Does antibiotic use on concentrated feed animal operations negatively effect human health?

Drew Fournier, Bacherlor of Science in Natural Resource Conservation

Natalie Boisvert, Bachelor of Science Animal Science

Jim Shea, Bachelor of Science Turf Grass Science and Management

Kevin Calantone, Bachelor of Science in Building Construction Technology

 

An 11 year old perfectly healthy athletic girl named Addie suddenly became sick with a high grade fever and hip pain that refused to subside. Her mother promptly took her to the hospital where they diagnosed her with an antibiotic resistant staphylococcus infection (Pond, 2015). Within twenty-four hours of the diagnoses, she was being kept alive by machines and was declining by the hour (Pond, 2015). Doctors used every known antibiotic and drug to combat the vicious infection however, it was not enough. After suffering from a stroke Addie lost the capability to use her left arm and leg. She also lost vision in her left eye and nearly lost vision in her right eye in addition to losing ? of her body weight (Pond, 2015). This tragedy happened so fast that no one could have foreseen or cured the horrific illness. Addie is not the only victim to suffer from life threatening bacteria and for sure will not be the last.

Where did the bacteria that ultimately killed an 11 year old girl develop its resistance to antibiotics? Following the era of the world wars and the Great Depression, the agricultural industry was under extreme pressure to supply enough food for the American people (Imhoff, 2010). Simultaneously, farmers left their lands for the suburbs and cities which began to expand their industrialization into the luscious pastures of the countryside. To meet consumer demand with significantly less land and manpower, farmers moved animals indoors into confinement agriculture to control their environment and increase production efficiency (Imhoff, 2010). With this shift in production, small farms transformed into factory farms widely recognized as Concentrated Animal Feeding Operations (CAFOs). The U.S. Clean Water Act of 1972 classifies CAFOs as large facilities when they house 1000 cattle, 2500 swine, 10,00 sheep, or 30,000 laying hens (Centner, 2003, p. 433).

Because CAFOs house many animals in tight quarters, disease can spread quickly in livestock populations and have devastating effects on animal productivity. To prevent disease, farmers implemented non-therapeutic use of antibiotics within their production herds. Non-therapeutic use of antibiotics involves providing clinical doses in the feed over indefinite periods to enhance feed efficiency and promote faster growth (Paulson, 2015). The growth promotional benefits of low doses antibiotics is not fully understood, but scientists suggest that changes in the animal’s gut bacteria leads to beneficial changes in metabolism in which their ability to store fat increases (Paulson, 2015).  It is also thought that ensuring animals do not expend energy fighting off pathogenic bacteria optimizes their feed efficiency.  (Imhoff, 2010, p. 255-256).  When farmers apply continuous low doses of growth promoting antibiotics in the feed of CAFOs, they inadvertently select for drug resistant bacteria (Marshall & Levy, 2011 p.719).  Constantly clearing the environment of non-resistant bacteria creates an environment in which resistant strains no longer compete with dense bacterial populations and can grow quickly (Marshall & Levy, 2011 p.719).  This resulting imbalance creates a dense population of bacteria containing antibiotic resistant genes in the animal.  Condensing hundreds to thousands of animals into limited areas exacerbates the transmission of these resistant bacteria (Marshall & Levy, 2011 p.719).  The ultimate result of the overuse of antibiotics for growth promotion is a potent reservoir of antibiotic resistance bacteria hosted in the animals of CAFOs.

With that said, the U.S. faces a crisis in their tendency to use antibiotics non- therapeutically for production over therapeutically to combat disease.  Gruesome cases of ailments and sickness caused by food-borne diseases like those that maimed the 11-year-old girl Addie are only going to become more common as CAFOs become more numerous within our food economy (Gilchrist et al., 2007). As CAFOs become more common it’s natural that more people will find themselves living near CAFOs.  This idea is extremely worrying as there is a growing number of academic studies reporting that people who live near CAFOs run a higher risk of becoming sick from diseases such as bronchitis, mucus membrane irritation, asthma-like syndrome, and acute respiratory distress syndrome (Gibbs et al., 2006; Donham et al., 2006). Additionally, the degradation of water quality via CAFO wastewater runoff also poses a threat to human health as scientists continue to find antibiotic resistant bacteria in the drinking water supplies of municipalities where CAFOs are numerous (Burkholder et al., 2007).

It is clear then that this intermingling of commercially produced feed animals and humans poses a threat to human health (Ventola, 2015). In fact, an average of 2,000,000 people a year in the U.S. contract bacterial infections from hospitals alone and of those 2 million infected individuals, 90,000 of them die as a result of their ailment (Food and Drug Administration, 2004, p. 4). Reports show that 70% of those lethal infections are the result of bacterial strains containing antibiotic resistant genes for at least one drug (FDA, 2004 , p. 4). It is evident that there is substance in the idea that rising levels of antibiotic resistant bacteria within our ecosystem can lead to mass amounts of human disease, such as the MRSA bacterial infection that killed Addie. The spread of antibiotic resistance in bacteria is worrisome news for each and every person in the United States whether they live near to or far from a CAFO.  For this reason, we argue that congress must pass stringent laws that the FDA can use to ban non-therapeutic antibiotic use on CAFOs, as such use of antibiotics poses a public health threat by increasing the number of antibiotic resistant genes in bacterial populations.

Antibiotic resistant bacteria pose a more severe threat to human health than their non-resistant counterparts.  The Center for Disease Control and Prevention (2013) reaffirmed the severity of this public health concern by ranking the threat of 18 drug-resistant bacteria as either urgent, serious, or concerning (para 1) . The authors classified resistant E. Coli as a serious threat which causes 26,000 drug resistant infections and 1,700 deaths per year (CDC, 2013, para 7).  More concerning is Methicillin resistant Staphylococcus Aureus (MRSA) which causes 80,461 severe infections each year, 11,285 of which result in death (CDC, 2013, para 13) .  Non-resistant S. Aureus is a naturally occurring bacteria on our skin and in the rare instances that it causes infections, it presents itself as simple to treat boils and pimples (Pray, 2008).  When infections occur, Staphylococcus is easily treated with antibiotics (Pray, 2008). The story is not so simple when it comes to MRSA which requires a last resort antibiotic treatment of Vancomycin delivered directly into the bloodstream (Pray, 2008).  Even with available treatment options, patients with a MRSA surgical site infection have a 3.4x greater chance of death and spend 2x more on treatment compared to patients with infections caused by susceptible strains (Cosgrove, 2003, p. 58).  More alarming still is that in 2002, scientists found a strain of MRSA that was resistant to the last resort Vancomycin antibiotic treatment (Pray, 2008).

Besides the fact that antibiotic resistant bacteria limits the drugs you can effectively use to neutralize infection, their virulence or ability to cause disease is also increased.  A study by Roux et al. (2015) showed that acquisition of a certain antibiotic resistance gene not only conferred resistance to multiple classes of antibiotics, but it also increased the bacteria’s fitness (p. 5).  This resistance gene works by preventing the formation of an important protein that normally allows antibiotics to passing through the bacterial membrane and cause cell death (Roux, 2015, p. 1).  When researchers compared the virulence of mutant strains and wild type (non-resistant) strains, only 25% of the mutant infected mice survived after 24 hours of infection while 80% of the wild type infected mice survived (Roux 2015, p. 5).  It’s evident that mice infected with antibiotic resistant bacteria were less likely to survive showing that mutant strains have increased virulence.

The non-therapeutic use of antibiotics on CAFOs is leading to increasing numbers of bacteria carrying antibiotic resistant genes which ultimately poses a public health threat. For example, when testing ill poultry from CAFOs in Brazil, scientists found that antibiotic resistance to commonly applied poultry antibiotics remained significantly higher in 2013 than in the samples taken from 1987- 1991 (Penha Filho et al., 2016). The authors also found that resistance to commonly applied preventative antibiotics, which did not exist in poultry samples from the sampling period starting in 1987, did exist in the 2013 samples (Penha Filho et. al., 2016). These results shows that over time, prolonged periods of non-therapeutic antibiotic application causes resistance to increase in bacterial populations and for new antibiotic resistance to become prevalent. In another study, Philpott-Howard and Williams (1982) found that 15 out of 17 health centers in England saw a significant increase in antibiotic resistance to common antibiotics in bacterial samples between the years of 1977 and 1981 (p.1599). During this time period, total resistance to the antibiotic Ampicillin in the same 17 health clinics significantly increased from 1.6% to 6.6% of cases in four years (Philpott-Howard and Williams, 1982, p.1599).  Though this study is quite old for the standards of the quickly evolving field of antibiotic resistance studies, the data shows a clear increase in antibiotic resistance as the farms in the United Kingdom became more industrialized. The U.S. too can expect an increase in antibiotic resistance as our farms continue to focus more on scale of operation and less on safe production practices. It is clear from the scientific literature that the widespread use of non-therapeutically applied antibiotics results in an increased incidence of antibiotic resistance in bacterial populations.

Transmission of bacteria between humans and animals is widespread and when considering the increased danger of growing population of antibiotic resistant bacteria, this transmission poses a threat to human health. Multiple studies aligned in the identification of commonalities in antibiotic resistant bacteria isolated from humans and food animals.  One study showed 13% of reported illnesses from MDR salmonella strains occurred within 5 days of consuming poultry products outside of the home (Glynn et al. 2004, p. S229).  This suggests a direct relationship between the consumption of poultry products and contracting MDR salmonella showing transmission is prevalent. Additionally, scientists isolated an identical swine influenza virus in human and pig subjects that were environmentally exposed to each other at  U.S. County Fair (Killian 2012, p.S229).  Scientists sequenced eight genes isolated from bacterial samples of the infected swine and a child at the fair and found they were 100% identical (Killian 2012, p.S229).  In a study that compared Campylobacter isolated from humans and food producing animals in Japan, similarities were seen in the bacterial characteristics. The results confirmed the similarities when identical sequencing results showed that 73.1% of human isolates and 92.2% of poultry isolates were the same Campylobacter strain (Ishihara et al., 2006, p.158). This evidence further supports the notion that the transmission of disease causing pathogens between humans and food animals as a result of direct contact is not only possible but very common. When intertwining the issues of antibiotic resistance and bacterial transmission between humans and animals, developing antibiotic resistance on CAFO’s becomes a solidified problem.

The transmission of antibiotic resistant bacteria between humans and animals can also occur from indirect contact between the two parties. For example, the human consumption of contaminated drinking water facilitates the indirect transmission of antibiotic resistant bacteria between humans and infected animals (Burkholder et al., 2007). Antibiotic resistant bacteria from animal wastes can enter the environment from leakage of manure lagoons and major precipitation events, which results in overflow and runoff of animal waste utilized as crop fertilizer (Burkholder et al., 2007). Additionally, the amount of antibiotic resistant bacteria that enters drinking water supplies through these sources is significant because many bacteria can survive the anaerobic processing that the animal waste undergoes before becoming fertilizer (Burkholder et al., 2007).  As noted earlier in this paper, antibiotic resistant bacteria are extremely dangerous for human health as antibiotic resistant strains are more virulent than non-mutant strains (Cosgrove, 2003; Roux et al., 2015). It is evident then that the incidence of antibiotic resistant bacteria being found in human drinking water poses a human health threat.

For CAFO producers who may believe reducing the use of antibiotics will negatively affect production resulting in reduced profit margins, studies show that profit margins are not constrained by reduced production. On the contrary, farmers can save in other areas when they do not use antibiotics for growth promotion.  For example in a study from the World Health Organization, the authors concluded that both the poultry and swine industry offset the increased costs associated with phasing out of antibiotic growth promoters through not investing capital in antibiotics (Emborg et al., 2002).  There is also evidence that the ban of antibiotic growth promotion did not negatively affect the productivity (kg of broilers produced/m2 per grow out) or survivability rate in the broiler industry of Denmark (Emborg et al., 2002). Feed conversion (ie. total kg of feed used/total kg of live weight ), however, did increase by 0.1% from November 1995 to May 1999 (Emborg et al., 2002, p. 40). Additionally, feed efficiency (ie. pounds gained/kilogram of feed) went to highs of 1.83 immediately after the ban and to more than 1.84 in late 1999 (Emborg et al., 2002).  The ultimate result of banned growth promotional antibiotics in Denmark show that productivity is not lost rather it increases over time.

The U.S. government continues to exhibit a low level of urgency regarding the adoption of legislation to combat the serious public health threat of antibiotic resistance (Centner, 2003). In the year 2016, the U.S. still has yet to pass the legislation needed for the banning the use of antibiotics as a growth promoter. However countries within the EU, such as Denmark and Germany, banned non-specific antibiotic use in 1995 and 1996, respectively (Van den Bogaard, Bruinsma, & Stobberingh, 2000). The effect of the ban in Denmark is put into perspective when one looks at the difference in total amounts of antibiotics used in feed for food animals between 1994 and 2001. Before the ban in 1995, Denmark applied 205,686 kg of antibiotics to food animals whereas in 2001, they applied only 94,200 kg (Dibner & Richards, 2005, p. 635). This trend equates to a 54% decrease in the total amount of antibiotics used on feed animals during 7 years after the ban (Dibner and Richards, 2005, p. 635).  Another study showed that in only three years after the banning of antibiotics as a growth promoter, Denmark witnessed a decrease in one of their most common antibiotic resistant bacteria (VRE) in poultry from levels >80% in 1995 to <5% in 1998 (Bager, Aarestrup, Madsen & Wegner, 1999, p. 53). Similarly, Germany too witnessed a decrease in the incidence of VRE in their poultry from 100% in 1995 to 25% in 1997 following the ban of a growth promotional antibiotics (Klare, Badstübner, Konstabel, Böhme, Claus & White, 1999, p. 48). Additionally, in one German town the human carrier rate of antibiotic resistance to Avoparcin continually declined after the antibiotic ban, from rates of 13% in 1994 to 6.6% in 1996 and finally 4% in 1998 (Klare et al., 1999, p. 50). It is clear then that contrary to the inaction exhibited by the U.S., countries like Denmark and Germany continue to see decreases in infection by antibiotic resistant bacteria as a result of their proactive approach in outlawing the use of antibiotics as growth promoters. With that said, we advise that the U.S. consider the scientific evidence presented throughout this paper and use it to follow the lead of the many countries in the EU in passing stringent legislation that the FDA can use to more strictly regulate the use of antibiotics on CAFOs.

Non-therapeutic use of antibiotics on CAFO’s poses a threat to human health. This fact is evident from studies that show antibiotic resistant populations of bacteria are increasing in size (Seni et al., 2016, & Penha Filho et al. 2016), there is a high incidence of antibiotic resistant bacteria in wastewater (Brooks et al., 2014; Li et al., 2013), transmission of antibiotic bacteria between humans and infected animals is widespread (Glynn et al., 2004, Ishihara et al. 2006, & Killian et al., 2013), and antibiotic resistant bacteria are more virulent and cause difficult to treat infections (Ventola, 2015). If the practice of growth promotional antibiotic use continues, it is only a matter of time before antibiotics, once thought to be a miracle cure, become ineffective to super strains of resistant bacteria. Combating this issue is necessary and cost-effective, contrary to many parties who say that banning non-therapeutic use of antibiotics on CAFOs would infringe upon farm profit margins. We propose that congress pass legislation that forces the FDA to make stricter compliance guidelines for farmers who own CAFO’s and widely use antibiotics in a preventative manner.  It is evident that the U.S. needs to act on the matter of non-therapeutic use of antibiotics so that tragic stories like the death of 11 year-old Addie no longer plague our society.

References

Bager, F., Aarestrup, F. M., Madsen, M., & Wegener, H. C. (1999). Glycopeptide resistance in enterococcus faecium from broilers and pigs following discontinued use of avoparcin. Microbial Drug Resistance, 5(1), 53-56.

Brooks, J. P., Adeli, A., & McLaughlin, M. R. (2014). Microbial ecology, bacterial pathogens, and antibiotic resistant genes in swine manure wastewater as influenced by three swine management systems. Water Research, 57, 96-103. doi:http://dx.doi.org/10.1016/j.watres.2014.03.017

Burkholder, J., Libra, B., Weyer, P., Heathcote, S., Kolpin, D., Thorne, P. S., & Wichman, M. (2007). Impacts of waste from concentrated animal feeding operations on water quality. Environmental Health Perspectives, 115(2), 308–312. http://doi.org/10.1289/ehp.8839

Center for Disease Control and Prevention (2013). Antibiotic/antimicrobial resistance, biggest threats. Retrieved from: http://www.cdc.gov/drugresistance/biggest_threats.html

Centner, T. J. (2003). Regulating concentrated animal feeding operations to enhance the environment. Environmental Science & Policy, 6(5), 433-440. doi:http://dx.doi.org.silk.library.umass.edu/ 10.1016/S1462-9011(03)00071-6

Cosgrove S., Sakoulas G., Perencevich E., Schwaber M., Karchmer A., & Carmeli Y. (2003). Comparison of mortality associated with methicillin?resistant and methicillin?susceptible staphylococcus aureus bacteremia: a meta?analysis. Clinical Infectious Diseases,?36, 53?59.

Dibner, J. J., & Richards, J. D. (2005). Antibiotic growth promoters in agriculture: History and mode of action. Poultry Science, 84(4), 634-643.

Donham, K. J., Wing, S., Osterberg, D., Flora, J. L., Hodne, C., Thu, K. M., & Thorne, P. S. (2007). Community health and socioeconomic issues surrounding concentrated animal feeding operations. Environmental Health Perspectives, 115(2), 317-320.

Emborg, H. D., Ersboll, A. K., Heuer, O. E. & H. C. Wegener. (2002). Effects of termination of antimicrobial growth promoter use for broiler health and productivity. Poultry Science 95(4),

38–42

Food and Drug Administration (2004). Bad bugs, no drugs: as antibiotic discovery stagnates, a public health crisis brews. Infectious Disease Society of America,1-37.

Gibbs, S. G., Green, C. F., Tarwater, P. M., Mota, L. C., Mena, K. D., & Scarpino, P. V. (2006). Isolation of antibiotic-resistant bacteria from the air plume downwind of a swine confined or concentrated animal feeding operation. Environmental Health Perspectives, 114(7), 1032-1037.

doi:10.1289/ehp.8910

Gilchrist, M. J., Greko, C., Wallinga, D. B., Beran, G. W., Riley, D. G., & Thorne, P. S. (2007). The potential role of concentrated animal feeding operations in infectious disease epidemics and antibiotic resistance. Environmental Health Perspectives, 115(2), 313-316.

Glynn, M. K., Reddy, V., Hutwagner, L., Rabatsky-Ehr, T., Shiferaw, B., Vugia, D. J…& Angulo, F. J., (2004). Prior antimicrobial agent use increases the risk of sporadic infections with multidrug- resistant salmonella enterica Serotype typhimurium: a FoodNet case-control study, 1996–1997. Cid, 38(3), S227-S236. doi:10.1086/381591

Imhoff, D. (2010). The CAFO reader: The tragedy of industrial animal factories. Healdsburg, California.: Watershed Media.

Ishihara, K., Yamamoto, T., Satake, S., Takayama, S., Kubota, S., Negishi, H., . . . Tamura, Y. (2006). Comparison of campylobacter isolated from humans and food-producing animals in japan. Journal of Applied Microbiology, 100(1), 153-160. doi:10.1111/j.1365-2672.2005.02769.x:

Killian, M. L., Swenson, S. L., Vincent, A.L., Landgraf, J.G., Shu, B., Lindstrom, S., Xu, X., Klimov, A., Zhang, Y., Bowman, A.S. (2012). Simultaneous infection of pigs and people with triple- reassortant swine influenza virus H1N1 at a U.S. county fair. Zoonoses and Public Health, 60, 196-201. doi: 10.1111/j.1863-2378.2012.01508.x

Klare, I., Badstübner, D., Konstabel, C., Böhme, G., Claus, H., & Witte, W. (1999). Decreased incidence of VanA-type vancomycin-resistant enterococci isolated from poultry meat and from fecal samples of humans in the community after discontinuation of avoparcin usage in animal husbandry. Microbial Drug Resistance, 5(1), 45-52.

Li, Y.-x., Zhang, X.-l., Lu, X.-f., Liu, B., Wang, J., & Li, W. (2012). The residues and environmental risks of multiple veterinary antibiotics in animal faeces. Environmental Monitoring and Assessment, 185(3), 2211-2220. doi:10.1007/s10661-012-2702-1

Marshall, B. M. & Levy, S. B. (2011). Food animals and antimicrobials: impacts on human health. Clinical Microbiology Reviews, 24(4), 718–733. http://doi.org/10.1128/CMR.00002-1

Paulson, J. A. (2015). Nontherapeutic use of antimicrobial agents in animal agriculture: implications for pediatrics. Pediatrics, 136(6), e1670-e1674. Retrieved from: http://pediatrics.aappublications.org/ content/early/2015/11/11/peds.2015-3630

Penha Filho, R.,Antonio Casarin, Ferreira, J. C., Iba Kanashiro, A. M., da Costa Darini, C. D., & Junior, A. B. (2016). Antimicrobial susceptibility of salmonella gallinarum and salmonella pullorum isolated from ill poultry in brazil. Ciência Rural, 46(3), 513-518.

doi:10.1590/0103-8478cr20150398

Philpott-Howard, J., & Williams, J. D. (1982). Increase in antibiotic resistance in haemophilus influenzae in the united kingdom since 1977: Report of study group. British Medical Journal (Clinical Research Ed.), 284(6329), 1597-1599.

Pond, Greg. (2015). A profile in courage: 11-year-old Addie Rerecich. MRSAidblog. Retrieved from: http://www.mrsaidblog.com/2015/06/09/a-profile-in-courage-11-year-old-addie-rerecich-2/

Pray, L. (2008) Antibiotic resistance, mutation rates and MRSA. Nature Education 1(1):30. Retrieved from: https://owl.english.purdue.edu/owl/resource/560/10/

Roux D. et al (2015).  Fitness cost of antibiotic susceptibility during bacterial infection. Science Translational Medicine, 7(297), 1-11. doi: 10.1126/scitranslmed.aab1621.

Seni, J., Falgenhauer, L., Simeo, N., Mirambo, M. M., Imirzalioglu, C., Matee, M., … Mshana, S. E. (2016). Multiple ESBL-producing escherichia coli sequence types carrying quinolone and aminoglycoside resistance genes circulating in companion and domestic farm animals in Mwanza, Tanzania, harbor commonly occurring plasmids. Frontiers in Microbiology, 7(142), 3-7 http://doi.org/10.3389/fmicb.2016.00142

Van den Bogaard, A.E., Bruinsma, N., & Stobberingh, E.E. (2000). The effect of banning Avoparcin on VRE carriage in the Netherlands. J. Antimicrob Chemother. 46(1): 146-148. doi: 10.1093/jac/ 46.1.146

Ventola, C. L. (2015). The antibiotic resistance crisis: part 1: causes and threats. Pharmacy and Therapeutics, 40(4), 277–283.

Wegener, H. C. (2003). Antibiotics in animal feed and their role in resistance development. Current Opinion in Microbiology, 6(5), 439-445. doi:http://dx.doi.org/10.1016/j.mib.2003.09.009

Zhang, Y., Bowman, A.S. (2012). Simultaneous infection of pigs and people with triple-reassortant swine influenza virus H1N1 at a U.S. county fair. Zoonoses and Public Health, 60, 196-201. doi: 10.1111/j.1863-2378.2012.01508.x

Evan