Antibiotics in the food supply Flashcards

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1
Q

What was the first antibiotic and when it was discovered?

A

Discovered in 1928, penicillin

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2
Q

Why antiobiotics is not a simple question/answer?

A
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3
Q

What three sites antibiotics can attack

A

Cell wall, DNA or ribosomes

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4
Q

Bactericidal antibiotics target what site?

A

Cell wall

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5
Q

Name drugs for cell wall antibiotics

A
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6
Q

Name drugs targeting DNA of bacteria

A
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7
Q

Name drugs that target ribosomes

A
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8
Q

How much of all antibiotics used are in agriculture in Canada

A

80%

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9
Q

How beta-lactams resistance work

A
  • In the absence of a beta-lactam antibiotic, transpeptidases, also known as penicillin binding proteins catalyze the cross links between glycan changes in the peptidoglycan
  • The result is covalent bonds between the peptide and sugar chains that create a rigid cell wall that protects the bacterial cell from osmotic forces that can result in cell rupture
  • Beta-lactam antibiotics, are similar to the natural peptidoglycan subunits (D-Ala-D-ala) that are the substrate for the transpeptidases.
  • These antibiotics bind strongly to the active site in the transpeptidase and stop cell wall synthesis
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10
Q

What structure is very important in penicillin and synthetic beta-lactams for binding?

A

Beta-lactam ring

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11
Q

How synthetic alternatives to penicillins are made?

A

Chemical modification of the structure of penicillins led to the development of synthetic beta-lactams – which have greater spectrums of activity, and greater resistance to beta-lactamases, as well as different pharmacokenetic properties

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12
Q

How general resistance to beta-lactams can develop?

A
  1. Penetration – Intracellular bacteria are resistant to beta-lactams if they are in a mammalian cell
  2. Porins – Gram-negative bacteria are resistant to beta-lactams since the outer cell membrane protects the peptidoglycan, but porins can allow beta-lactams inside. However, some Gram-negatives have smaller porins that excludes beta-lactams (general)
  3. Pumps – Gram-negative bacteria can express ABC transporters to pump antibiotics out of the cell
  4. Peptidoglycan is absent – Some bacteria like mycobacteria lack a cell wall, and are thus not affected by beta-lactam antibiotics
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13
Q

what are two specific resistance to beta-lactams?

A
  1. Penicillinases – Some bacteria can make beta-lactamases that degrade beta-lactam antibiotics before they reach the cell
  2. PBPs – Some bacteria can express mutated transpeptidases that still has the enzymatic activity for cell wall synthesis, but does not bind to beta-lactam antibiotics
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14
Q

Two types of resistance to antibiotics:

A

General and specific

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15
Q

Type of mechanisms for AMR, Action (specific or non specific) and what antibiotics are prone to it?

A

DNA gyrase is an essential bacterial enzyme that catalyzes the ATP-dependent negative super-coiling of double-stranded closed-circular DNA.

RNA polymerase is an enzyme that is responsible for copying a DNA sequence into an RNA sequence

Beta lactamase and cephalasporinases act on the antibiotic

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16
Q

The timeline of antibiotics invention and use

A
  • Sulfonamides were first marketed as Antibiotic Growth Promoters (AGPs) in 1938
  • Gramicidin was successfully used to treat a mass outbreak of mastitis in dairy cows in 1940
  • In 1948, sulfaquinoxaline was the first antibiotic licensed for inclusion in poultry feed to prevent coccidiosis
  • A few years later, it was shown that subtherapeutic doses had growth promoting effects in poultry
  • In the 1950s the beef industry switched from low-density grazing to high-intensity feed-lot systems
  • Chlortetracycline, oxytetracycline, and bacitracin all used at some point
  • Bacitracin and ionophores still commonly used
  • Between 1951 and 1970 agricultural use of antibiotics increased >30-fold
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17
Q

In what countries Antibiotic growth promoters (AGPs) are banned

A

Sweden and other nordic countries

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18
Q

What antibiotics are banned in US; China and India?

A
  • USA has banned the use of cephalosporins and fluoroquinolone in agriculture and has also released guidelines to phase out antibiotic use
  • India and China have banned colistin use in agriculture, and are attempting to phase out AGPs
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19
Q

what non-medical AGPs are still commonly used and the exception

A

•Non-medical AGPs including bacitracin, and bambermycin are still commonly included in animal rations (except in the EU)

20
Q

What is done in dairy farms in Canada and US after each lactation? On what farms it is not done

A
  • Most dairy cattle in Canada and US are treated with intramammary ceftiofur hydrochloride and penicillin combinations after each lactation to prevent mastitis (Blanket Dry Cow Therapy)
  • Organic dairy farms do not do this
  • Some dairy farms (~20%) are practicing selective dry cow therapy
21
Q

What antibiotics are eliminated in chicken farms in Canada

A

Chicken Farmers of Canada eliminated the use of Category I antibiotics in 2014, Category II antibiotics by 2018 and are attempting to eliminate the preventive use of Category III antibiotics

22
Q

Countries that use the most antibiotics

A

Spins, Germany, Italy, Portugal (EU a lot)

23
Q

Table categories of antibiotics, their “name”, a representative from each class, and yes/no for preferred option for treatment of serious human infections and if alternatives available?

A

I- 3rd Cephalosporins

II-Streptogramins

III- Bacitracins

IV-Ionophores

24
Q

How much antimicrobial resistance death are costing every year and what is the projections of death by 2050?

A

•This cost our health care system $2billion dollars

•Current projections indicate that 10 million people will die each year due to AMR infections by 2050

25
Q

Does Banning Antibiotics work?

A
  • Yes. After bans you see a leveling off, and even a decrease of the AMR in the community.
  • However, banning based on Category may be problematic•The use of Category IV antibiotics can also contribute to medically important antibiotics in both human and veterinary use.
26
Q

Is elimination of antibiotics effective? give example based on ceftiofur

A
27
Q

Virginiamycin and cross resistance

A
  • Virginiamycin is commonly used in the poultry and swine industries
  • Virginiamycin acetyltransferases confer resistance to virginiamycin
  • Synercid is a semisynthetic antibiotic that combines dalfopristin and quinupristin
  • Synercid is used to treat MRSA infections in humans
  • Virginiamycin acetyltransferases also confer resistance to synercid
28
Q

Bacitracin and cross resistance

A
  • Bacitracin is commonly used in the poultry and swine industries
  • MCR-1 confers resistance to colistin
  • MCR-1 also confers resistance to bacitracin
  • The use of bacitracin may select for the MCR-1 gene
29
Q

Is use of antibiotics justified?

A
  • Antibiotics in agriculture make food cheaper, decrease land use required for animal products (grazing space and feed production space), and improve animal welfare (in high-density environments)
  • AGPs improve the growth rate in pigs by about 4.2%
  • Before blanket dry cow therapy there were 95% more cases of bovine mastitis than there are today
  • The mortality rate of poultry in organic farms is 4.2% compared with 2.9% in conventionally raised broilers (the USA produces 10 billion broilers annually)
  • Organic birds have a higher rate of eye burns, footpad lesions, and airsacculitis each of which are indicators of poor welfare
  • It is likely possible to achieve all of the same outcomes via better biosecurity – antibiotics are often used to compensate for poor hygiene by agricultural producers
30
Q

How ARGs are moving from farms?

A

Water, Soil, Farmers, and Food

  • 100% of meat products tested by my undergraduate class yield at least 1 MDR isolate every year
  • Very little systematic work done on non-pathogens in this area
  • Manure is usually spread on fields
  • Fields produce vegetables that are eaten raw
  • Animal farms are often located close to fruit and vegetable farms (think Salinas valley)
  • Soils are contaminated and ARGs can wash into rivers
  • Farmers are colonized with MRSA at a rate >760-fold higher than the general population•Veterinarians are colonized at >2-fold higher than the general population
31
Q

Does ARGs stay on one continent?

A
32
Q

How vegetables can be contaminated with ARGs and ARBs

A
  • Antibiotics used in food-producing animals help select for the presence of antibiotic resistance genes (ARGs) and antibiotic resistant bacteria (ARBs)
  • When manure is spread in soil and onto crops these ARGs and ARBs mix with environmental ARGs and ARBs, and if they are selected for can become more antimicrobial resistant
  • Current manure processing techniques are ineffective at removing ARGs from the manure
  • If vegetables are eaten raw, you may be consuming several ARBs and ARGs
33
Q

Aminoglycosides, beta-lactams, chlrooamphenicol, macrolids, polypeptides, fluoroquinolones, streptogramins, sulfonamides, tetracyclins: examples of each class’ mode of action/spectrum, species used on; put a cross if: used for disease prevention, disease treatment, growth promotion human use

A
34
Q

what implications of no antimicrobials there is for organic farming?

A

•In organic farming (no antimicrobials) the prevalence of Salmonella, Toxoplasma, and Campylobacter all tend to be much higher

35
Q

How EU and Denmark is doing with antibiotics ban and progress?

A
36
Q

Are antibiotics used in plant production?

A
  • To a much lesser extent antimicrobials are also used in plant production
  • Fruit plants may be sprayed with oxytetracycline and streptomycin, but we don’t conduct surveillance in this area so its hard to know the prevalence
37
Q

What is the situation with antibiotics in aquaculture?

A
  • Few antibiotics are available for aquaculture in the US (sulfadimethoxine, ormetoprim, sulfamerizine, and oxytetracycline)
  • However, the use in other countries is unknown and presumed to be higher
  • The presence of antibiotic residues in imported seafood is a common reason for seizure.
38
Q

What are the two schoold of though in AMR Food chain

A
39
Q

What is colistin?

A
  • Colistin, also known as polymyxin E, is a very old antibiotic that was not used in humans due to kidney toxicity. However, due to the spread of AMR use became more prevalent in the 1990’s
  • However, it remains a last-resort antibiotic for multidrug-resistant (MDR) Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter in emergency situations, despite its toxicity
40
Q

What is the situation with colsitin AMR

A
  • The mobilized colistin resistance (mcr-1) gene was discovered in 2011, but it existence was published in the scientific literature in 2015
  • It was isolated from E. coli from a pig in China
  • This gene confers plasmid-mediated resistance to colistin (is this bad?)•MCR is capable of horizontal gene transfer between different species
  • It has now been found in E. coli, Salmonella enterica, Klesiella pneumonia, Enterobacter aerogenes, and Enterobacter cloacae
  • It had been detected in 30 countries (including Canada) in less than a year. In Canada mcr-1 was found in E.coli extracted from ground beef.
41
Q

How disk diffusion method works for confirming antibiotic resistance?

A
42
Q

MIC test strips for antibiotic resistance: principle

A
43
Q

What is Sensititre MIC plate?

A
44
Q

How AMR can be else detected except disk plates and MIC

A

•AMR can be detected from the whole genome sequences of bacteria

The Comprehensive Antibiotic Resistance Database is a tool to help with this

45
Q

What methods can help with antibiotic resistance

A

Finish antibiotics

Do not eat antibiotics without prescription

46
Q

How AMR is transferred betwen animals and humans: summary

A