VM519: Cutaneous System > Antibiotics > Flashcards

Antibiotics Flashcards

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1
Q

What is the mechanism of action of beta-lactam antibiotics (penicillins, cephalosporins, carbapenems)?

A

They bind to penicillin-binding proteins (PBPs), inhibiting cross-linking of peptidoglycan in the bacterial cell wall.

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2
Q

What bacteria species has One Health implications for both Animal and Humans?

A

Staphylococcus aureus

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3
Q

What is the mechanism of action of bacitracin?

A

It interferes with C55-isoprenyl pyrophosphate and bactoprenol pyrophosphate, which transport peptidoglycan precursors across the inner bacterial membrane.

Targets cell wall!!!

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4
Q

What is the mechanism of action of polymyxin B?

A

It binds lipopolysaccharide (LPS) in gram-negative outer membranes and disrupts outer and inner plasma membranes.

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5
Q

What causes a resistance to Polymyxin?

A

Mutation of mcr-1, which modifies structure of LPS and prevents binding.

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6
Q

What is the mechanism of action of trimethoprim-sulfa (TMS)?

A

Sulfamethoxazole competes with PABA to bind to dihydropteroate synthetase.

Trimethoprim - competitive inhibition of dihydrofolate reductase (DHFR)

Together they block folate synthesis, preventing DNA and protein synthesis.

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7
Q

What antibiotic targets the folate pathway?

A

Trimethoprim/sulfa (TMS)

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8
Q

What is the mechanism of action of fluoroquinolones (enrofloxacin, marbofloxacin, pradofloxacin, ciprofloxacin)?

A

Gram-negative: inhibit DNA gyrase.

Gram-positive: inhibit topoisomerase IV.

Both actions prevent DNA replication.

Intracellular pathogens!

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9
Q

What antibiotic targets DNA gyrase?

A

Fluoroquinolones

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10
Q

Four examples of (fluoro)quinalones?

A
  • Enrofloxacin (Baytril)
  • Marbofloxacin (Zeniquin)
  • Pradofloxacin (Veraflox)
  • Ciprofloxacin
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11
Q

What is the mechanism of action of rifampin?

A

It inhibits bacterial DNA-dependent RNA polymerase = DNA-dependent RNA synthesis cannot occur.

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12
Q

What is the mechanism of action of macrolides (erythromycin, clarithromycin, azithromycin)?

A

They target peptidyl transferase of the 50S ribosomal subunit, causing premature detachment of incomplete peptide chains.

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13
Q

Three examples of Macrolides

A
  • Erythromycin
  • Clarithromycin
  • Azithromycin
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14
Q

Example of Lincosamides

A

Clindamycin

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15
Q

Lincosamide resistance also involves ______ pumps.

A

Efflux pumps - resistance nodulation cell division superfamily

Less likely to occur with Staphylococcus spp.

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16
Q

What cells are Lincosamides concentrated in before they are transported to the site of infection?

A

Leukocytes

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17
Q

What gram of bacteria are Lincosamides useful for?

A

Gram-POSITIVE (unable to pass thru gram-negative porins)

Avoid in hindgut fermenters! (horses, rabbits)

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18
Q

What class of antibiotics target the 50S ribosomal subunit?

A
  • Macrolides
  • Lincosamides
  • Chloramphenicol (and Florfenicol)
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19
Q

What is the mechanism of action of lincosamides (clindamycin)?

A

Same as macrolides: inhibition of peptidyl transferase in the 50S ribosomal subunit, causing premature detachment of incomplete peptides.

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20
Q

What is the mechanism of action of chloramphenicol and florfenicol?

A

They inhibit peptidyl transferase in the 50S ribosomal subunit, preventing elongation of the protein chain.

Pretty much same as Macrolides and Lincosamides! All three affect 50S ribosomal subunit.

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21
Q

What is the mechanism of action of tetracyclines (tetracycline, oxytetracycline, doxycycline, minocycline)?

A

They bind to the 30S ribosomal subunit and prevent tRNA from binding to the ribosome.

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22
Q

What are two subgroup antibiotics that target the 30S ribosomal subunit?

A
  • Tetracyclines
  • Aminoglycosides
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23
Q

Four examples of Aminoglycosides

A
  • Neomycin (bovine, ruminant, swine, poultry)
  • Gentamicin (horse, swine, poultry)
  • Amikacin (dogs, horses)
  • Tobramycin

Both Topical and Systemic are FDA approved.

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24
Q

What is the mechanism of action of aminoglycosides (neomycin, gentamicin, amikacin, tobramycin)?

A

They bind the 30S ribosomal subunit and prevent peptide elongation.

Also impair translational proofreading, causing abnormal proteins to insert into the bacterial membrane.

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25
Which microbes are most susceptible to beta-lactams (penicillins, cephalosporins, carbapenems)?
Gram-positive bacteria, because their thick peptidoglycan cell wall is the primary target.
26
Which microbes require potentiated penicillins (e.g., amoxicillin-clavulanate) due to penicillinase production?
Most Staphylococcus spp., especially skin Staphylococci.
27
Why can plain penicillins NOT be used for Staphylococcus infections?
Staphylococci produce penicillinase (a beta-lactamase), which breaks open the beta-lactam ring.
28
Which microbes are most susceptible to bacitracin?
Gram-positive bacteria such as Staphylococcus spp. and Streptococcus spp.
29
Which microbes are most susceptible to polymyxin B?
Gram-negative bacteria, because polymyxin binds LPS in the outer membrane. ## Footnote Usually topical use!!!
30
What antibiotic targets the bacterial plasma membrane?
Polymyxin
31
Which microbes are commonly treated with trimethoprim-sulfa (TMS)?
Staphylococcal skin infections and urinary tract infections.
32
What antibiotics target nucleic acid synthesis?
* Trimethoprim + Sulfa (TMS) * Rifampin * (Fluoro)quinolones
33
Which microbes are susceptible to fluoroquinolones (enrofloxacin, marbofloxacin, pradofloxacin)?
Very broad spectrum: gram-positive, gram-negative, and intracellular pathogens.
34
Which microbes develop fluoroquinolone resistance rapidly?
Pseudomonas spp. (efflux pumps, plasmid genes, and gyrase mutations).
35
Which microbes are treated with rifampin?
* Rhodococcus equi in foals (with macrolide) * Resistant Staphylococcus spp. * Also mycobacterial infections.
36
Macrolides concentrate in what cells?
Concentrates in leukocytes, then transported to site of infection.
37
What gram of bacteria are Macrolides useful for?
**Gram-POSITIVE** * Limited gram-negative (Bordetella) ## Footnote Anti-inflammatory effects!
38
What subgroup of drug is **combined with rifampin** to treat **Rhodococcus equi pneumonia in foals**?
Macrolides ## Footnote AVOID IN HINDGUT FERMENTERS!!!!!!! (horses, rabbits) - okay in foals <1 year old.
39
How many kinds of RNA polymerase in prokaryotes?
Only one kind. ## Footnote Critical for gene expression!
40
What antibiotic targets DNA-directed RNA polymerase?
Rifampin
41
Which microbes are most susceptible to macrolides (erythromycin, azithromycin, clarithromycin)?
Gram-positive bacteria; limited gram-negative activity (e.g., Bordetella).
42
Which microbes are most susceptible to lincosamides (clindamycin)?
Gram-positive bacteria; cannot pass through gram-negative porins.
43
Which microbes are susceptible to chloramphenicol/florfenicol?
Broad spectrum: Staphylococcus spp., Streptococcus spp., E. coli — **NOT effective against Pseudomonas aeruginosa.**
44
Which microbes are susceptible to tetracyclines (tetracycline, doxycycline, oxytetracycline)?
Broad spectrum, including Rickettsial organisms (e.g., Lyme, Ehrlichia).
45
Tetracyclines have anti-inflammatory and/or ________ effects.
immunomodulatory ## Footnote Works for some autoimmune diseases, but this use is controversial.
46
__________ inhibit matrix matalloproteases.
Tetracyclines
47
Four examples of Tetracyclines
* Tetracycline * Oxytetracycline * Doxycycline * Minocycline
48
Tetracyclines: mechanism of action
Binds to 30S ribosomal subunit and **prevents tRNA from binding** to ribosome. ## Footnote * Diffuse into bacteria through porins * Would have same effect on eukaryotic cells, except we lack porins
49
What causes resistance to Tetracyclines?
Energy-dependent efflux
50
Which microbes are most susceptible to aminoglycosides (neomycin, gentamicin, amikacin)?
Gram-negative aerobes.
51
What enzyme causes resistance to beta-lactam antibiotics?
Beta-lactamase, which breaks open the beta-lactam ring.
52
What is penicillinase, and which organisms commonly produce it?
A beta-lactamase specific for penicillins; produced by most Staphylococcus spp.
53
Why can plain penicillins not be used for Staphylococcal infections?
Staphylococci intrinsically produce penicillinase.
54
What is the purpose of adding clavulanate, sulbactam, or tazobactam to amoxicillin?
These compounds **inhibit beta-lactamase**, restoring beta-lactam activity (e.g., amoxicillin-clavulanate/Clavamox).
55
What gene causes methicillin resistance in Staphylococcus spp.?
The mecA gene.
56
What does the mecA gene encode?
PBP2A (penicillin-binding protein 2A).
57
Having the MecA gene confers resistance to ALL ______ antibiotics.
beta-lactam
58
How does Penicillin Binding Protein 2A (PBP2A) cause resistance?
It has low affinity for beta-lactams, preventing the drug from inhibiting cell wall synthesis.
59
What antimicrobials does mecA-mediated resistance affect?
ALL beta-lactams, including carbapenems and potentiated penicillins (e.g., Clavamox).
60
Which bacterial species develops fluoroquinolone resistance especially rapidly?
Pseudomonas spp.
61
What mechanisms lead to fluoroquinolone resistance?
* **Efflux pumps** - pump the drug out of bacterial cell, may confer **multi-drug resistance**, especially in Pseudomonas * Plasmid-mediated resistance genes - protein bind to DNA gyrase, preventing drug from binding * Mutations in DNA gyrase prevent binding.
62
What is intrinsically resistant to rifampin?
Some bacteria are naturally resistant, including Enterobacteriaceae, Acinetobacter spp., and **Pseudomonas spp.**
63
What causes induced resistance to rifampin?
Mutations in the rpoB gene, which encodes the beta-subunit of RNA polymerase.
64
How is Rifampin resistance induced?
Develops very readily during a single course. **Should always be given with a 2nd antibiotic to reduce the rapidity that resistance develops.**
65
Why must rifampin always be used with a second antibiotic?
Resistance develops readily during a single course of therapy.
66
What mechanism causes resistance to lincosamides and macrolides?
erm genes encode methyltransferases that demethylate the ribosomal subunit, preventing antibiotic binding.
67
What other mechanism can cause high-level resistance to macrolides/lincosamides?
Mutations of the transferase binding pocket in the ribosomal subunit.
68
What mechanism can cause resistance to aminoglycosides?
Mutations or decreased permeability that reduce drug uptake into bacterial cells.
69
What mechanism causes chloramphenicol resistance?
The CAT gene encodes chloramphenicol acetyltransferase, which inactivates the drug. Acetylates hydroxyl groups on chloramphenicol = can no longer bind to 50S ribosome. ## Footnote CONFERS HIGH-LEVEL RESISTANCE!
70
Reduced ______ permeability can also cause Chloramphenicol resistance.
membrane
71
What is the most common mechanism of low-level resistance?
Reduced membrane permeability!
72
What is a rare cause of resistance to Chloramphenicol?
Mutation of the 50S ribosomal subunit.
73
What three groups of antibiotics target the cell wall?
* Beta-lactams * Bacitracin * Vancomycin
74
What gram bacteria tends to be the most susceptible to antibiotics that target the cell wall?
Gram-POSITIVE
75
What are the three subgroups of Beta-lactams?
* Penicillins * Carbapenems * Cephalosporins
76
Four common Penicillins
* Penicillin * Amoxicillin * Ampicillin * Oxacillin/methicillin
77
Two common Carbapenems
* Meropenem * Imapenem
78
Five common Cephalosporins
* Cephalexin * Cefazolin * Ceftazidime * Cefpodoxime * Cefovecin
VM519: Cutaneous System
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