Antimicrobial

resistance as an

emerging food-borne

infectious disease

How “superbugs” are grown in big farms and spread to

humans

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Pre-antibiotic era (1)

Traces of tetracycline in ancient Sudanese nubia

skeletons (350-550CE)

Use of artemisin in Traditional Chinese Medicine

But no or vey limited selection pressure: the genes are

present (genetic studies suggests that beta-lactamase

gene is evolving for 100 millions years in some bacteria

species (Fevre et al., 2005), but there is no differential

value in terms of selection and evolution.

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The rise of antibiotics (1) Antibiotic era:

1899: Emmerich and Löw, preparation of a substance

based on Pseudomonas aeruginosa extract, abandoned,

but found later to contain antibiotic substances

Precursors of modern antibiotics: Ehrlich and Hata, 1910.

Salvarsan and treatment of syphilis;

Fleming: discovery of Penicillin in 1929, but first medical

use in 1940, and mass production in 1945;

The end of infectious

diseases was announced

since the silver bullet was

supposed to be discovered …

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… and the fall of antibiotics:

antimicrobial resistance Definition (WHO): “resistance of a microorganism to an antimicrobial

medicine to which it was originally sensitive.”

Exponential acceleration of AMR acquired under an unprecedented

pressure selection due to a global misuse of antibiotics, including as growth

promoter for rising farm animals, but also shrimps, fish …

Nowadays, one of the major public health threat:

(1) In the EU antimicrobial multiresistance, it is:

25,000 deaths/year,

1.5 billions € for extra healthcare cost and loss of productivity

(1) in the USA, 63,000 patients die every year from hospital-acquired bacterial infections

Limits treatment options, raises healthcare costs, and increases the

number, severity, and duration of infections (2)

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Antimicrobial resistance in Asia Hospitals= « multiresistant bacteria factory »: (3) in HCMC tertiary hospital, 190

patients: 34.0% methicillin-resistant Staphylococcus aureus (MRSA), 61.3% extended

spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (excluding Klebsiella

pneumoniae), 53.4% Pseudomonas aeruginosa, 65.7% gentamicin-resistant K.

pneumoniae, and 57.1 % amikacin-resistant Acinetobacter.

Food chain= very common mode of transmission of resistant bacteria (≠

transmission of resistance from bacteria to bacteria) from animals to humans. Ex. of

Salmonella (typhoid fever pathogen):

(4), in Vietnam, 48.7% chicken carcass Salmonella-positive; 73.3% resistant to a least 1

antibiotic, and 17.7% multiresistant strains

(5) Multidrug resistant salmonella among humans in Vietnam: 50%, stable between 1993 and

2005; resistance to nalidixic acid increased from 4% to 97%;

(5): 381 Typhi strains from 8 Asian countries - Bangladesh, China, India, Indonesia, Laos,

Nepal, Pakistan, and central Vietnam - collected in 2002 to 2004: multidrug resistance: from

16 to 37%; nalidixic acid resistance: 5 to 51%.

The eight Asian countries involved in this study are home to 80% of the world's typhoid fever

cases.

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The study of Stuart B. Levy: ubiquitous,

traveling antimicrobial resistance – findings

(6)

1975-76: prospective study, introduction of antibiotic-laced food

in chicken free of other any antibiotic use.

Chicken that didn’t eat this food and separated from the

batch that received it were excreting tetracyclin-resistant

E.coli after 48h, and multiresistant E. coli after 3 months

Farm families were also excreting E. coli resistant to ATB

People in the neighborhood excreted other bacteria – not

E.coli – that were have acquired resistance to many other

antibiotics

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The study of Dr. Stuart B. Levy: ubiquitous,

traveling antimicrobial resistance -

conclusions Lessons learnt from Dr. Levy’s studies:

a non therapeutic dose of antibiotics used as growth promoter can

induce antimicrobial resistance among other animals not directly

exposed to this ATB

A non therapeutic dose of antibiotics used as growth promoter can

induce antimicrobial resistance to other antibiotics among non

exposed farm animals

A non therapeutic dose of antibiotics in raising farm animals can

induce antimicrobial resistance to non directly exposed human

population around.

Further studies: antimicrobial resistance can be transmitted from

animals to animals and to humans without the use of any

antibiotics, in a farm setting (multi)resistant bacteria can be

found in almost all kind of environment, not only hospital settings.

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The big picture of antimicrobial

resistance

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How come? …Transmission of

resistance genes Resistance is transmitted by another genetic material than

chromosomal DNA: the plasmids:

Observation of 4-drugs resistant E. coli: 1 mutation in 10 millions doublings 1/(10*10^6)^4 =1/10^28 doublings

Another DNA support: plasmids

Plasmids carry the resistance genes, and other functionalities (antibacterial protein synthesis, virulence, …)

Horizontal transmission to any other kind of bacteria

Provide a selective advantage when under the pressure of antibiotics

Also used to clone genes in cells (genetically engineered human insulin) …

Other means of transfer of a gene resistance from bacteria to bacteria: transfer of free DNA, and viral transmission.

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Mechanisms of transmission

of resistance genes

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Food safety …

goes far beyond the classic conception of « food-borne

disease »;

is a necessary even though not sufficient mean of

control of antimicrobial resistance from environmental

origin;

is not only about tackling bacteria from food, but also

looking upstream to sustainable and eco-responsible

animal farming.

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Solution#1: Be a smart

consumer

Be curious and aware of the origin of your food:

Ask questions to the vendors, pay a visit to the producers;

Be an open-minded activist, push towards Eco-

responsibility and promote sustainable farming and

agriculture in all the circles you belong to;

Buy local food: the closer to the producer, the more

likely you are able to get a reliable information of the

origin of the food and the method of production.

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Solution#2: Be a smart

producer or farmer

Promote an appropriate use of antibiotic use in food

animals:

« To slow the pace of antibiotic resistance, emergence, and

spread, the use of antimicrobials for animal growth

promotion should be terminated. » (7)

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Solution #3: be a smart patient

Antibiotics are double-edged weapons:

Question your doctor for every antibiotics prescription;

Do not think that a common cold is treated with antibiotics;

An individual antibiotic treatment has an impact on all the

communities you belong to (family, workplace,

neighborhood, city, province, country, … Earth).

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"Antibiotics are uniquely societal drugs because

individual use affects others in the community and

environment. Better stewardship, incentives, and

establishment of a special regulatory category will

improve how they are used, marketed, and developed

through incentives to industry. »

Stuart B. Levy, M.D. President of APUA, professor at Tufts University School of Medicine From the IOM 25th Anniversary Symposium (1996) and The Antibiotic Paradox (2002)

Accessed on 24 February 2014 at http://www.tufts.edu/med/apua/index.shtml

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References

1. A Brief History of the Antibiotic Era: Lessons Learned and Challenges for the Future. Aminov Rustam I. Front. Microbiol., 08 December 2010 | doi: 10.3389/fmicb.2010.00134

2. B. Marshall and S. Levy. “Food Animals and Antimicrobials: Impacts on Human Health”(2011) Clinical Microbiology Review 24,4:718-733

3. Effects of infection control measures on acquisition of five antimicrobial drug-resistant microorganisms in a tetanus intensive care unit in Vietnam. Constance Schultsz, Martinus C. J. Bootsma, Huynh T. Loan, et al. Intensive Care Med (2013) 39:661–671. DOI 10.1007/s00134-012-2771-1

4. Quantification, serovars, and antibiotic resistance of salmonella isolated from retail raw chicken meat in Vietnam. Ta YT, Nguyen TT, To PB, Pham da X, Le HT, Thi GN, Alali WQ, Walls I, Doyle MP. J Food Prot. 2014 Jan;77(1):57-66. doi: 10.4315/0362-028X.JFP-13-221.

5. Antimicrobial drug resistance of Salmonella enterica serovar typhi in asia and molecular mechanism of reduced susceptibility to the fluoroquinolones. Chau TT et al., Antimicrob Agents Chemother. 2007 Dec;51(12):4315-23. Epub 2007 Oct 1.

6. The Antibiotic Paradox: How the Misuse of Antibiotics Destroys Their Curative Powers. Second edition. By Stuart B. Levy. 353 pp., illustrated. Cambridge, Mass., Perseus Publishing, 2002. $17.50. ISBN: 0-7382-0440-4

7. APUA: Alliance for the Prudent Use of Antibiotics. http://www.tufts.edu/med/apua/ @APUANews

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