EXAM 2 Antibiotic Resistance Flashcards

1
Q

antibiotics are synthesized by ___ or ___

A

molds or bacteria

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2
Q

naturally occurring antibiotics can be chemically modified to ___

A

improve/alter their activities

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3
Q

in 1900 prior to antibiotics and vaccines, pneumonia, TB, diarrhea and enteritis, together with diphtheria caused ___ of all deaths

A

1/3

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4
Q

___ was discovered by alexander fleming in st. mary’s hospital in london, september 1928. it was rediscovered by howard florey ___ years later.

A
  • penicillin
  • 10
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5
Q

penicillin production was optimized in the US with the use of ___

A

new growth media and new molds

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6
Q

how many additional antibiotics have been developed since penicillin was introduced?

A

over 140

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7
Q

antibiotics save over ___ lives each year in the USA, adding ___ years to US life expectancy

A
  • 200k
  • 5-10
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8
Q

which antibiotics target cell wall synthesis/integrity?

A
  • beta lactams
  • glycopeptides
  • bacitracin
  • fosfomycin
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9
Q

which antibiotics target RNA synthesis?

A

rifampin

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10
Q

which antibiotic targets amino-acyl tRNA synthetase?

A

mupirocin

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11
Q

which antibiotics target folic acid (tetrahydrofolate) synthesis?

A

sulfonamides and trimethoprim

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12
Q

which antibiotics target protein synthesis via the 30S ribosome?

A

aminoglycosides and tetracyclines

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13
Q

which antibiotics target protein synthesis via the 50S ribosome?

A
  • chloramphenicol
  • macrolides
  • lincosamides
  • streptogramins
  • everninomycin
  • oxazolinonones
  • lincosamides
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14
Q

which antibiotics target DNA replication/repair/segregation?

A
  • quinolones
  • fluoroquinolones
  • metronidazole
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15
Q

over ___ million illnesses and ___ deaths are estimated to be as a result of antibiotic resistance

A
  • 2 million
  • 23,000
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16
Q

if the current trend continues, antibiotic resistant bacteria are expected to cause the premature death of ___ million people per year globally by 2050

A
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17
Q

___ is the rational, optimal use of antimicrobials

A

stewardship

all medical providers should behave as antimicrobial stewards

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18
Q

what are the 4 major antimicrobial resistance mechanisms?

A
  • restrict antibiotic access of drug to its target
  • modify antibiotic target
  • modify the antibiotic itself
  • modify expression of bacterial factors needed to activate the antibiotic (prodrugs)
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19
Q

describe restricting antibiotic access as an antimicrobial resistance mechanism

A
  • drug can’t get in or drug gets in but gets pumped back out before affecting target
  • ex. alter envelop to inhibit uptake or boost expression of efflux pumps
20
Q

describe antibiotic resistance by modification of the target

A
  • target is altered structurally or target is overexpressed, so you need much more of the drug
  • ex. mutation or gain of modifying enzyme (A2580G mutation in 23S rRNA protects against macrolides like erythromycin)
  • overexpression of target (change in promoter, regulator, or gene copy number)
21
Q

describe antibiotic resistance by inactivation of the antibiotic: beta-lactamase

A

beta lactamase breaks a bond in the beta lactam ring of penicillin to disable the molecule. bacteria with this enzyme can resist the effects of penicillin and other beta lactam antibiotics

22
Q

describe antibiotic resistance by modification of the antibiotic: aminoglycoside-inactivating enzymes

A
  • targets aminoglycosides
  • modifications disrupt hydrogen-boning network used to bind 16S rRNA
23
Q

what are two ways resistance is acquired?

A

mutation and horizontal gene transfer

24
Q

which 3 ways can resistance genes be transferred?

A

conjugation, transformation, and transduction

25
Q

in e. coli, resistance to streptomycin can arise due to spontaneous mutation at a rate of 1 in a billion. why is this important?

A

though rare, the fast growth rates and high numbers of bacteria mean that rare events like this become meaningful

26
Q

what are 4 important classes of multidrug resistant bacterial pathogens that are becoming increasingly common?

A
  • extended-spectrum beta lactamase producing enterobacteriaceae
  • carbapenem-resistant enterobacteriaceae
  • clostridium difficle
  • super neisseria gonorrhea
27
Q

describe extended-spectrum beta lactamase producing enterobacteriaceae

A

26,000 infections due to ESBL strains

1700 deaths per year

$40k excess costs per infection

28
Q

describe carbapenem-resistant enterobacteriaceae

A

>9000 healthcare associated infections are caused by CRE each year

about 600 deaths due to resistant klebsiella and e. coli strains per year

29
Q

describe clostridium difficile

A

250000 infections per year requiring hospitilization or affecting already hospitalized patients

14000 deaths per year

at least $1 billion in excess medical costs per year

30
Q

describe super neisseria gonorrhea

A

246000 drug-resistant infections per year (30% of total gonococcal infections)

31
Q

what 4 things contribute to the selection and spread of multi-drug resistant strains?

A

overuse of antibiotics, overpopulation, poor hygiene, and travel

32
Q

the number of new antibiotics developed and approved has steadily decreased in the past 3 decades, leaving fewer options to treat resistant bacteria. why?

A
  • development of new antibiotics is daunting: costs, pharmacokinetics, potential side effects
  • ideally target pathogens with minimal effects on beneficial microbiota
33
Q

describe antibiotic tolerance

A
  • bacteria that are normally susceptible to antibiotics may be able to tolerate the drugs under some conditions
  • antibiotic tolerance contributes to chronic and recurrent/relapsing infections (recrudescence)
  • antibiotic tolerance is important
    • within intracellular niches
    • spores
    • within biofilms
    • persister cell formation
34
Q

bacteria present within ___ are often protected from antibiotic treatments

A

biofilms

35
Q

>___% of human infections may involve biofilms

A

65

36
Q

biofilm formation enhances the ability of bacteria to tolerate antibiotics in what ways?

A
  • extracellular matrix
  • altered protein expression
  • decreased metabolism
  • persister cell formation
  • increased genetic exchange
  • increased stress resistance
37
Q

what are persister cells?

A

dormant bacteria that are insensitive to many stresses and antibiotic treatments

38
Q

antibiotics have a hard time killing ___, but may still reduce bacterial numbers enough so that the host can regain control.

A

persisters

39
Q

describe bacterial resistance to tetracycline as an antibiotic resistance mechanism. what is the mechanism of resistance?

A
  • tetracycline binds to the 16S rRNA in the 30S subunit
  • as a modifcation of the target, ribosomal mutation is achieved via mutation or horizontal gene transfer acquisition of a GTPase that perturbs the helix in the 16S rRNA
40
Q

a normal transpeptidase or penicillin-binding protein (PBP) is inactivated by penicillin, but penicillin no longer binds to the PBP with altered binding sites. This PBP is still able to carry out its cross-linking function so the beta lactam is no longer effective. what type of modification is this?

A

modification of the target

41
Q

a terminal amino acid substitution that no longer allows vacomycin to bind is an example of what type of modification?

A

modification of the target

42
Q

inactivation of an antibiotic by hydrolysis or by steric hinderance are examples of what type of modification?

A

antibiotic resistance by modification or inactivation of the antibiotic

43
Q

what are the 3 antibiotic modifications that disrupt hydrogen-bonding network used to bind the 16S rRNA? what type of enzymes are used?

A
  • N acetylation, O phosphorylation, and O adenylation
  • aminoglycoside-inactivating enzymes
44
Q

what are two prodrugs that bacterial resistance can be achieved against by modifying expression of bacterial factors needed to activate the antibiotic?

A

metronidazole and isoniazid

45
Q

describe how resistance to isoniazid can be achieved by modifying expression of the bacterial factor needed to activate it

A
  • isoniazid inhibits the synthesis of mycolic acids, required for the mycobacterial cell wall
  • isoniazid is activated by the bacteral catalase/peroxidase enzyme KatG in mycobacterium tuberculosis
  • modification of KatG will prevent activation of isoniazid, and mycolic acid synthesis will continue
46
Q

metronidazole requires activation by ___ in H. pylori and P. gingivalis

A

flavodoxin