The Other Side of Antimicrobial Resistance

An editorial was recently published by Bill Marler’s group entitled “Letter from the Editor: Antibiotic Resistance.”(1) For the most part, I agree with this article. However, there are a few points that I think need clarification. I will use a “point-counter point” approach, although not all of these counterpoints are arguments.

Point: “Antibiotics are integral in the treatment of many food-borne diseases, making this an important issue for the food safety community.”

Counter point: Yes, antimicrobial resistance (AMR) is a big deal. Antimicrobials are used in treating infections. However, they are not the first line of defense for treating food-borne illness, even in cases requiring hospitalization. Instead, the primary course of treatment is fluid therapy.(2) Therefore, even if we could erase AMR in food-borne pathogens, it is unlikely that there will be a significant improvement in the outcome of food-borne illness cases.

Point:

Drug-resistant infections take a staggering toll in the United States and across the globe. Just one organism, methicillin-resistant Staphylococcus aureus (MRSA), kills more Americans every year than emphysema, HIV/AIDS, Parkinson's disease, and homicide combined. Nearly 2 million Americans per year develop hospital-acquired infections (HAIs), resulting in 99,000 deaths - the vast majority of which are due to antibacterial-resistant pathogens. Two common HAIs alone (sepsis and pneumonia) killed nearly 50,000 Americans and cost the U.S. health care system more than $8 billion in 2006.

Counterpoint: The impact of AMR is staggering. Resistant infections have been a problem since the discovery of penicillin, which is the reason for the invention of multiple types of antibiotics.(3) It is also important to realize that very few of the bacteria listed in the above paragraph are related to livestock and food. In addition, several other medically important bacteria, such as Pseudomonas aeruginosa, Streptococcus pneumoniae, and Mycobacterium tuberculosis, have resistance patterns that cannot be explained from livestock antimicrobial usage.(4)

Point: “Antibiotics are becoming less and less effective, in part due to over-prescription and inappropriate use.”

Counter point: I don’t really disagree with this point but I would like to “fine tune” it a bit. As soon as an antibiotic is first used, resistance begins to develop. Bacteria evolve under the selection pressure of antibiotic exposure. It is how they survive. Inappropriate or unnecessary use means extra pressure on the bacterial population, thus increasing the speed of evolution.

To the extent that agriculture is guilty for antimicrobial resistance, we repent. It is important to note that many producer groups are making major efforts to become more prudent in antimicrobial use, just like what is being done in human medicine.

Point: “If I am reading scientists correctly, there are multiple theories for antibiotic resistance and agreement that some occurs naturally in the environment. Some of these theories involve antibiotic uses by both humans and animals.”

Counter point: Both points are correct. The ability to resist antibiotics has been around since the first microbe. Many types of antimicrobial resistance were recently discovered in four million year old dirt that had never been touched by man or beast.(5) Subsequently, any antimicrobial usage, even if appropriate, allows the resistant strains to become more prominent.

Point: “Yet, is it just me, or is antibiotics used in animal agriculture the only thing we hear about when antibiotic resistance comes up? Am I wrong to look at antibiotic resistance as a big circle with animal issues maybe involving a 25 percent slice with lots of other unknowns out there?”

Counter point: No counter argument here. You are correct! Agriculture is taking way too much of the heat for its contribution to antibiotic resistance, and all published risk assessments show this contribution to be negligible. I would venture to say the percentage is much less that 25%. One paper I published shows the average American is more likely to die from a bee sting (1 in 6 million) than to get a few extra days of diarrhea due to macrolide (a common animal antibiotic) use in livestock.(6,7)

Point: “I just have this feeling that allowing animal diseases to go untreated would not contribute to food safety.”

Counter point: Again, I agree. Failure to treat or prevent illness leads to needless animal suffering. Additionally, some new research is showing that healthy animals that have recovered from a respiratory or infectious illness are more likely to be contaminated with foodborne pathogens such a Salmonella or Campylobacter.(8,9)

Point: “Antibiotic resistance is complex issue. Help direct our coverage by suggesting people we should talk to and places we should go. Where's the cutting edge research being done? This is not just some problem on the farm we haven't solved. It's bigger, broader, and more complex. Now, please submit your answers.”

Counter point: Amen brother. There many questions that have not been addressed. If society was not so busy pushing draconian and meaningless solutions such as the PAMTA (Preservation of Antibiotics for Medical Treatment Act) or collecting usage data without good data on resistance, then resources would be available to answer many of your thoughtful questions.

References:
1Flynn, D. 2012. Letter from the Editor: Antibiotic Resistance.
http://www.foodsafetynews.com/2012/08/letter-from-the-editor-antibiotic-resistance/#.UFeIPbKPU-I

2Food Poisoning Center, Sanford, FL. 2011. What is the treatment for food poisoning?
http://www.medicinenet.com/food_poisoning/page6.htm#what_is_the_treatment_for_food_poisoning

3D’Costa, V. et al. 2011. Antibiotic Resistance is ancient. Nature 477:457-461
http://www.nature.com/nature/journal/v477/n7365/full/nature10388.html

4Bywater, R.J., Casewell, M.W. 2000. An Assessment of the impact of antibiotic resistance in different bacterial species and of the contribution of animal sources to resistance in human infections. Journal of Antimicrobial Chemotherapy 46(4):643-645. http://jac.oxfordjournals.org/content/46/4/643.full.pdf+html

5Bhullar, K. et al. 2012. Antibiotic Resistance is Prevalent in an Isolated Cave Microbiome. PLoS One 7(4): 1-11.

6 Ropeik D. et al. (2002). RISK! A Practical Guide for Deciding What’s Really Safe and What’s Really Dangerous in the World Around You. Houghton Mifflin Company, Boston, 2002.

7 Hurd, H. S., et al. (2003). The Public Health Consequences of Macrolide Use in Food Animals: A Deterministic Risk Assessment. Journal of Food Protection, 67:5, 980-992.

8Hurd, HS, Yaegar MJ, Brudvig, JM, Taylor, DT, Wang, B. 2012. Lesion severity at processing as a predictor of Salmonella contamination of swine carcasses. American Journal of Veterinary Research 73(1):91-97.

9Hurd, HS, Brudvig, J, Dickson, J, Mirceta, J, Polovinski, M, Matthews, N, Griffith, R. 2008. Swine Health Impact on Carcass Contamination and Human Foodborne Risk. Public Health Reports. 123:343-351.

New CAST video released, "The Direct Relationship between Animal Health and Food Safety Outcomes."

The Council of Agricultural and Science Technology recently released a video entitled, "The Direct Relationship between Animal Health and Food Safety Outcomes." The video discusses how changing factors that affect animal health (including nutrition, welfare, housing systems, and antibiotic use) can have a significant impact on public health.

This video supplements the CAST paper released earlier this year. The video can be found at the link below:
http://www.youtube.com/watch?v=1SwsXURd2bU&feature=g-user-u

Organic versus conventional meat: is one better than the other?

Organic is no safer or better than conventional. This is the findings of a systematic review recently published by Stanford University looking at the topic of whether or not food raised organically is superior to food raised by conventional methods.(1) This publication is encouraging to see, as the authors examined hundreds of studies on the topic, not just on a few hand-picked studies. Meta analysis is a powerful objective method for analyzing a collection of conflicting evidence on a scientific topic.

Why is this organic question important? The organic market is seeing a massive increase in sales. According to the paper, the organic sales market went from $3.6 billion in 1997 to $26.7 billion in 2010.(2,3) The debate over organic food continues to heat up. The cost of organic food is usually 2 to three time more. But is it worth the extra cost?

The systematic review looked at two relevant points about how we might define “better”.

The first point is whether or not organic meat has less food-borne pathogens than conventionally raised meat. In analyzing the various studies, the authors did not find any significant difference in the amount of food-borne pathogens present. For example, in chicken 67% of organic samples were contaminated with Campylobacter versus 64% of conventional samples. Salmonella contamination was 35% for organic chicken versus 34% for conventional and E. coli contamination was 65% of organic samples versus 49% of conventional samples.(4)

The second point is whether or not there is antibiotic resistance bacteria present in organic meat, and if the amount of antibiotic resistant bacteria is lower in organic meat. All types of meat, including organic, have the potential to have antibiotic resistant bacteria.(5) While the review reported that conventionally raised chicken and pork are 33% more likely to have antibiotic resistance than organic meat, the findings weren’t statistically significant.1 This means that there is simply not enough data to prove the difference is more than chance. Also, just because meat has antibiotic resistant bacteria, does not mean that harm will necessarily result. A long chain of events must happen for human health harm to occur. First, the antibiotic resistant pathogens need to survive each processing step as well as cooking. Then the consumer needs to ingest the resistant bacteria, and have illness as a result that required antibiotic treatment. The harm would only result if all of these things happened and the bacteria did not respond to the antibiotic therapy.(6)

Bottom line, today’s modern farmer is not going to wipe out the human race. WHEW!


References
1Smith-Spangler, et al. 2012. Are Organic Food Safer or Healthier Than Conventional Alternatives?
Ann Intern Med 157:348-366.

2Dimitri, C. Oberholtzer L. 2009. Marketing U.S. Organic Foods: Recent Trends from Farms to Consumers. U.S. Department of Agriculture Economic Research Service, Economic Information Bulletin no. EIB-58.

3Organic Trade Association. 2010. U.S. Organic Industry values at nearly $29 billion in 2010.

4Miranda JM, et al. 2008. Antimicrobial resistance in Escherichia coli strains isolated from organic and conventional pork meat: a comparative survey. European Food Research and Technology. 226:371-5.

5Adams, J.U. 2012. Drug-Resistant Bugs found in Antibiotic-Free Meat. http://www.wired.com/wiredscience/2012/01/organic-meat-superbugs/

6Hurd, H.S. et al. 2004. Public Health Consequences of Macrolide Use in Food Animals: A Deterministic Risk Assessment. Journal of Food Protection. 67(5):980-992.

Wash your hands, there are resistomes in that dirt!

A remarkable paper by Forsberg et al. was just published in Science¹.  Using sophisticated “high-throughput” (fast and automatic) gene analysis techniques the authors demonstrated that soil contains antibiotic resistant bacteria and that resistance signals (messages, resistomes) are transmitted to other bacteria including types that make humans sick (pathogens). 

Now, I am not going to pretend to understand all the technical details of this elegant paper. However, I can understand that some may take this paper’s findings as “alarming”.  “The soil is awash with resistance, and it is due to antibiotic use in animals,” they may say.

However, as with all science, one paper’s findings must be compared and viewed in the greater body of knowledge.²  Also, when considering causation, timing is key. If we are creating this resistance pool, then there should be a time when little or no resistance existed. However, a few recent and also elegant papers show that antibiotics, as well as antibiotic resistance, have been around for a long, long time, way before people were using antibiotics, and maybe even before people walked the earth.  For example, Bhullar et al. found antibiotic multiple resistance in soil in a cave untouched for 4,000,000 years by mammalian life.³ Also, a study from D’Costa et al. found antibiotic resistance in 30,000 year old permafrost.⁴ Furthermore, another study states that a class of antibiotics called β-lactamases (which includes antibiotics such as penicillin), have been around for over 2 billion years, and even after decades of being used clinically, bacteria are still susceptible.⁵

I guess that is one more reason Mom made us wash our hands. However, it will be hard to explain to kids as they come screeching inside for dinner, “Wash your hands! That soil contains AB95 resistomes, DUDE!”

¹Forsberg, K.J. et al. 2012. The Shared Antibiotic Resistance of Soil Bacteria and Human Pathogens. Science 337:1107-1111

²Crombie, I.K, Davies, H.T. 2009. What is meta-analysis? Evidence-Based Medicine, 2^nd edition. pp. 1-8.
http://www.medicine.ox.ac.uk/bandolier/painres/download/whatis/meta-an.pdf

³Bhullar, K. et al. 2012. Antibiotic Resistance is Prevalent in an Isolated Cave Microbiome. PLoS One 7(4): 1-11.

⁴D’Costa, V. et al. 2011. Antibiotic Resistance is ancient. Nature 477:457-461http://www.nature.com/nature/journal/v477/n7365/full/nature10388.html

⁵Wright, G.D. 2007. The antibiotic resistome: the nexus of chemical and genetic diversity. Nature Reviews Microbiology 5:175-186. http://www.nature.com/nrmicro/journal/v5/n3/full/nrmicro1614.html

Antibiotics and Fat Babies

A recent report on NPR asks, "Could Antibiotics be a Factor in Childhood Obesity?" Another article on ABC News states, “Antibiotics too soon may set babies up for Obesity: Study.” 

I have to say these are about the funniest articles about antibiotics that I have seen in awhile. They are just laden with political implications! 

What is funny?

1.      Fortunately, the articles are clear that the evidence linking childhood obesity and antibiotic use is not strong.¹ NPR states, "Further studies are needed to confirm this trend." Of course, these articles refer to antibiotic treatment of the child, not animals. However, someone has already has made a connection to antibiotic use in food animals.^3,4

2.      For years some folks have been saying that antibiotic use in livestock does not really improve growth⁵ . However, these reports suggest even babies grow better with antibiotics⁶.  Additionally, the NPR article did cede that antibiotics in livestock may improve growth.

3.      Besides, what is wrong with a “fat” baby?  The article admits that the children showed no long term obesity problems, but that will likely be overlooked by the media.  Besides, what is what is wrong with a chubby bunny baby?  All of my children, except for one, looked like the old “Michelin Man”. Now they are perfect specimens of the human species (North European version).

4.      Sadly, like so many others, this article makes obesity someone else’s fault. It is the doctor who gave the antibiotics. Certainly, a baby cannot be expected to control its food consumption, but the parents can. Consumption is the key. It is not the food or antibiotics fault.

¹Barnett, S. 2012. Antibiotics too soon may set babies up for Obesity: Study. http://abcnews.go.com/Health/antibiotics-set-babies-obesity-study-suggests/story?id=17045227#.UDe3w6DNl7k

²Doucleff, M. 2012. Could Antibiotics Be a Factor in Childhood Obesity? http://www.npr.org/blogs/health/2012/08/22/159743999/could-antibiotics-be-a-factor-in-childhood-obesity

³The Huffington Post UK. 2012. Farmers may be causing Obesity Epidemic by Feeding Livestock Antibiotics. http://www.huffingtonpost.co.uk/2012/08/22/farmers-obesity-livestock-antibiotics-_n_1821941.html?utm_hp_ref=uk

⁴Collins, N. 2012.  Livestock Antibiotics ‘Could Have Contributed to Human Obesity.’ The Telegraph.
http://www.telegraph.co.uk/health/healthnews/9493178/Livestock-antibiotics-could-have-contributed-to-human-obesity.html

⁵Graham, JP et al. 2007. Growth Promoting Antibiotics in Food Animal Production: An Economic Analysis. Public Health Reports 122(1):79-87.

⁶Trasande, L et al. 2012. Infant Antibiotic Exposures and early life body mass. International
Journal of Obesity. http://www.nature.com/ijo/journal/vaop/ncurrent/full/ijo2012132a.html

           

 

New Campaign, “Meat without Drugs” could be inhumane!

As a public health veterinarian, I am concerned that a campaign such as “Meat without Drugs” could result in “Animals without Health”. A new report from Consumer Reports¹ provides some public opinion data that are not surprising. Given the constant drumbeat about the “overuse” of antibiotics in livestock production, consumers are frightened and convinced that there is a problem. One problem is that opinion polls and secret shopper surveys of labels are not scientific risk assessments. All peer-reviewed scientific risk assessments have demonstrated a negligible risk of human health harm due to livestock antibiotic use.^2,3,4

I think the bigger problem is that a campaign such as “Meat without Drugs” could mean that veterinarians have no way to treat sick animals or prevent epidemic diseases.  It is not possible to raise children without antibiotics. How do people expect us to raise these baby chicks, piglets and calves into wholesome meat, dairy and egg products without the assistance of modern medicine?  Actually, most of the antibiotics used on the farm are not the modern cutting edge products used by your local pediatrician.

Do the consumers and Consumer Reports know what happens to sick animals on organic farms, which produce animals without antibiotics? The veterinarian does not just give them some chamomile tea and send them to bed!  No, often they go untreated, hoping to get better. If that does not work then they may be treated (reluctantly) and then moved into a non-antibiotic-free group, maybe in the same barn. If they do shed some antibiotic resistant organisms, they are easily shared with their organic neighbors.  But the worst part is they may go UNTREATED. Once an ill animal is noted by the farmer, it has likely been sick for a while. There is little time left to treat before it dies. This waiting or denial of treatment is inhumane!

Data show that only about 13%⁵ of the total food-animal antibiotics used are for “growth promotion”. Very soon that amount will be zero, thanks to new guidance from the FDA⁶ . The remaining amounts are to prevent and treat painful deadly animal diseases. Does the consumer really want us to lose those tools that prevent animal suffering and improve food safety?

Some people say that raising animals in “crowded” conditions is the reason for needed antibiotic use. But pigs and kids can still get sick in any environment. Confinement housing is a means to provide protection from environmental extremes, predators, wildlife diseases, and stress; therefore reducing disease. Animal density is carefully monitored to provide optimal health.

Besides animal suffering, the impact of animal health on food safety and public health cannot be ignored. Healthy animals make safe food, and conversely  marginally healthy animals increase the risk of contamination from pathogens such as Campylobacter and Salmonella⁷ Additionally, a new report in Clinical Infectious Diseases showed an increased risk of Toxoplasmosis from organic livestock.⁸  Do you think Trader Joe’s or Whole Foods really want to sell more of these pathogens?

In summary, I think the choice of organically raised food products with clear labels is critical, and I am confident the USDA has and will continue to support accurate labeling. However, a problem in labeling should not put food safety, livestock health, and animal welfare at risk.

¹Consumer Reports. 2012. Meat on Drugs: The overuse of antibiotics in food animals and what supermarkets and consumers can do to stop it. Available online at: www.MeatWithoutDrugs.org
²Hurd, H.S. et al. 2004. Public Health Consequences of Marcolide Use in Food Animals: A Deterministic Risk Assessment. Journal of  Food Protection 67(5):980-992.
³Cox, L.A., Popken D.A. 2006. Quantifying potential human health impacts of animal antibiotic use: enrofloxacin and macrolides in chickens. Risk Analysis 26(1):135-146
⁴Anderson, S.A. et al. 2001. Assessment of the impact on human health of resistant Campylobacter jejuni from flouroquinolone use in beef cattle. Food Control 12(1):13-25.
⁵Animal Health Institute. 2012. Fact or Fiction: Common Antibiotic Myths. Available online at: http://www.ahi.org/issues-advocacy/animal-antibiotics/fact-or-fiction-common-antibiotic-myths/#2
⁶The Food and Drug Administration. 2012. Guidance for Industry #209: The Judicious Use of Medically Important Antimicrobial Drugs in Food Producing Animals. Available online at: http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM216936.pdf
⁷Coucil  for Agricultural Science and Technology. 2012. The Direct Relationship between Animal Health and Food Safety Outcomes. Available online at: http://www.cast-science.org/publications/?the_direct_relationship_between_animal_health_and_food_safety_outcomes&show=product&productID=155971
⁸Jones, J.L, Dubey, J.P. 2012. Foodborne Toxoplasmosis. Clinical Infectious Diseases. Epub ahead of print. 

Antibiotic use: Just how much is too much?

I recently read an article in Redbook¹ about the risk of antibiotic use in humans and animals; Not that I normally read Redbook. I never realized Redbook was such a political magazine. The article was aptly titled “Antibiotics are not candy.” It makes many good points about how human misuse may be contributing to the problem with antibiotic resistance in humans.  It also raises the valid concern about antibiotic usage in farm animals which may also be affecting antibiotic efficacy in humans. However, I need to point out a few potential untruths in the article.

1.  As terrible as Brody’s MRSA infection was, it was not from an animal type of MRSA. The type routinely cultured from pigs and poultry (ST398) rarely affects humans. The CDC has stated MRSA should not be considered as a foodborne illness.
2.  Other human disease examples noted in this article are not related to livestock, such as gonorrhea and carbapenem-resistant Enterobacteriaceae. (CRE). The association between chicken and urinary tract infections is scientifically very unproven.
3.  Another common resistant human infection, Vancomycin-resistant Enterococci (VRE), cannot not be blamed on vancomycin use in livestock.  Europe has the same rate of VRE as the US and we have never used, in animals, the vacomycin relative called avoparcin.
4.  The ideas shown in the compelling figure on page 151 have been evaluated in the multiple scientific peer reviewed papers and many confidential FDA required risk assessments. All that work has shown a negligible chance that the events would occur with frequency to harm the public health.

In regard to the article’s five (highly political) steps to fight super bugs, I would say:

1.  Use antibiotics correctly: Amen. The American Veterinary Medical Association and other practitioner groups have long promoted the prudent and judicious use of antibiotics.
2.  Buy meat labeled “raised without antibiotics” or “organic.”: If animals are raised without antibiotics, I wonder, “What happened to the ones got sick? Were they denied treatment so that farmer could get the premium price paid for antibiotic free?”
3.  Ask your favorite restaurants if they use meat raised without antibiotics: What does a veterinarian do for sick animals on a farm supplying Chipotle? Does this practice lead to animal welfare abuses?
4. Spread the message: Amen. We can all do better. I travel the world telling farmers and veterinarians to “put their antibiotic use house in order!”
5. Tell Congress to pass a law: NO.  As the article mentioned FDA has made a significant change in the way antibiotics will be used; spelling the end of growth promoting uses.  A law is too broad of a policy tool for this problem. It is like going after a mosquito with a bazooka.

I agree that resistant bacteria are an ongoing problem. But they have been for at least 4 million years.  Many types of resistant bugs were recently found in a cave in New Mexico, untouched by civilization.² (Also, resistant bacteria have been found in antibiotic-free meat, but that’s another topic for another blog.)³
 

¹Antibiotics are not candy. http://www.redbookmag.com/health-wellness/advice/how-antibiotics-cause-superbugs?click=main_sr

²Antibiotic Resistance Is Prevalent in an Isolated Cave Microbiome.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3324550/pdf/pone.0034953.pdf

³ Drug Resistant Bugs found in Antibiotic-Free meat. http://www.wired.com/wiredscience/2012/01/organic-meat-superbugs/