Antibiotics in the food supply Flashcards
What was the first antibiotic and when it was discovered?
Discovered in 1928, penicillin
Why antiobiotics is not a simple question/answer?
What three sites antibiotics can attack
Cell wall, DNA or ribosomes
Bactericidal antibiotics target what site?
Cell wall
Name drugs for cell wall antibiotics
Name drugs targeting DNA of bacteria
Name drugs that target ribosomes
How much of all antibiotics used are in agriculture in Canada
80%
How beta-lactams resistance work
- 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
What structure is very important in penicillin and synthetic beta-lactams for binding?
Beta-lactam ring
How synthetic alternatives to penicillins are made?
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
How general resistance to beta-lactams can develop?
- Penetration – Intracellular bacteria are resistant to beta-lactams if they are in a mammalian cell
- 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)
- Pumps – Gram-negative bacteria can express ABC transporters to pump antibiotics out of the cell
- Peptidoglycan is absent – Some bacteria like mycobacteria lack a cell wall, and are thus not affected by beta-lactam antibiotics
what are two specific resistance to beta-lactams?
- Penicillinases – Some bacteria can make beta-lactamases that degrade beta-lactam antibiotics before they reach the cell
- 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
Two types of resistance to antibiotics:
General and specific
Type of mechanisms for AMR, Action (specific or non specific) and what antibiotics are prone to it?
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
The timeline of antibiotics invention and use
- 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
In what countries Antibiotic growth promoters (AGPs) are banned
Sweden and other nordic countries
What antibiotics are banned in US; China and India?
- 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
what non-medical AGPs are still commonly used and the exception
•Non-medical AGPs including bacitracin, and bambermycin are still commonly included in animal rations (except in the EU)
What is done in dairy farms in Canada and US after each lactation? On what farms it is not done
- 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
What antibiotics are eliminated in chicken farms in Canada
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
Countries that use the most antibiotics
Spins, Germany, Italy, Portugal (EU a lot)
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?
I- 3rd Cephalosporins
II-Streptogramins
III- Bacitracins
IV-Ionophores
How much antimicrobial resistance death are costing every year and what is the projections of death by 2050?
•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
Does Banning Antibiotics work?
- 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.
Is elimination of antibiotics effective? give example based on ceftiofur
Virginiamycin and cross resistance
- 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
Bacitracin and cross resistance
- 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
Is use of antibiotics justified?
- 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
How ARGs are moving from farms?
• 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
Does ARGs stay on one continent?
How vegetables can be contaminated with ARGs and ARBs
- 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
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
what implications of no antimicrobials there is for organic farming?
•In organic farming (no antimicrobials) the prevalence of Salmonella, Toxoplasma, and Campylobacter all tend to be much higher
How EU and Denmark is doing with antibiotics ban and progress?
Are antibiotics used in plant production?
- 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
What is the situation with antibiotics in aquaculture?
- 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.
What are the two schoold of though in AMR Food chain
What is colistin?
- 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
What is the situation with colsitin AMR
- 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.
How disk diffusion method works for confirming antibiotic resistance?
MIC test strips for antibiotic resistance: principle
What is Sensititre MIC plate?
How AMR can be else detected except disk plates and MIC
•AMR can be detected from the whole genome sequences of bacteria
The Comprehensive Antibiotic Resistance Database is a tool to help with this
What methods can help with antibiotic resistance
Finish antibiotics
Do not eat antibiotics without prescription
How AMR is transferred betwen animals and humans: summary
