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Infectious Agents > Exam 1: Antimicrobial Resistance > Flashcards

Exam 1: Antimicrobial Resistance Flashcards

1
Q

What is minimum inhibitory concentration?

A

The lowest concentration of a drug that will completely inhibit growth of a bacterial strain

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2
Q

When is a bacterial strain resistance to an antibiotic?

A

When its MIC is higher than the normally achievable and tolerated concentration of the drug attained in tissues with maximum dosage

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3
Q

How do antibiotics act?

A

By inactivating a specific bacterial target

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4
Q

What are mechanisms of antibiotic resistance?

A

Modification of the antibiotic target
Enzymatic inactivation of the antibiotic
Impermeability
Active efflux

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5
Q

What do beta-lactams (penicillins and cephalosporins) do?

A

Alteration of the target protein (penicillin-binding protein) so that the antibiotic no longer binds it

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6
Q

What are penicillin-binding proteins?

A

Bacterial enzymes that mediate crosslinking of peptidoglycan in formation of the cell wall

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7
Q

What is the modification of the target antibiotic resistance a common mechanism of?

A

Causing gram-positive bacterial beta-lactam resistance

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8
Q

What is an example of enzymatic inactivation of the antibiotic?

A

Beta-lactamase

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9
Q

What are beta-lactamases?

A

Bacterial enzyme that cleaves the beta-lactam ring

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10
Q

Where is beta-lactamase secreted by gram-negative?

A

Periplasmic space

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11
Q

Where is beta-lactamase secreted by gram-positive?

A

Into extracellular fluid

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12
Q

What are beta-lactamases usually active against?

A

A subset of beta-lactam antibodies

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13
Q

What can beta-lactamase inhibitors (clavulanic acid) do?

A

Prevent inactivation by beta-lactamases

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14
Q

What does the gram-negative outer membrane do in impermeability?

A

Limits antibiotic access to the cytoplasmic membrane because antibiotics must first diffuse through pores in outer membrane

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15
Q

What is impermeability thought to be the reason for?

A

E. coli innate resistance to macrolides

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16
Q

What do mutations in porins do to impermeability?

A

Limit diffusion of antibiotics

A single porin mutation can confer resistance to more than one antibiotic type

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17
Q

What is an example of active efflux?

A

Tetracycline

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18
Q

What is tetracycline?

A

Bacterial cytoplasmic membrane proteins that catalyze energy-dependent transport of tetracycline out of the cytoplasm

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19
Q

What does active efflux do?

A

Prevents sufficient antibiotic concentrations in the cytoplasm to inhibit protein synthesis

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20
Q

What does the active efflux system also exist for?

A

Quinolones

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21
Q

How does antibiotic resistance arise?

A

Genetic mechanisms
Phenotypic variants
Biofilms

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22
Q

What are the genetic mechanisms of antibiotic resistance?

A

Genetic resistance is likely to be detected by susceptibility testing; therefore, it is usually detected at the onset of therapy
Unlikely to appear during a course of antibiotic therapy

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23
Q

What are the 2 mechanisms that genetic resistance can arise?

A

Gaining the ability to resist one or more antibiotics by acquisition of genes
Resistance from random mutations

24
Q

What are antibiotic resistance genes usually acquired on?

A

Plasmids

25
Q

What do almost all antibacterial drugs have?

A

A corresponding resistance gene on at least one type of R plasmid

26
Q

What do resistance (R) plasmids do?

A

Mediate resistance to more than one antibiotic

27
Q

What can plasmids carry?

A

Transposons

28
Q

What does gene acquisition typically result in?

A

Rapid acquisition of high-level resistance

29
Q

What enzymatic antibiotic inactivation and active efflux require for the function to acquired?

A

The acquisition of a gene

30
Q

What can the altered antibiotic target strategy occur by?

A

Acquisition of a gene encoding an altered target

31
Q

What type of mutation are the random mutations typically?

A

Point mutations (change of one base pair into another)

32
Q

What can random mutations do?

A

Revert back to the original gene sequence

33
Q

What can a single base pair change result in?

A

High level resistance, but often multiple mutations have to be acquired so development of resistance can be gradual

34
Q

How can random mutations result in resistance?

A

By either reducing permeability or altering target affinity

35
Q

What can random mutations do in addition to causing antibiotic resistance?

A

They can be deleterious and cause some degree of growth impairment, and in some cases cause reduction in virulence (fitness cost)

36
Q

What is fitness cost?

A

Often the mutation causing resistance also has a cost due to decreased function of the altered target

37
Q

What do random mutations carry more than horizontal gene transfer?

A

Fitness cost

38
Q

What mechanisms of antibiotic resistance does gene acquisition act by?

A

Alteration of target
Inactivation of antibiotic
Active efflux

39
Q

What mechanisms of antibiotic resistance does random mutation act by?

A

Alteration of target

Impermeability

40
Q

Why can phenotypic variants not be detected on antibiotic sensitivity testing?

A

It is not genetic

41
Q

What are the types of phenotypic variants?

A

Bacterial persisters
Small colony variants
L-forms

42
Q

What are bacterial persisters?

A

Non- or slow-growing reversible phenotypic variants of the wild type, tolerant to bactericidal antibiotics

43
Q

What is persister tolerance of antibiotics due to?

A

Inhibition of essential cell functions during antibiotic stress, resulting in inactivity of the antibiotic target

44
Q

What does persistence require?

A

Coordinated metabolic changes

45
Q

What is entry and exit from the persister state regulated by?

A

Signal molecules

46
Q

What do small colony variants have?

A

Reduced electron transport, which leads to decreased ATP syntheesis

47
Q

What is the cause of reduced electron transport in small colony variants?

A

Reduced hemin or menadione biosynthesis or defective thymine deficiency

48
Q

What is the result of reduced electron transport in small colony variants?

A

Decreased metabolism and decreased uptake of antibiotic, causing temporary antibiotic resistance

49
Q

When do L-forms occur?

A

When bacteria lose their cell wall

They are temporarily more resistance to beta-lactam antibiotics

50
Q

Where are L-forms found?

A

Historically in gram-negative, but recently found in listeria and mycobacterium

51
Q

When do L-forms work?

A

When bacteria are in an environment where they are not susceptible to osmotic lysis

52
Q

What is biofilm?

A

A structure community of bacteria enclosed in a self-produced polymeric matrix and adherent to an inert or living surface

53
Q

What can bacteria in a biofilm do?

A

Convert into a regular planktonic state

54
Q

What is resistance due to in biofilm?

A

Slower growth rates of bacteria within biofilms
Decreased diffusion of antibiotics through the biofilm
Accumulation of enzymes that contribute to resistance
Activation of stress response in bacteria in biofilms

55
Q

Where can biofilms be found?

A

Indwelling catheters

Infectious Agents (38 decks)

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