanent discoloration and hypoplasia of teeth - Stunted growth in children, do not give - Can cross placenta, do not give - Photosensitivity of skin
101
What is the spectrum of activity of tetracyclines?
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
What are clinical uses of tetracyclines?
- Bronchitis, CA-pneumonia - STIs: Chlamydia - Lyme disease - Doxycycline: Malaria prophylaxis - Minocycline - Acne treatment
103
What agents are in class of Glycyclines?
Tigecycline
104
What is the mechanism of action of glycyclines?
Bind 30S ribosomal subunit, inhibits protein translation and synthesis
105
What are the mechanisms of resistance of Glycyclines?
Overcomes all tetracycline resistance with structural modifications
106
What are the common adverse events associated with Glycyclines?
Same as tetracyclines | Discoloration of teeth, stunted growth in children, photosensitivity of skin
107
What is the spectrum of activity of glycyclines?
``` Gram neg (except Pseudomonas, Proteus, Morganella, Providencia) Gram pos (including MRSA and VRE) Anaerobes ```
108
What are clinical uses of glycyclines?
Complicated skin and soft tissue infections Complicated intra-abdominal infections CA pneumonia
109
What agents are in the class of Macrolides?
Azithromycin Erythromycin Clarithromycin
110
What is the mechanism of action of the macrolides?
Binds 50S ribosomal subunit
111
What are the mechanisms of resistance of macrolides?
- 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
What are common adverse events of Macrolides?
``` GI distress (common) Prolonged QT interval ```
113
What is the spectrum of activity of Macrolides?
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
What are clinical uses of Azithromycin?
``` CA pneumonia and pronchities Atypical pneumonia STIs: Chlamydia Traveler's diarrhea Prophylaxis against Mycobacterium avium in HIV/AIDS patients ```
115
What are the clinical uses of Erythromycin?
Infrequent use due to adverse effects | Sometimes for gut motility
116
What are the clinical uses of Clarithromycin?
Used in combination with other agents to treat Helicobacter pylori or Mycobacterium avium
117
What agents fall in class of Lincosamides?
Clindamycin
118
What is the mechanism of action of Clindamycin?
Binds 50S ribosomal subunit
119
What are the mechanisms of resistance of Clindamycin?
- Erm gene mutation If S. aureus is susceptible to clindamycin and resistant to erythromycin, suspect it will get inducible clindamycin resistance
120
What are common adverse events of clindamycin?
C. diff infection | Rare: hepatotoxicity, agranulocytosis
121
What is the spectrum of activity of clindamycin?
NO Gram neg Gram pos: Staph (including CA-MRSA) and Strep Anaerobes: oral anaerobes, "above the diaphragm" Parasites: malaria, toxoplasmosis
122
What are clinical uses of Clindamycin?
CA-pneumonia Oral/ENT infections, including abscesses "above the diaphragm" Human bite wounds
123
What agents are in the class of Oxazolidinones?
Linezolid, Tedizolid
124
What is the mechanism of action of Oxazolidinones?
Bind 50S subunit and prevent formation of 70S initiation complex
125
What are the mechanisms of resistance of Oxazolidinones?
Resistance is uncommon - Point mutations at target sites - Plasma mediated resistance gene cfr
126
What are the common adverse events associated with Oxazolidinones?
Bone marrow suppression Inhibits monoamine oxidase activity --> serotonin syndrome Lactic acidosis with prolonged use
127
What is the spectrum of activity of Oxazolidinones?
Gram pos ONLY (including MRSA and VRE) | NO Gram neg
128
What are the clinical uses of Oxazolidinones?
VRE infections Nosomicomial pneumonia due to MRSA Complicated skin and soft tissue infections
129
What is the mechanism of activity of Mupirocin?
Binds reversibly to isoleucyl tRNA synthetase, causing arrest in protein synthesis
130
What is the spectrum of activity of Mupirocin?
Gram pos ONLY (but no enterococci) NO Gram neg NO anaerobic Weaker activity against "normal skin flora", good because keeps this natural defense
131
What are clinical uses of Mupirocin?
Uncomplicated skin and soft tissue infections cause by Gram-pos MRSA decoloniztion of anterior nares
132
What agents are DNA synthesis inhibitors?
Class of Imidazoles Includes: - Metronidazole - Tinidazole
133
What is the mechanism of action of Imidazoles?
Production of free radicals
134
What are common adverse events of Imidazoles?
Metallic taste Neurologic effects from hyaluronic acid, vertigo, confusion Disulfram-like effect when taken with alcohol leads to vomiting, flushing
135
What is the spectrum of activity of Imidazoles?
ONLY anaerobes and protozoa - Gram neg anaerobes - C diff - "Below the diaphragm"
136
What are the clinical uses of Imidazoles?
Anaerobic infections "below the diaphragm" C. diff infection Trichomonas and bacterial vaginosis

Bacteriology (19 decks)

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