This document summarizes the rise of antimicrobial resistance as a growing public health issue linked to overuse of antibiotics in agriculture. It discusses how non-therapeutic use of antibiotics as growth promoters in farm animals has led to widespread resistance in bacteria. Studies show resistant bacteria can spread between animals on a farm and from animals to nearby humans and environment even without antibiotic use. The overuse of antibiotics in medicine and agriculture has accelerated resistance by placing intense selective pressure on bacteria. Widespread antibiotic resistance now compromises treatment of bacterial infections in humans. Solutions proposed include restricting non-therapeutic antibiotic use in animals and more prudent antibiotic prescribing and use by medical professionals and consumers.

1. Antimicrobial
resistance as an
emerging food-borne
infectious disease
How “superbugs” are grown in big farms and spread to
humans
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2. 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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3. 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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4. … 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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5. 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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6. 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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7. 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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8. The big picture of antimicrobial
resistance
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9. 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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10. Mechanisms of transmission
of resistance genes
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11. 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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12. 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 Ecoresponsibility 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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13. 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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14. 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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15. "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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16. 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/s00134012-2771-1
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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