Antibiotics and Antibiotic Resistance Flashcards

1
Q

What are the 3 antimicrobial agents

A
  • Disinfectants
  • Antiseptics
  • Antibiotics
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2
Q

What are disinfectants?

A

Antimicrobial agents that are applied to inanimate objects (e.g. floors, tables, walls etc.)

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3
Q

What are antiseptics?

A

Antimicrobial agents that are sufficiently non-toxic to be applied to living tissues (e.g. hand sanitizers)

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4
Q

What are antibiotics?

A

antimicrobial agents produced by bacteria and fungi that are exploited by humans (delivered topically and internally)

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5
Q

Describe what antibiotics are useful for

A
  • very effective therapeutic against bacterial infections
  • availability of antibiotics enable cancer chemotherapy, organ transplantation, all invasive surgeries, and the treatment of premature infants
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6
Q

What are the 2 major problems when dealing with antibiotics?

A
  • Bacterial resistance to antibiotics always happens

- Diminished interest fro pharmaceutical companies to develop new antibiotics

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7
Q

Describe the types of misuse of antibiotics

A
  • Empiric use (blinded use)
  • Increased use of broad-spectrum agents
  • Pediatric use for viral infections
  • Patients who do not complete course
  • Antibiotics in animal feed
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8
Q

What are the different ways we can measure antibiotic activity?

A
  • minimum inhibitory concentration (MIC)
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9
Q

What is minimum inhibitory concentration?

A
  • series of culture tubes with varying concentration of agent
  • check for visible growth
  • the lowest concentration of agent that inhibits the growth
  • antibiotic strips
  • faster, multiple antibiotics
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10
Q

How do antibiotics works?

A
  • target essential bacterial components
  • cell wall synthesis
  • protein synthesis
  • DNA/RNA synthesis
  • foliate synthesis
  • cell membrane alteration
  • targets are not present (or different) in eukaryotic cells
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11
Q

What is a penicillin-like “beta” lactam antibiotic?

A
  • contains a “B lactam ring”
  • function to inhibit cell wall synthesis in bacteria
  • bind the bacterial “penicillin-binding proteins (PBPs)
  • some bacteria can produce a B lactamase
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12
Q

What are penicillin-binding proteins

A
  • are transpeptidases
  • no peptide cross-links
  • weak cell wall
  • cell death
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13
Q

What is B lactamase?

A
  • an enzyme that destroys the ring and thus the antibiotic
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14
Q

What is a methicillin-like “beta” lactam antibiotic?

A
  • contains a “B lactam ring”
  • chemically modified penicillin
  • can’t be cleaved by B lactamases
  • some bacteria can produce a different “penicillin-binding protein” (e.g. PBP2a)
  • encoded by ‘mec’
  • PBP2a doesn’t bind methicillin (or other B lactams)
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15
Q

What is Vancomycin?

A
  • a glycopeptide antibiotic
  • inhibits cell wall synthesis in gram positives
  • often a drug of “last resort”
  • binds the peptide linkage at terminal D-ala-D-ala residues and inhibits transpeptidation
  • resistance genes change theses to D-ala-D-Lac and vancomycin can no longer bind
  • resistance is encoded by the van genes
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16
Q

What are the bacterial strategies for antibiotic resistance

A

Prevention of antibiotic entry
- gram-negative outer membrane and mycobacteria cell wall

Antibiotic modification
- B lactamase

Efflux of antibiotic
- actively pump out the antibiotic

Alteration of antibiotic target
- PBPs, ribosome modifications

Bypassing the antibiotic action
- use environmental folic acid

17
Q

Antibiotic resistance genes

A
  • many mechanisms of antibiotic resistance are genetically encoded
  • can produce very high levels of antibiotic resistance
  • often encoded on mobile genetic elements (plasmids) allowing for horizontal gene transfer -> “superbugs”
18
Q

What is horizontal gene transfer?

A
  • rather than alter gene function through mutations, new genes are acquired from another source
  • transformation
  • transduction
  • conjugation
19
Q

What is klebsialla pneuomoniae

A
  • gram-negative
  • an important cause of nosocomial pneumonia
  • produces a capsule and is commonly resistant to multiple antibiotics
  • first documented source of “NDM-1”
20
Q

What is NDM-1

A
  • New Delhi Metallo-beta-lactamase-1
  • also known as a carbapenemase
  • carbapenem antibiotics are B-lactamase resistance B-lactams with broad-spectrum activity
  • is now widespread in other gram-negatives
  • CRE (carbapenem-resistant Enterobacteriaceae)
21
Q

What are clostridia?

A
  • gram-positive
  • rod-shaped
  • endospore-formers
  • strict anaerobes, vegetative cells killed by O2
  • generally found in soil and intestinal tracts of animals
  • can cause life-threatening disease mediated by exotoxins
22
Q

What are some important clostridia human pathogens?

A

C. difficile
- pseudomembranous colitis

C. tetani
- tetanus

C. botulinum
- botulism

C. perfringens
- food-borne illness and gas gangrene

23
Q

What can C. difficile exist as

A
  • asymptomatic carrier state in the large intestine
  • cause of mild to moderate diarrhea
  • cause of life-threatening pseudomembranous colitis
24
Q

Where can C. difficile be found in?

A
  • nursing home and hospital environments

- nosocomial pathogen

25
Q

C. difficile endospores

A
  • can be very difficult to eradication from the environment

- culture from the floor, bedpans, toilets, hands and clothing of medical personnel

26
Q

What is the mode of transmission of C. difficile

A
  • through the spore: fecal-oral route
27
Q

What is pseudomembranous colitis?

A
  • most symptomatic patients have recently revived an antimicrobial agent
  • an inflammatory condition of the large intestine
  • offensive smelling diarrhea, abdominal pain, fever, nausea dehydration
  • symptoms may occur 1-2 days after antibiotics or several weeks after the antibiotic is discontinued
28
Q

Pseudomembranous colitis lesions

A
  • show characteristic yellow lesions
  • ## can enlarge to cover substantial portion s of inflamed mucosa and can be stripped off from the pseudomembrane
29
Q

Pseudomembranous colitis treatment

A
  • antibiotics are used to cure infections, but they also kill the normal microbiota
  • suppression of normal microbiota and persistence of C. difficile endospores
  • after the antibiotic is stopped, spores germinate, overgrowth of C. difficile occurs with the production of toxins
  • does not itself invade, but the toxins damage the intestinal lining of the large intestine
30
Q

What are the toxins produced by C. diff

A
  • A-B toxins called the large clostridial cytotoxins

- serves to designate two domains

31
Q

What does the A domain do?

A

Denotes the active portion of the toxin that carries the enzymatic activity

  • function to inactivate key regulatory protein of host cells
  • causes dysregulation of multiple cellular processes including cytoskeletal rearrangements, cell death and inflammation
32
Q

What does the B domain do?

A

Denotes the portion of the toxin molecule responsible for binding and uptake by the host cell

33
Q

Diagnosis and treatment

A
  • history (antibiotic use), symptoms and laboratory test to confirm C. difficile
  • endoscopy and toxin detection assay
  • discontinue inciting antibiotic if still being used
  • fluids for treatment
  • antibiotics more specific for “C. diff” - oral vancomycin or I.V. metronidazole
  • avoid antidiarrheal agents - would cause decreased toxin clearance