Antibiotics in the food supply

Question 1

What was the first antibiotic and when it was discovered?

Answer 1

Discovered in 1928, penicillin

Question 2

Why antiobiotics is not a simple question/answer?

Answer 2

Question 3

What three sites antibiotics can attack

Answer 3

Cell wall, DNA or ribosomes

Question 4

Bactericidal antibiotics target what site?

Answer 4

Cell wall

Question 5

Name drugs for cell wall antibiotics

Answer 5

Question 6

Name drugs targeting DNA of bacteria

Answer 6

Question 7

Name drugs that target ribosomes

Answer 7

Question 8

How much of all antibiotics used are in agriculture in Canada

Answer 8

80%

Question 9

How beta-lactams resistance work

Answer 9

• 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

Question 10

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

Answer 10

Beta-lactam ring

Question 11

How synthetic alternatives to penicillins are made?

Answer 11

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

Question 12

How general resistance to beta-lactams can develop?

Answer 12

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

Question 13

what are two specific resistance to beta-lactams?

Answer 13

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

Question 14

Two types of resistance to antibiotics:

Answer 14

General and specific

Question 15

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

Answer 15

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

Question 16

The timeline of antibiotics invention and use

Answer 16

• 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

Question 17

In what countries Antibiotic growth promoters (AGPs) are banned

Answer 17

Sweden and other nordic countries

Question 18

What antibiotics are banned in US; China and India?

Answer 18

• 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

Question 19

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

Answer 19

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

Question 20

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

Answer 20

• 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

Question 21

What antibiotics are eliminated in chicken farms in Canada

Answer 21

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

Question 22

Countries that use the most antibiotics

Answer 22

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

Question 23

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?

Answer 23

I- 3rd Cephalosporins

II-Streptogramins

III- Bacitracins

IV-Ionophores

Question 24

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

Answer 24

•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

Question 25

Does Banning Antibiotics work?

Answer 25

* 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.

Question 26

Is elimination of antibiotics effective? give example based on ceftiofur

Answer 26

Question 27

Virginiamycin and cross resistance

Answer 27

* **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**

Question 28

Bacitracin and cross resistance

Answer 28

* 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

Question 29

Is use of antibiotics justified?

Answer 29

* 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

Question 30

How ARGs are moving from farms?

Answer 30

• **Water, Soil, Farmers, and Food** ## Footnote * 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

Question 31

Does ARGs stay on one continent?

Answer 31

Question 32

How vegetables can be contaminated with ARGs and ARBs

Answer 32

* 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

Question 33

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

Answer 33

Question 34

what implications of no antimicrobials there is for organic farming?

Answer 34

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

Question 35

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

Answer 35

Question 36

Are antibiotics used in plant production?

Answer 36

* 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

Question 37

What is the situation with antibiotics in aquaculture?

Answer 37

* 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.

Question 38

What are the two schoold of though in AMR Food chain

Answer 38

Question 39

What is colistin?

Answer 39

* **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

Question 40

What is the situation with colsitin AMR

Answer 40

* 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.

Question 41

How disk diffusion method works for confirming antibiotic resistance?

Answer 41

Question 42

MIC test strips for antibiotic resistance: principle

Answer 42

Question 43

What is Sensititre MIC plate?

Answer 43

Question 44

How AMR can be else detected except disk plates and MIC

Answer 44

•AMR can be detected from the whole genome sequences of bacteria The Comprehensive Antibiotic Resistance Database is a tool to help with this

Question 45

What methods can help with antibiotic resistance

Answer 45

Finish antibiotics Do not eat antibiotics without prescription

Question 46

How AMR is transferred betwen animals and humans: summary

Answer 46