(05) Antibiotic Resistance Flashcards

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1
Q

Differentiate between acquired and innate drug resistance.

A

Innate:
- exists prior to the use of the drug

Acquired:
- selection and accumulation of resistant strains

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2
Q

Gram (-) bacteria is mostly resistant to ß-lactams. what type of resistance does this bacteria have?

A
  • Innate, most gram (-) and intracellular bacteria are ß-lactam resistant because of the barrier created by the cytoplasmic membrane
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3
Q

What are the 3 most common ways for a bacteria to acquire resistance to an antibiotic?
- which occur horizontally

A
  1. Chromosomal Mutations
  2. Transposons
  3. R-factor transfer

**R-factor much more likely to account for horizontal transfer than the other two

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4
Q

T or F: patients can only have infections that are multidrug resistant to drugs they’ve been treated with.

A

False, they can acquire MDR strains from other people

**NOTE: often the R-factor contains several MDR genes

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5
Q

5 basic tenants of antibiotic resistance

A
  1. It will emerge
  2. it will get more resistant
  3. likely to become resistant to other antibiotic
  4. They will persist
  5. use of antibiotics by one person affects other in extended and immediate healthcare environment
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6
Q

When would you use bactericidal antibiotics?

A

For:

  1. Potentially lethal infections
  2. Chronic infections
  3. Those involving Biofilms
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7
Q

When do you use bacteriostatic antibiotics?

A

When the immune system can be relied upon to assist in clearance.

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8
Q

What is the MIC?

A
  • Minimum inhibitory concentration

- Lowest bacterial concentration that inhibits growth

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9
Q

How do we test for MIC?

A
  • Kirby-Bauer method

- E Strip Test

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10
Q

How does E-strip test work?

  • how do you find MIC?
  • how do you find MBC (minimum bactericidal conc.)?
A

Stick contains serial dilutions

  • Point where bacteria touch the stick = MIC
  • MBC - bascially the same but might be a little bit more concentrated
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11
Q

T or F: antibiotic resistant bacteria is more virulent than other bacteria

A

False, just because its antibiotic resistant doesn’t mean its better at establishing infection
- in a world with no antibiotics the course of the infection would be the same

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12
Q

What is the reason for using multidrug therapy on bacteria?

A
  1. You double the unlikely hood of a favorable mutation conferring resistance
  2. Probably Synergy
  3. Likely Polymicrobial infection
  4. Uncertain Diagnosis
  5. Reduction of therapeutic levels of toxic drug
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13
Q

What are the 4 different mechanisms by which antibiotic resistance can be conferred?

A
  1. Exclusion
  2. Active Export
    - MDR pumps
  3. Target Alteration
  4. Drug inactivation
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14
Q

Exclusion

  • Gram (-) approach
  • Gram (+) approach
A

Gram (-)

  • remove porins from surface
  • remove transport system
  • Alteration of membrane lipids

Gram (+)
- increased cell wall thickness (traps vancomycin)

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15
Q

Multidrug-Resistance Efflux Pumps

  • what induces these?
  • class?
  • IMPORTANT FOR RES. TO WHAT DRUG?
A
  • Induced in presence of drug
  • ABC transporter
  • TETRACYCLINE
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16
Q

Altered Targets

- targets that are most often altered?

A
  • Ribosomes, topoisomerases, RNA polymerases, and TRANSPEPTIDASES (ignore ß-lacatams)
17
Q

How does MRSA work?

- what is it resistant to?

A
  • Resistant to ALL ß-lactams
  • Have aqcuired TRANSPOSON containing mecA gene
  • Encodes minor transpeptidase that works while the principle ones are being inhibited by ß-lacatams
18
Q

Why are newer drugs designed to binds multiple sites?

A
  • They prevent a Knockout alteration
19
Q

What are VRE and VRSA

- how are they antibiotic resistant?

A

Vancomycin Resistant:

  • Enterococci
  • Staphylococcus Aureus

PLASMID containing VanA gene encodes an enzyme that makes D-Ala D-Lactate (instead of D-Ala D-Ala)

  • Vancomycin can bind D-Ala D-lactate
20
Q

What happens of MRSA aquired VanA plasmid?

A

You’re screwed because Vancomycin is usually used for MRSA infections

21
Q

How does Chloramphenicol Resistance Arise?

A
  • Methylation of 50S subunit prevents Chloramphenicol from binding
22
Q

Why is antibiotic inactivation the most potent form of inactivation?
- 2 types of inactivation

A
  • It doesn’t require sacrifice on any working part of the bacteria

2 types:

  1. Modification
  2. Destruction
23
Q

Types of antibiotic inactivation through modification?

- what antibiotic is particularly susceptible to this?

A
  • Acetylation, Phophorylation, adenylation of OH or NH groups
  • Aminoglycosides are very susceptible

**Overall causes reduction of affinity for target

24
Q

Why antibiotic type undergoes inactivation by destruction?

  • enzyme responsible
  • how do we prevent this?
A

ß-lactams by ß-lactamases (1st. found in S. aureus)

  • Prevent by using Methicllin, Oxacillin or Cephalosporins that are bound by clavulanic acid
25
Q

Where are ß-lactamases found?

  • gram (+)
  • gram (-)
  • what modality does this resistance travel by?
A

Gram (+)
- secreted into immediate environment

Gram (-)
- Periplasmic space

*Travels via plasmid

26
Q

Why are ß-lactamases more significant in Gram (-) bacteria?

A
  • ß-lactamase gene is on a plasmid

- gram (-) bacteria are much more likely to exchange plasmids

27
Q

What are ESBLs?

  • what does they do?
  • Associated bacteria?
A

Extended Spectrum ß-lactamases

  • Can kill later generation drugs like cephalosporins

Associated with Gram (-) rods, including:

  • E. Coli
  • Klebsiella
  • Pseudomonas

*many of these are MDR

28
Q

What are 3 common types of ESBLs?

A
  1. TEMs
  2. SHVs
  3. CTX-M
29
Q

Carbapenemase

  • why is it worse than ESBL?
  • Associated bacteria?
A

Cleaves:

  • Carbapenems (alt. treatment for ESBL infects.)
  • Penicillins
  • Cephalosporins

Gram (-) rods:

  • Klebsiella pneumoniae cabapenemase (KPC)
  • NDM-1

**New MDR bacteria of hospitals

30
Q

what are CRE?

A

Carbapenemase-resistan Enterobacteriaceae

31
Q

MDR strains are often associated with…

A

Plasmid Transmission

32
Q

Why should you limit use of fluroquinolone when treating gram (-) enteric infections?

A

Because of Multidrug Resistance Plasmids that also contain ß-lacatamases and aminoglycoside resistant gener

33
Q

What are two primary factors that lead to antibiotic resistance?
- why?

A
  1. Overuse of antibiotics
  2. Antibiotic use for livestock
    - antibiotic resistant bacteria become a part of their normal flora
34
Q

What are the 5 keys to controlling antibiotic resistance?

A
  1. Developement of New Antibiotics
  2. Prudent use of existing antibiotics
  3. Development of more vaccines
  4. Better infection control in hosipitals
  5. Reduction of antibiotic use in the livestock industry