Abstract
Debate over how regulation can address the growing public health crisis of antimicrobial resistance has addressed both the regulatory framework for intervention and the political choice to intervene, balancing control of the public health risk from agricultural use of antimicrobials and economic benefit to agribusiness from such use. This chapter reviews current U.S. laws and regulations pertaining to non-therapeutic use of antimicrobials in livestock and to surveillance of antimicrobial-resistant pathogens of food animal origin. Regulatory efforts in the United States and Europe are compared, with an emphasis on the scientific evidence for public health success or failure of these policy interventions. The chapter also provides the scientific context that informs regulatory efforts in the U.S. and global efforts to address the problem of antimicrobial resistance. Recommendations for combined regulatory, surveillance, and research strategies are offered, with a focus on science-based regulatory approaches and mechanisms for evaluation of the public health benefits of regulation.
A version of this chapter was originally published in Volume 25 of the Tulane Environmental Law Journal 2011–2012.
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- 1.
Kastner et al. (2012), pp. 6868–6872.
- 2.
Silbergeld et al. (2008a).
- 3.
- 4.
Food-producing animals, also known as livestock or food animals, include all animals raised for meat, milk, or eggs for human consumption. Pigs, poultry (“layer” chickens which produce eggs, “broiler” chickens raised for meat, and turkeys), dairy cows, beef cattle, and farmed fish (e.g., catfish) are examples of the most common food-producing animals raised in the United States. See U.S. Dep’t Agric., Census of Agriculture (2007), available at http://www.agcensus.usda.gov/Publications/2007/Full_Report/usv1.pdf.
- 5.
In this chapter, the terms “antimicrobial” and “antibiotic” may occasionally appear to be used interchangeably, as antibiotics are, by some definitions, considered to be antimicrobials. Not all antimicrobials are antibiotics, however. Some regulations may apply to all antimicrobials broadly (used to treat infections with viruses, bacteria, parasites, and fungal organisms), and others to drugs used to treat bacterial infections specifically. Technically, the term antibiotic refers only to chemicals naturally produced by microorganisms that kill or impair other microorganisms; otherwise, synthetic “antibiotics” are considered antimicrobials. For a lay definition of these terms, see Ctrs. for Disease Control & Prevention, Antibiotic/Antimicrobial Resistance, www.cdc.gov/drugresistance/index.html (last visited Sept. 13, 2011). See also Luca Guardabassi & Patrice Courvalin, Modes of Antimicrobial Action and Mechanisms of Bacterial Resistance, in Antimicrobial Resistance in Bacteria of Animal Origin 1, 1 (Frank M. Aarestrup ed., 2006) (concerning use and misuse of the terms antimicrobial and antibiotic).
- 6.
Peter Lees et al., Drug Selection and Optimization of Dosage Schedules to Minimize Antimicrobial Resistance, in Antimicrobial Resistance in Bacteria of Animal Origin, (Frank M. Aarestrup ed., 2006), at 49.
- 7.
Van Boeckel et al. (2014), pp. 742–750.
- 8.
Id. at 49.
- 9.
Am. Soc’y Microbiology, Report of the ASM Task Force on Antibiotic Resistance (1995), available at http://www.asm.org/images/docfilename/0000005962/antibiot[1].pdf; Oguz Resat Sipahi (2008), pp. 523–526.
- 10.
Am. Soc’y Microbiology, (1995), at 3.
- 11.
Coast and Smith (2003), pp. 241–242.
- 12.
Sipahi (2008), p. 526.
- 13.
Antimicrobial Resistance in Bacteria of Animal Origin, (Frank M. Aarestrup ed., 2006), at 26 (adapted from Alan H. Linton, Antibiotic Resistance: The Present Situation Reviewed, 100 Veterinary Rec. 354 (1977) and modified by R. Irwin from a model sometimes referred to as the “confusogram”).
- 14.
- 15.
Prescott (2006), p. 22.
- 16.
The practice of feeding antimicrobials at levels below that which treat clinical infection, alternately termed “non-therapeutic” or “sub-therapeutic” use, originated in the late 1940s and early 1950s. During that era, this use was shown to hasten animal weight gain and, at times, reduce mortality in herds or flocks. In the United States, “subtherapeutic levels” sometimes are defined as concentrations of antimicrobials that are less than 200 g per ton of feed. The degree to which this use remains an economic incentive for an individual farmer or industrial producer depends on many factors, including the underlying health and environmental living conditions of the animals. See id. at 19–23.
- 17.
Antimicrobial drugs differ in their ability to kill (bacteriocidal drugs) or inhibit (bacteriostatic drugs) different kinds of bacteria. For example, fluoroquinolone drugs (e.g., ciprofloxacin and enrofloxacin) are broad-spectrum and are active against gram-negative bacteria (e.g., E. coli) and gram-positive cocci (e.g., Staphylococcus aureus), but have only weak activity against anaerobic bacteria (e.g., Clostridium).
- 18.
Prescott (2006), pp. 22–23.
- 19.
- 20.
Margaret Mellon et al., Hogging It!: Estimates of Antimicrobial Abuse in Livestock xiii (2001).
- 21.
This is the fourth report on such uses produced in response to requirements of the Center for Veterinary Medicine of the FDA under § 512 of the Animal Drug User Fee Amendments of 2008 (ADUFA) 21 U.S.C. § 360b(l) (2009). This estimate includes all uses in food-producing animals for all purposes (growth promotion, prophylaxis, or therapy), and regardless of route of administration (via injection, oral administration, or in medicated feed). See Ctr for Veterinary Med., U.S. Food and Drug Administration, 2012. Summary Report on Antimicrobials Sold or Distributed for Use in Food-Producing Animals (2014), available at http://www.fda.gov/downloads/ForIndustry/UserFees/AnimalDrugUserFeeActADUFA/UCM416983.pdf.
- 22.
Letter from Karen Meister, Supervisory Congressional Affairs Specialist, Food and Drug Administration, to Rep. Louise A. Slaughter, U.S. House of Representatives (Apr. 19, 2011), available at http://www.louise.house.gov/images/stories/FDA_Response_to_Rep._Slaughter.pdf.
- 23.
OTC drugs are sold or dispensed without requirement for human or veterinary prescription; Ctr for Veterinary Med., U.S. Food and Drug Administration, 2012, at 5.
- 24.
World Health Org., The Medical Impact of Antimicrobial Use in Food Animals (1997), available at http://whqlibdoc.who.int/hq/1997/WHO_EMC_ZOO_97.4.pdf.
- 25.
Two criteria were used by WHO to determine the importance of antibiotics that may be used in food-producing animal production for human health. The first criterion was the importance of the drug in human health, i.e., whether or not the drug was the only or one of few available to treat a given disease. The second criterion was the use of a given antibiotic to treat specifically zoonotic disease, i.e., a disease that can be transmitted from an animal to a human. These were given higher weight. See World Health Org., Critically Important Antibacterial Agents for Human Medicine for Risk Management Strategies of Non-Human Use 4–5 (2005), available at www.who.int/foodborne_disease/resistance/amr_feb2005.pdf.
- 26.
World Health Org., Critically Important Antibacterial Agents, (2005).
- 27.
Aarestrup et al. (2001), p. 2054.
- 28.
Emborg and Wegener (2005), pp. 168–169.
- 29.
Id. at 163–67.
- 30.
- 31.
Am. Soc’y Microbiology, (1995), pp. 7–8; John G. Bartlett et al., Statement of the Infectious Diseases Society of America before the Food and Drug Administration Part 15 Hearing Panel on Antimicrobial Resistance (2008), available at http://www.idsociety.org/uploadedFiles/IDSA/Policy_and_Advocacy/Current_Topics_and_Issues/Advancing_Product_Research_and_Development/Antimicrobials/Statements/ee434daf62ba4fedac689288741635704.pdf#search=%22Statement of the Infectious Diseases Society of America before the Food Drug Administration Part 15 Hearing Panel on Antimicrobial Resistance%22.
- 32.
Pew Comm’n Indus. Food Animal Prod., Putting Meat on the Table: Industrial Farm Animal Production in America 15–16 (2008), available at http://www.pewtrusts.org/uploadedFiles/wwwpewtrustsorg/Reports/Industrial_Agriculture/PCIFAP_FINAL.pdf; Mellon et al., 17.
- 33.
U.S. Gen. Accounting Office, Antibiotic Resistance: Federal Agencies Need to Better Focus Efforts to Address Risk to Humans from Antibiotic Use in Animals (2004), available at www.gao.gov/cgi-bin/getrpt?GAO-04-490.
- 34.
U.S. Food & Drug Admin., Guidance for Industry #152 – Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to Their Microbiological Effects on Bacteria of Human Health Concern (2003), available at www.fda.gov/cvm/guidance/fguide152.pdf; Guidance for Industry #209 – The Judicious Use of Medically-Important Antimicrobial Drugs in Food-Producing Animals (2012), available at http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM216936.pdf; U.S. Food & Drug Admin., Guidance for Industry #213 - New Animal Drugs and New Animal Drug Combination Products Administered in or on Medicated Feed or Drinking Water of Food- Producing Animals: Recommendations for Drug Sponsors for Voluntarily Aligning Product Use Conditions with GFI #209 (2013), available at http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM299624.pdf.
- 35.
Donald Kennedy, Cows on Drugs, N.Y. Times, Apr. 18, 2010, at WK11; Preservation of Antibiotics for Medical Treatment Act of 2009: Hearing before the H. Comm. on Rules, 111th Cong. (2009) (statement of Joshua Sharfstein, Principal Deputy Comm’r, U.S. Food and Drug Admin.).
- 36.
Kennedy, (2010); Animal Health Inst., Political Bans on Antibiotics are Counterproductive: European Test Case: Increased Animal Disease, Mixed Human Health Benefit (2006), available at www.ahi.org/content.asp?contentid=715; Am. Veterinary Med. Ass’n, 111th Congress Legislative Agenda: H.R. 1549/S. 619 Preservation of Antibiotics for Medical Treatment Act -- Active Pursuit of Defeat (2010), available at http://www.avma.org/advocacy/avma_advocate/apr10/aa_apr10_all.asp; Eric Gonder, Letter to the Editor, Poultry Veterinarians’ Perspectives on Antimicrobial Resistance, 237 J. Am. Veterinary Med. Ass’n 258 (2010); Becky Tilly, Letter to the Editor, Poultry Veterinarians’ Perspectives on Antimicrobial Resistance, 237 J. Am. Veterinary Med. Ass’n 258 (2010).
- 37.
Laxminarayan et al. (2013), pp. 1057–1098.
- 38.
Baltz (2008), p. 557.
- 39.
Forrest (1982), pp. 198–200 (describing uses of copper, mercury, honey, and resins).
- 40.
Keyes et al. (2003), pp. 45–46.
- 41.
Id. at 45–46.
- 42.
Vanessa M. D’Costa et al., Antibiotic Resistance is Ancient, Nature, (accessed ahead-of-print, August 31, 2011).
- 43.
Keyes et al. (2003), pp. 45–46.
- 44.
Guardabassi and Courvalin (2006) pp. 1–18.
- 45.
Id. pp. 8–12.
- 46.
Mechanisms of resistance vary among bacteria according to the specific antibiotic or class of antimicrobials under consideration. For example, the mecA gene in Staphylococcus aureus, making this pathogen methicillin-resistant (MRSA), alters a target protein normally used by the class of penicillin drugs (including methicillin) to inhibit cell wall synthesis. This altered protein, PBP2a, does not bind well to penicillin drugs, and thus MRSA evades penicillin attack. See id.
- 47.
Wright (2007), pp. 175, 183–184.
- 48.
Keyes et al. (2003), p. 51.
- 49.
This typically occurs on a mobile genetic element (e.g., plasmid), which is a piece of genetic material capable of being transferred between bacteria, usually via a process called bacterial conjugation. See Andremont (2000), p. S178.
- 50.
Ito et al. (2003), pp. 41–49.
- 51.
Id. at 49.
- 52.
Wright (2007), pp. 175–186.
- 53.
Dethlefsen et al. (2007), pp. 811–812.
- 54.
Davis et al. (2011), pp. 244–245.
- 55.
Loreau (2010), pp. 49–55.
- 56.
Davis et al. (2011), pp. 244–245.
- 57.
Turnbaugh et al. (2007), p. 804.
- 58.
Davis et al. (2011), pp. 244–245.
- 59.
Wright (2007), p. 176.
- 60.
Id.
- 61.
Multiplication of resistance genes may occur through expansion of resistant populations of bacteria (one resistant bacterium becomes two, etc.), and also through horizontal gene transfer, in which the plasmid that contains the gene itself is copied and shared with a formerly susceptible bacterium.
- 62.
Wright (2007) 49, p. 176.
- 63.
Davis et al., An Ecological Perspective, (2011), at 256; Skippington and Ragan (2011), p. 707.
- 64.
Lee et al. (2010), p. 82.
- 65.
Silbergeld et al. (2008b), pp. 1391–1392.
- 66.
- 67.
Dellit et al. (2007), p. 159; Ctrs. Disease Control & Prevention, Get Smart: Know When Antibiotics Work, (2011), available at www.cdc.gov/getsmart/index.html.
- 68.
Dellit et al. (2007), pp. 159–160.
- 69.
Pets, or companion animals, include dogs, cats, horses, rabbits, and other animals that might be kept in or near the household.
- 70.
Am. Veterinary Med. Ass’n, AVMA Guidelines for Judicious Therapeutic Use of Antimicrobials (2010), available at http://www.avma.org/issues/jtua/jtua_poultry.asp.
- 71.
Id.
- 72.
Radostits et al. (1985).
- 73.
Parenteral use (injection) is common for disease treatment except some uses in poultry production and aquaculture due to difficulty of injection or the muscle damage an injection could cause in these smaller species. See id. at 85.
- 74.
Ctr for Veterinary Med., Summary Report, (2012).
- 75.
Love et al. (2011a), p. 279.
- 76.
In addition to medication of animals, antimicrobials also may be used in agricultural environments, in environmental sanitation, and crop treatment; these latter uses are regulated by the Environmental Protection Agency. See U.S. Envtl. Prot. Agency, Pesticide Registration Manual: Chapter 18 - Other Federal or State Agency Requirements (2010), available at www.epa.gov/pesticides/bluebook/chapter18.html#antimicrobial.
- 77.
- 78.
Elmund et al. (1971), pp. 129–131.
- 79.
Davis et al. (2011), pp. 246–248.
- 80.
Love et al. (2011a), p. 279.
- 81.
- 82.
CAFOs, otherwise known as industrial food animal production facilities, are typified by high-throughput methods designed to achieve a uniform product (meat, milk, or eggs) in a standardized period of time to accommodate mechanized harvest methods. High animal density, waste (manure) concentration, and use of antimicrobials, often in medicated feed, are hallmarks of these systems. See Davis et al. (2011), pp. 244–245; Love et al. (2011a), p. 279; Silbergeld et al. (2008a), p. 123.
- 83.
Silbergeld et al. (2008a), p. 123.
- 84.
Martinez (2009), p. 2893.
- 85.
- 86.
U.S. Food and Drug Administration, NARMS 2008 Executive Report 1–3 (2009), available at http://www.fda.gov/downloads/AnimalVeterinary/SafetyHealth/AntimicrobialResistance/NationalAntimicrobialResistanceMonitoringSystem/UCM253024.pdf; McEwen and Fedorka-Cray (2002), pp. S99–S101.
- 87.
Love et al. (2011b), p. 7232.
- 88.
David C. Love et al., Poultry Feather Meal from the United States and China Contains Residues of Multiple Pharmaceuticals and Personal Care Products (PPCPs). (2012; on file with author).
- 89.
- 90.
U.S. Food and Drug Admin., NARMS 2008, (2009); McEwen et al. (2010), pp. 561–562. Effects from use of fluoroquinolones, virginiamycin, and other drugs will be discussed, infra.
- 91.
- 92.
Of note, the finding of an association between use of cephalosporins, including ceftiofur, in food-producing animals and cephalosporin resistance in human isolates was the basis for an attempt by the FDA to restrict extra-label use of these antimicrobials in food-producing animals. New Animal Drugs; Cephalosporin Drugs; Extralabel Animal Drug Use; Order of Prohibition, 73 Fed. Reg. 38,110–38,113 (July 3, 2008) (to be codified at 21 C.F.R. pt. 530). The initial order was revoked before it took effect. See U.S. Food & Drug Admin., FDA Revokes Order Prohibiting Extra-label Use of Cephalosporin (2008), available at www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm054431.htm. A new order to prohibit certain extra-label uses of certain cephalosporins was published in early 2012. New Animal Drugs; Cephalosporin Drugs; Extralabel Animal Drug Use; Order of Prohibition, 77 Fed. Reg. 4,735–745 (January 6, 2012) (to be codified at 21 C.F.R. pt. 530). Extra-label use by veterinarians is use in a species or at a dosage or via a route not specifically included in the approval (label) of that animal drug. The Animal Medicinal Drug Use Clarification Act (AMDUCA) of 1994, as implemented by FDA regulation (21 C.F.R. § 530), authorizes the veterinarian to prescribe an animal drug for extra-label use under certain conditions. This extra-label use is, in part, a response to the many species veterinarians need to treat which may not have specifically been tested during the drug approval process.
- 93.
U.S. Food & Drug Admin., National Antimicrobial Resistance Monitoring System - Enteric Bacteria: 2004, Human Isolates Final Report (2004), available at http://www.cdc.gov/narms/annual/2004/NARMSAnnualReport2004.pdf.
- 94.
FDA’s Role in Antimicrobial Resistance: Hearing Before the Subcomm. on Livestock, Dairy, and Poultry of the H. Comm. On Agriculture, 110th Cong. (2008) (statement of Bernadette Dunham, Director, Ctr. Veterinary Med.).
- 95.
Even vegetarians and vegans may be impacted by zoonotic bacteria through the food they eat, because vegetables may be contaminated by water or dust containing bacteria of food animal origin. Examples include E. coli 0157:H7 outbreaks traced to animal manure spread in apple orchards and irrigation water for spinach crops. See Gerba and Smith (2005), p. 42.
- 96.
Sherris and Florey (1951), p. 309.
- 97.
Kiser, p. 1058.
- 98.
England’s Netherthorpe Committee was established in response to a 1955 meeting of the Agricultural Research Institute of the National Academy of Sciences (NAS) held on October 17–18 in Washington, D.C. in which, although resistance in animal microbes to in-feed antimicrobials was found, a conclusion of no hazard to human health was made. Id.
- 99.
Id.
- 100.
Id. at 1058–1059.
- 101.
Id. at 1059–1060.
- 102.
Soulsby (2007), p. i77; House of Lords, Use Of Antibiotics In Animal Husbandry And Veterinary Medicine (Swann Report) (1969), http://hansard.millbanksystems.com/commons/1969/nov/20/use-of-antibiotics-in-animal-husbandry.
- 103.
Id. at i77.
- 104.
Id. at i78 (concerning UK involvement).
- 105.
The Alliance for the Prudent Use of Antibiotics (APUA) is an international advocacy organization based at Tufts University in the United States and sponsors the ROAR network of scientists. Alliance for the Prudent Use of Antibiotics, available at http://www.tufts.edu/med/apua/about_us/what_we_do.shtml (last visited Nov. 21, 2011).
- 106.
Soulsby (2007), p. i78.
- 107.
Reservoirs of Antibiotic Resistance, available at http://www.roarproject.org/ROAR/html/index.htm (last visited Nov. 21, 2011) (describing research activities and U.S. funding mechanisms); Soulsby (2007), p. i78 (concerning UK involvement).
- 108.
At the time, the World Organisation [sic] for Animal Health was called the Office International des Epizooties (OIE). The OIE is a global reference body, headquartered in Paris with 178 member countries, dedicated to international cooperation to combat animal diseases. The United States is a member of this 80-year old world organization.
- 109.
Id.
- 110.
Id.
- 111.
Interagency Task Force on Antimicrobial Resistance, A Public Health Action Plan, 2011 Revision, 130, at 15.
- 112.
Centner, at 6–7.
- 113.
Falkow and Kennedy (2001), p. 397.
- 114.
21 C.F.R. §§ 520, 522, 556 (2001); 21 C.F.R. §§ 520, 556 (2005) (concerning the withdrawal of FDA approval for uses in poultry of veterinary fluoroquinolones).
- 115.
42 U.S.C. § 247d-5 (2011).
- 116.
21 C.F.R. §§ 520, 556.
- 117.
U.S. Food & Drug Admin., Guidance for Industry #152, (2003).
- 118.
U.S. Food and Drug Administration, NARMS 2008, (2009), at 2.
- 119.
Monnet (2000), p. 91.
- 120.
See supra.
- 121.
Geocoding is a technique for converting an address into a point on a map on the basis of latitude and longitude. Researchers can use this information to conduct spatial data analysis comparing sources of antimicrobial contamination with patterns of resistance in human, animal, and environmental bacteria. See Beth Feingold et al., Spatial Analysis of Livestock Associated MRSA, (conference abstract) Ass’n Am. Geographers (conf. abstract, Apr. 13, 2011), available at http://meridian.aag.org/callforpapers/program/AbstractDetail.cfm?AbstractID=39548.
- 122.
Danish Integrated Antimicrobial Resistance Monitoring and Research Program.
- 123.
Andreasen et al., at 41–42.
- 124.
JMI Laboratories: Surveillance, available at http://www.jmilabs.com/surveillance/ (last visited Nov. 21, 2011).
- 125.
Euro. Food Safety Auth., About EFSA, www.efsa.europa.eu/en/aboutefsa.htm (last visited Sept. 17, 2011).
- 126.
Euro. Ctr. Disease Prevention & Control, Mission, www.ecdc.europa.eu/en/aboutus/Mission/Pages/Mission.aspx (last visited Sept. 17, 2011).
- 127.
Council Directive 2003/99/EC, available at http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2003:325:0031:0040:EN:PDF.
- 128.
de Jong et al. (2009), p. 733.
- 129.
Id. (noting that few resistance patterns following the bans returned to zero, and also that some resistance patterns (e.g., to streptogramins and fluoroquinolones) remain higher than expected); see infra.
- 130.
- 131.
FDA’s Role in Antimicrobial Resistance: Hearing, (2008) (statement of Bernadette Dunham).
- 132.
USDA/HHS Response to the House and Senate Reports: Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations Bill 1 (2000), available at http://www.fda.gov/downloads/AnimalVeterinary/SafetyHealth/AntimicrobialResistance/UCM134733.pdf.
- 133.
Salmonella spp. and Campylobacter jejuni are human enteric pathogens, while Enterococcus and E. coli may be present commensally or may cause disease opportunistically.
- 134.
The antimicrobials are: Azithromycin, Ciprofloxacin, Clindamycin, Erythromycin, Florfenicol, Gentamicin, Nalidixic Acid, Telithromycin, and Tetracycline.
- 135.
FoodNet was launched with five states, and additional states were added slowly through a state application/selection process. The current FoodNet states are Connecticut, Georgia, Maryland, Minnesota, New Mexico, Oregon, Pennsylvania, Tennessee, California (selected counties), Colorado (selected counties), and New York (selected counties). See Samantha Yang, FoodNet and Enter-net: Emerging Surveillance Programs for Foodborne Diseases, 4 Emerging Infectious Diseases 457 (1998); Ctrs. for Disease Control & Prevention, FoodNet – Foodborne Diseases Active Surveillance Network, http://www.cdc.gov/foodnet/ (last visited Sept. 15, 2011).
- 136.
U.S. Food & Drug Admin., NARMS Program (2010), http://www.fda.gov/AnimalVeterinary/SafetyHealth/AntimicrobialResistance/NationalAntimicrobialResistanceMonitoringSystem/ucm059089.htm.
- 137.
Id.
- 138.
Sorensen et al. (2014), p. 2.
- 139.
IDSA (2012).
- 140.
Interagency Task Force on Antimicrobial Resistance, Progress Report: Implementation of a Public Health Action Plan to Combat Antimicrobial Resistance, Progress Through 2007 3 (2008), available at http://www.cdc.gov/drugresistance/actionplan/2007_report/ann_rept.pdf.
- 141.
Witte (2000), p. S19.
- 142.
- 143.
The countries are: Belgium, Denmark, Finland, France, Germany, Great Britain, the Netherlands, and Norway. Wegener et al. (1999), pp. 329–331.
- 144.
Sweden banned all growth promoters in 1986, and avoparcin was not approved as a growth promoter in the United States due to concerns about carcinogenicity. See Wegener et al. (1999), pp. 330–331.
- 145.
Witte (2000), pp. S19–S20.
- 146.
Id.; Aarestrup et al., Associations Between the Use of Antimicrobial Agents, (2000), pp. 68–69.
- 147.
Synercid®, also known as quinupristin/dalfopristin, was the first streptogramin drug widely released for human use, but its final approval in 1999 came decades after use of virginiamycin began in food-producing animals. See B. Pavan, Synercid Aventis, 1 Current Opinion Investigational Drugs 173 (2000). Q/D remains a drug of last resort for certain highly-resistant infections, in part due to side effects. See Welte and Pletz (2010), pp. 391–393.
- 148.
Werner et al. (1998), p. 401.
- 149.
Werner et al. (2002), p. 81.
- 150.
The multitude of potential sources of antimicrobial use in both veterinary and human clinical environments for other drugs makes assessment of cause more difficult. See infra. In the case of virginiamycin, human uses of related streptogramins did not significantly contribute to antimicrobial pollution for that class of drugs, making this an unusual case and one scientifically useful to consider.
- 151.
Letter from Frank M. Aarestrup to Rep. Nancy Pelosi; Centner.
- 152.
Letter from Frank M. Aarestrup to Rep. Nancy Pelosi,; Preservation of Antibiotics for Medical Treatment Act of 2009: Hearing, (2009) (statement of Frank M. Aarestrup & Henrik Wegener), available at http://www.livablefutureblog.com/wp-content/uploads/2009/08/testimony-of-dr-frank-moller-aarestrup-1.pdf.
- 153.
This is determined according to milligrams of antibiotic used per kilogram of meat produced.
- 154.
Letter from Frank M. Aarestrup to Rep. Nancy Pelosi.
- 155.
Id.
- 156.
Id. at 1.
- 157.
In industrial animal production, animals often are sectioned into age groups, sometimes called production stages, because these animals will need to be fed differently according to weight and age. “Weaner” pigs are piglets that recently have been moved away from their mothers and a milk diet and onto other foods. Conventionally, this is done at 3–5 weeks of age. This process is stressful and weaner pigs, like many young food animals, are more susceptible than other age groups to diseases to which they might be exposed.
- 158.
Letter from Frank M. Aarestrup to Rep. Nancy Pelosi, at 1; Emborg and Wegener (2005); Aarestrup et al., Effect of Abolishment, (2001).
- 159.
Letter from Frank M. Aarestrup to Rep. Nancy Pelosi, at 1.
- 160.
Andreasen et al. at 42.
- 161.
Letter from Frank M. Aarestrup to Rep. Nancy Pelosi, at 1.
- 162.
Feed conversion is a measure of how much weight an animal gains as a function of the amount of feed it consumes. With efficient feed conversion, most of the feed consumed is used for weight gain. With poor feed conversion, feed (energy) may be used for other purposes (e.g., activity). An analogy is the difference between a human who has a sedentary lifestyle and gains weight rapidly and a human who is very active and, despite having a similar caloric intake, does not gain weight rapidly.
- 163.
Letter from Frank M. Aarestrup to Rep. Nancy Pelosi, at 1.
- 164.
Andreasen et al., at 41–42; Castanon (2007), pp. 2466, 2469–2470 (concerning the legal grounds for permitting antimicrobials in animal feeds in the European Union, particularly the harmonization of restrictions in certain member countries established before accession into European Union membership).
- 165.
These regulatory efforts have not gone unchallenged. Both Alpharma and Pfizer, major pharmaceutical companies that make and market drugs for non-therapeutic use in livestock in the United States and Europe, attempted to overturn the European bans on the basis of (1) alleged errors of risk assessment relating to the scientific evidence, and (2) alleged misapplication of powers, in this case: the application of the precautionary principle, which allows for regulation to proceed when evidence exists for harm but data are incomplete. European Courts dismissed the cases brought by Alpharma and Pfizer on the grounds that the European Commission, in mandating the original and amended legislation concerning restrictions on feed additives, had proper authorization to do so pursuant to its directive for the protection of animal or human health or the environment. See Case T-70/99, Alpharma, Inc. v. Council Euro. Union, 2002 E.C.R. II-03495; Case T-13/99, Pfizer Animal Health SA v. Council Euro. Union, 2002 E.C.R. II-3305; Council Directive 70/524, 1970 O.J. (L270) (EC).
- 166.
Council Directive 97/6, 1197 O.J. (L272) (EEC).
- 167.
The antimicrobials were: spiramycin, tylosin, bacitracin zinc, and virginiamycin. Soulsby (2007), p. i78.
- 168.
Council Regulation 2821/98, 1998 O.J. (L351) (EEC).
- 169.
Centner, at 2; Soulsby (2007), p. i77; Goforth & Goforth, at 49; see supra.
- 170.
Collignon et al. (2009), p. 132; World Health Org., WHO Global Strategy for Containment of Antimicrobial Resistance (2001), http://www.who.int/csr/resources/publications/drugresist/WHO_CDS_CSR_DRS_2001_2_EN/en/.
- 171.
The antimicrobials were: monensin, avilamycin, salinomycin, and flavomycin. Soulsby (2007), p. i78.
- 172.
Id.
- 173.
Werner et al., Molecular Analysis, (2002) at 90; van den Bogaard et al., at 146–48.
- 174.
Agerso and Aarestrup (2013), p. 569.
- 175.
Id, at 572.
- 176.
21 U.S.C. §§ 301–399.
- 177.
Id.
- 178.
- 179.
Tollefson et al. (1997), pp. 709–710 (citing concerns with food animal use of antimicrobials, particularly in animal feed).
- 180.
Baytril®, or enrofloxacin, is a relative of the human drug ciprofloxacin used to treat humans exposed to the bioterrorism agent anthrax. Ciprofloxacin also is used to treat humans with other clinically-important infections.
- 181.
Zhao et al. (2010), p. 7949; Animal Drugs, Feeds, and Related Products; Enrofloxacin for Poultry; Withdrawal of Approval of New Animal Drug Application, 70 Fed. Reg. at 44, 048.
- 182.
Nielsen and Gyrd-Hansen (1997), p. 246.
- 183.
Love et al. (2011a), pp. 279–283.
- 184.
- 185.
C. jejuni is a food-borne enteric pathogen that may be found in poultry at high rates (90–100 % of birds) without causing signs of disease in the birds. See McCrea et al. (2006a), p. 2908.
- 186.
- 187.
- 188.
Kassenborg et al. (2004), p. S279.
- 189.
Smith et al. (1999), p. 1525.
- 190.
Enrofloxacin for Poultry; Opportunity for a Hearing, 65 Fed. Reg. 64,954 (Oct. 31, 2000).
- 191.
Tollefson et al., Regulation of Antibiotic Use in Animals, (1997) at 418–23; see supra.
- 192.
21 U.S.C. § 360b(e)(1)(B) (2010); Tollefson et al., Regulation of Antibiotic Use in Animals, (1997) at 418–23.
- 193.
Briceno, at 5–6 (Of note, this occurs in the context of a regulatory hearing before a hearing officer under Part 16 of the regulations, and can be appealed to the Commissioner).
- 194.
21 U.S.C. § 360b(e)(1)(B); Tollefson et al., Regulation of Antibiotic Use in Animals, (1997) at 423.
- 195.
Toxic Substances Control Act, 15 U.S.C. § 2603 (2010).
- 196.
Ctr. Veterinary Med., U.S. Food & Drug Admin., Human Health Impact of Fluoroquinolone Resistant Campylobacter Attributed to the Consumption of Chicken 2 (2000), available at http://www.fda.gov/downloads/AnimalVeterinary/SafetyHealth/RecallsWithdrawals/UCM152308.pdf.
- 197.
Id. at 2.
- 198.
Id.
- 199.
Ramanan Laxminarayan & Anup Malani, Extending the Cure: Policy Responses to the Growing Threat of Antibiotic Resistance 106 (2007), available at http://www.rwjf.org/files/research/etcfullreport.pdf.
- 200.
Zhao et al. (2010) at 7949; Animal Drugs, Feeds, and Related Products; Enrofloxacin for Poultry; Withdrawal of Approval of New Animal Drug Application, 70 Fed. Reg. at 44,048.
- 201.
The uncertainties inherent to any risk assessment, which are particularly profound for microbial risk assessment, were attacked by Bayer, the company that produces Baytril®, during its effort to stop the FDA’s withdrawal of approval. See Briceno, at 5–6. These risk assessment techniques have also been hotly debated in the scientific community. See Feingold et al. (2010), p. 1170; Toze et al. (2010), p. 1038.
- 202.
Preservation of Antibiotics for Medical Treatment Act: Hearing before the H. Comm. on Rules, 111th Cong. 27 (2009) (statement of Margaret Mellon) (noting FDA’s failure to use its authority to restrict antibiotic use except in the case of fluoroquinolones in poultry).
- 203.
See infra Appendix I: Regulatory Timeline.
- 204.
President’s National Food Safety Initiative, 62 Fed. Reg. 13,589 (Mar. 21, 1997) (which improved coordination among agencies by clarifying their roles in prevention and emergence of resistant pathogens).
- 205.
Risk assessment is a process used by government agencies and other groups, including industry, to characterize and quantify hazards associated with certain activities. Originally designed for assessment of toxicants, risk assessment more recently has been applied to hazards of microbial origin, including concerns with antimicrobial resistance.
- 206.
U.S. Food & Drug Admin., A Proposed Framework for Evaluating and Assuring the Human Safety of the Microbial Effects of Antimicrobial New Animal Drugs Intended for Use in Food-producing Animals (1998), available at www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/VeterinaryMedicineAdvisoryCommittee/ucm126607.htm; U.S. Food & Drug Admin., Guidance for Industry #152, (2003).
- 207.
U.S. Food & Drug Admin., A Proposed Framework, (1998).
- 208.
Ctr. Veterinary Med., Draft Guidance #209.
- 209.
Ctrs. for Disease Control & Prevention, Interagency Task Force on Antimicrobial Resistance (2011), www.cdc.gov/drugresistance/actionplan/taskforce.html; James M. Hughes, Statement on Antimicrobial Resistance: Solutions to a Growing Public Health Threat (1999), available at www.hhs.gov/asl/testify/t990225c.html. The Task Force began work before formal Congressional action to organize and fund it was passed in 2000 through H.R. 2498. See Resources for the Future, Policy Responses to the Growing Threat of Antibiotic Resistance. Extending the Cure: Policy Brief 9 (May 2010), available at www.extendingthecure.org.
- 210.
Interagency Task Force on Antimicrobial Resistance, A Public Health Action Plan to Combat Antimicrobial Resistance (2001), available at http://www.cdc.gov/drugresistance/actionplan/aractionplan-archived.pdf.
- 211.
Id. at 2.
- 212.
Initial members included the Agency for Healthcare Research and Quality, the Health Care Financing Administration, the Health Resources and Services Administration, the Department of Agriculture, the Department of Defense, the Department of Veterans Affairs, and the Environmental Protection Agency. Later, the Centers for Medicare and Medicaid Services and the Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response were added.
- 213.
Interagency Task Force on Antimicrobial Resistance (2001).
- 214.
Interagency Task Force on Antimicrobial Resistance, A Public Health Action Plan to Combat Antimicrobial Resistance: 2011 Revision (2011), available at http://www.cdc.gov/drugresistance/pdf/public-health-action-plan-combat-antimicrobial-resistance.pdf.
- 215.
Interagency Task Force on Antimicrobial Resistance, National Action Plan for Combating Antimicrobial Resistant Bacteria (2015), available at https://www.whitehouse.gov/sites/default/files/docs/national_action_plan_for_combating_antibotic-resistant_bacteria.pdf.
- 216.
Issued by President Barack Obama on September 18, 2014; The renamed “National Action Plan” also supports the World Health Assembly resolution 67.25, endorsed in May 2014, concerning antimicrobial resistance.
- 217.
Id.
- 218.
See supra Part 10.3.1.2.
- 219.
Interagency Task Force on Antimicrobial Resistance (2011), at 17 (some reports are pending publication).
- 220.
Id. at 65.
- 221.
Animal Drugs, Feeds, and Related Products; Enrofloxacin for Poultry; Withdrawal of Approval of New Animal Drug Application, 70 Fed. Reg. 44,048 (Aug. 1, 2005) (to be codified at 21 C.F.R. pts. 520 & 556); see infra.
- 222.
Interagency Task Force on Antimicrobial Resistance (2011), at 6. According to a presentation by the Task Force at a public meeting for comment (November 15, 2011 in Washington, D.C.), at the time of writing, the Task Force plans to expand NHSN further, including collection of data on geographic distribution of infections in healthcare settings.
- 223.
Interagency Task Force on Antimicrobial Resistance (2008), at 18.
- 224.
Id. at 19.
- 225.
Jones (1996), p. 153.
- 226.
Mellon et al. (2009), p. 65.
- 227.
Id. at 65–66.
- 228.
21 U.S.C. § 360b(l) (2010).
- 229.
Dave Love, Drug Amounts for Food Animals Now Reported by FDA: Thanks, It’s About Time!, Johns Hopkins Center for a Livable Future Blog (Dec. 13, 2010), www.livablefutureblog.com/2010/12/drug-amounts-for-food-animals-now-reported-by-fda-thanks-it%E2%80%99s-about-time (regarding the need to report amounts by specific drug and also by use in food-producing animals).
- 230.
Letter from Am. Ass’n Avian Pathologists et al., to Michael B. Enzi, Ranking Member, Senate Comm. on Health, Education, Labor & Pensions (Nov. 18, 2009), available at http://www.meatami.com/ht/a/GetDocumentAction/i/55364 (urging defeat of the bill); Kennedy, (2010); Food Marketing Inst., Low-Level Use of Antibiotics in Livestock and Poultry, available at http://www.fmi.org/docs/media/bg/antibiotics.pdf (last visited Sept. 16, 2011); Timothy S. Cummings, Stakeholder Position Paper: Poultry, 73 Preventive Veterinary Medicine 209 (2006).
- 231.
Interagency Task Force on Antimicrobial Resistance (2001), at 29.
- 232.
See supra ITFAR 2015, at 9.
- 233.
See supra ITFAR 2015, at 5.
- 234.
U.S. Food & Drug Admin., A Proposed Framework, (1998).
- 235.
U.S. Food & Drug Admin., Guidance for Industry #152, (2003).
- 236.
Id.
- 237.
U.S. Food & Drug Admin., Guidance for Industry #152, (2003); Tollefson (2004), p. 415.
- 238.
FDA’s Role in Antimicrobial Resistance: Hearing, (2008) (statement of Bernadette Dunham).
- 239.
Preservation of Antibiotics for Medical Treatment Act of 2009: Hearing, (2009) (statement of Joshua Sharfstein).
- 240.
Alternative methods are not detailed expressly in the document; instead, industry is urged to discuss possible alternatives with FDA officials. U.S. Food & Drug Admin., Guidance for Industry #152, (2003), at 1–2.
- 241.
Comments were solicited through the end of August 2010, and the FDA has stated that it intends to issue a final document. At the time of writing, the timeline for the final document is unknown. See Ctr. Veterinary Med., Draft Guidance #209.
- 242.
U.S. Food & Drug Admin., The Judicious Use of Medically-Important Antimicrobial Drugs in Food-Producing Animals (2012), available at http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM216936.pdf.
- 243.
Id. at 17.
- 244.
Id. at 3.
- 245.
Id.
- 246.
Id.
- 247.
Id. at 13–15.
- 248.
U.S. Food & Drug Admin., Proposal to Withdraw Approval of the New Animal Drug Application for Enrofloxacin for Poultry 5 (Docket no. 00 N-1571, Mar 16, 2004); Ctr. Veterinary Med., Draft Guidance #209, at 11 (“However, initiating action to withdraw an approved new animal drug application (NADA), in whole or in part, based on the results of a post-approval safety review would require the agency to make the showing required under section 512(e)(1) of the [Food Drug and Cosmetic] Act.”).
- 249.
Love et al. (2011a), p. 280.
- 250.
Boucher et al. (2009), p. 1.
- 251.
U.S. Dep’t Agric., Veterinary Medicine Loan Repayment Program (2011), www.csrees.usda.gov/nea/animals/in_focus/an_health_if_vmlrp.html.
- 252.
Am. Veterinary Med. Ass’n, AVMA Responds to Federal Register Request for Comments (2010), available at http://www.avma.org/advocacy/federal/regulatory/public_health/judicious_use_antimicrobial_drugs.asp.
- 253.
Id.
- 254.
i.e. by the end of 2016, or longer, if the FDA deems this necessary.
- 255.
Supra FDA, Guidance#213 at 8.
- 256.
Id.
- 257.
Supra FDA, Guidance#213 at 5.
- 258.
Use of growth promoting antibiotics in medicated animal feed was shown to be associated with increased rates of animal weight gain. Love et al. (2011a), p. 280. However, the use of antibiotics in feed was coupled with industrialization of the animal production process, in which high-throughput techniques were combined with single-species raising in small spaces (barns or feedlots) and commodity feed supplementation, see Pew Comm’n Indus., (2008). As a result, disentangling the exact mechanism of action of the antibiotics used for growth promotion has been difficult; scientists and others speculate that bacterial metabolic effects, host microbial ecology effects, and effects from treatment of sub-clinical disease may play roles independently or in combination. See Kiser, at 1063. Further, in some settings, use of growth promoting antibiotics has been shown to have little or no positive effect on animal growth and no economic benefit. See Graham et al. (2007), p. 79.
- 259.
Love et al. (2011a), p. 280.
- 260.
21 C.F.R. § 558 (2010).
- 261.
Id.
- 262.
Id.
- 263.
Type A medicated articles are used for manufacture of another Type A medicated article or for production of Type B or Type C medicated feed. Type B medicated feeds are used for the manufacture of other medicated feeds and contain nutrients (e.g., minerals or vitamins). Type C medicated feeds are complete feeds (i.e., contain all nutrients needed) or are “top-dressed” feeds (often literally placed on top of other feed). These are offered as free-choice supplements, meaning that animals choose how much of the medicated feed--and therefore the drug--to consume. These contain nutrients (e.g., vitamins, minerals) and other nutritional ingredients, and are produced by diluting Type A medicated articles or Type B medicated feeds. Certain licenses are required for manufacturers, or feed mills, of Type B or Type C medicated feeds. See id.
- 264.
Mitchell et al. (1998), pp. 742–743.
- 265.
Tollefson et al. (2006), p. 421.
- 266.
van Houweling and Gainer (1978), p. 1413.
- 267.
21 C.F.R. § 558.
- 268.
21 C.F.R. § 512(b).
- 269.
Unlike actual prescriptions, VFD orders circumvent state pharmacy laws while providing for a higher degree of professional control than the typical, over-the-counter labels approved for the majority of medicated animal feeds. See 21 U.S.C. § 354. At the time of writing, this category only had been used for one new antimicrobial, Schering-Plough’s Aquaflor®, or florfenicol (a drug related to chloramphenicol), approved in 2005 (NADA 141–246; a Type A medicated feed article used to make Type C medicated feed for catfish). See Appendix II: Critically-Important Antimicrobials. Chloramphenicol is rarely employed for human clinical use due to toxicity concerns. See Editorial, Fatal Aplastic Anemias from Chloramphenicol, 247 New Eng. J. Med. 183 (1952).
- 270.
Veterinary Feed Directive: Final Rule, 65 Fed. Reg. 76,924 (Dec. 8, 2000) (to be codified at 21 C.F.R. pts. 510, 514, 558).
- 271.
Am. Veterinary Med. Ass’n, AVMA Submitted Comments Regarding the Veterinary Feed Directive (Aug. 26, 2010), available at http://www.avma.org/advocacy/federal/regulatory/practice_issues/drugs/Veterinary_Feed_Directive.asp; Greg Cima, Antimicrobial Oversight Could Increase Through VFDs, JAVMA News (November 15, 2011), available at http://www.avma.org/onlnews/javma/nov11/111115p_pf.asp (regarding the American Association for Bovine Practitioners’s support of VFD oversight of over-the-counter antimicrobial drugs for food animal use).
- 272.
H.R. 1150, re-introduced by Rep. Louise Slaughter (D-NY, a microbiologist) on March 14, 2013. This act originally was introduced by Representative Brown (D-OH) to the 106th Congress in 1999, and most recently had been introduced to the House of Representatives by Rep. Slaughter and to the Senate by Sen. Diane Feinstein (C-DA) in 2011. PAMTA would amend Sections 201 and 512 of the Federal Food, Drug and Cosmetic Act to rescind approval for certain critically-important antimicrobials for production uses in food-producing animals.
- 273.
Teillant and Laxminarayan (2015).
- 274.
U.S. Gen. Accounting Office, (2004).
- 275.
See supra.
- 276.
See supra.
- 277.
Boucher et al. (2009), p. 1.
- 278.
Aarestrup et al., Resistance in Bacteria, (2008) (reviewing options for strategies to control antimicrobial resistance and their anticipated effectiveness from a scientific perspective).
- 279.
Collignon et al. (2009).
- 280.
Silbergeld et al. (2008a), p. 156.
- 281.
- 282.
In an October 12, 2010 letter to Rep. Louise Slaughter, the Food and Drug Administration noted that NARMS personnel are exploring the possibility of adding S. aureus to the list of tested organisms. Letter from Jeanne Ireland, Assistant Comm’r Legislation, U.S. Food & Drug Admin., to Rep, Louise Slaughter, U.S. House of Representatives (Oct. 12, 2010), available at http://www.keepantibioticsworking.com/new/KAWfiles/64_2_107766.pdf.
- 283.
Ricardo Castillo et al., Antimicrobial Resistant Bacteria: An Unrecognized Work-Related Risk in Food Animal Production, Safety & Health at Work (invited paper, in submission, 2011; on file with author).
- 284.
Scott Weese (2006).
- 285.
Loeffler et al. (2010), p. 282.
- 286.
Smith et al. (2009), p. e4258.
- 287.
- 288.
This strain designation, ST398, is based on genetic methods using a process known as multi-locus sequence typing. Other typing mechanisms, such as pulsed-field gel electrophoresis (PFGE) may generate a different “name.” ST398 originally was known as a PFGE non-typable (NT-)MRSA.
- 289.
Harper et al. (2010), p. 101.
- 290.
Kadlec and Schwarz (2010), p. 3589.
- 291.
Halpern, at 4–5.
- 292.
Weese (2006), p. 445.
- 293.
Id.
- 294.
- 295.
Chomel and Sun (2011), p. 167.
- 296.
Bramble et al. (2011), p. 617.
- 297.
The agenda of the Antimicrobial Resistance Summit (2011) was integrating surveillance and regulation with infection prevention activities in multiple settings, and with education and research efforts. See Gottlieb and Nimmo (2011), p. 281.
- 298.
See supra.
- 299.
Silbergeld et al. (2008b), pp. 1392–1393 (concerning movement of pathogens and resistant bacteria between the hospital and the community).
- 300.
Johannsson et al. (2011), pp. 367–372 (regarding the need to include small community hospitals in computerized networks and provide other incentives for participation in antimicrobial stewardship programs).
- 301.
Gottlieb and Nimmo (2011), p. 282.
- 302.
This may occur because the genes for resistance may co-locate to the same mobile genetic element. See Silbergeld et al. (2008b), p. 1394.
- 303.
H.R. 965.
- 304.
S. 1211.
- 305.
Supra note 94.
- 306.
Davis et al. (2009), p. 528 (concerning prohibited extra-label uses; others may be allowed).
- 307.
McReynolds et al. (2000), pp. 1524–1525.
- 308.
Certain drug efflux pumps will provide resistance to multiple families of antibiotics. In addition, other characteristics, such as the thickness of a cell wall, may help exclude antibiotics from a bacterium, conferring partial resistance. The latter is one mechanism of action for partial vancomycin resistance in some MRSA isolates. See Howden et al. (2010), pp. 99, 107–109.
- 309.
Cavaco et al. (2011), p. 344.
- 310.
Shen et al. (2011) pp. 7128–7133.
- 311.
Nannapaneni et al. (2009), p. 1348; see supra.
- 312.
Campylobacter jejuni may colonize chickens at high rates without causing disease, making contamination of food products more likely. See McCrea et al. (2006b), pp. 136–143. Campylobacter is the leading cause of foodborne illness in the United States, responsible for an estimated 2 million human infections annually. See Samuel et al. (2004), p. S165.
- 313.
U.S. Food & Drug Admin., National Antimicrobial Resistance Monitoring System: 2009 Executive Report 82 (2011), available at http://www.fda.gov/AnimalVeterinary/SafetyHealth/AntimicrobialResistance/NationalAntimicrobialResistanceMonitoringSystem/ucm268951.htm; Zhao et al., (2010) at 7951 (noting trend in ciprofloxacin resistance in figure 1).
- 314.
This simple analysis was performed by the author (MFD). Methods: Briefly, data on the proportion of resistant isolates, by type and year, were adapted from the NARMS 2009 (360) report to Stata 11 (College Station, TX). A linear regression model was run on the proportion of ciprofloxacin resistance compared to a dichotomous variable (after vs. before the ban) for time trend, and clustering within type of isolate (human, chicken breast, and chickens). Results: After the ban, on average, the proportion of ciprofloxacin resistance increased 0.029 (~3 %), and this estimate was statistically significant (p = 0.008). No statistical differences were seen by type of isolate, controlling for year (p = 0.36). Overall averages for percentage of ciprofloxacin resistance found since the ban (for humans, chicken breasts, and chickens combined) were: 21.3 % (2009), 23.0 % (2008), 21.5 % (2007), and 14.9 % (2006). See U.S. Food & Drug Admin., National Antimicrobial Resistance Monitoring System: 2009 Executive Report, 362, at 82.
- 315.
- 316.
U.S. Food & Drug Admin., NARMS 2009 Retail Meat Report 9 (2009), available at http://www.fda.gov/AnimalVeterinary/SafetyHealth/AntimicrobialResistance/NationalAntimicrobialResistanceMonitoringSystem/ucm257561.htm.
- 317.
Lohren et al. (2008), pp. 132–133.
- 318.
U.S. Food & Drug Admin., FDA Approves Fluoroquinolone Product for Use in Cattle (1998), available at http://www.fda.gov/AnimalVeterinary/NewsEvents/FDAVeterinarianNewsletter/ucm089486.htm.
- 319.
Le Hello et al. (2011), p. 679.
- 320.
Laxminarayan and Malani (2007), p. 50.
- 321.
Silbergeld et al. (2008a), pp. 156–157.
- 322.
See supra.
- 323.
Cohen et al. (1989), p. 1318.
- 324.
U.S. Food & Drug Admin., National Antimicrobial Resistance Monitoring System: 2009 Executive Report, 362, at 82 (Data on cross-resistance, however, are not available in published reports, which provide only prevalences of resistance in particular pathogens by source, i.e., food animals, retail meat, or humans).
- 325.
Shen et al. (2011).
- 326.
Ctr. Veterinary Med., Human Health Impact, (2000) at 2.
- 327.
Kiser, at 1062.
- 328.
Letter from Rep. Tom Latham, U.S. House of Representatives, to Lester M. Crawford, Acting Comm’r, U.S. Food & Drug Admin. (Sept. 1, 2004), available at http://www.fda.gov/ohrms/dockets/dockets/00n1571/00n-1571-m000006-vol403.pdf (in which Representative Latham suggests that FDA should have “scientific certainty” to ban fluoroquinolone use).
- 329.
This is similar to the burden of ascribing a “cause” for cancer in a particular individual suffering from its effects, particularly when the cancer is potentially linked to many sources (e.g., diet, smoking habits, chemical exposures, and genetics). However, chemicals and commercial products (e.g., cigarettes) have been regulated despite this difficulty. Further, for chemicals, in vitro (cell culture) and in vivo (laboratory animal) assays demonstrating carcinogenicity in the laboratory prove sufficient for risk assessment purposes. On the contrary, similar laboratory and field assays demonstrating the ability of antibiotics to select for resistance and promote transfers of genetic material in bacteria conferring resistance are attacked by opponents of regulation as insufficient evidence of harm. Cummings, (2006) at 209–12.
- 330.
Muto et al. (2003), p. 362.
- 331.
After all, Fleming discovered penicillin by isolating it from the mold Penicillium.
- 332.
Wright (2007), pp. 183–184.
- 333.
- 334.
Mullner et al. (2009), p. 1311. In this study, surveillance and laboratory data were combined, and isolates tested using molecular techniques, to determine that most cases of human campylobacteriosis were attributable to poultry. Government intervention in poultry production practices led to a decline in human cases. New Zealand’s relative isolation--as an island country--likely enhanced the determination of cause. See id.
- 335.
Smith et al. (1999), pp. 1525–1532.
- 336.
Supra note 94, New Animal Drugs; Cephalosporin Drugs; Extralabel Animal Drug Use; Order of Prohibition at 743 (61 FR 57732 and 57738, November 7, 1996). (At the time of writing, this order of prohibition was still in public comment and was scheduled to take effect in April, 2012).
- 337.
Goforth & Goforth, at 12.
- 338.
Cohen et al. (1989), pp. 1318–1325.
- 339.
Davis et al. (2011), pp. 247–248.
- 340.
Li et al. (2010), p. 3444.
- 341.
- 342.
Graham et al. (2011), p. 418.
- 343.
Ji et al. (2010), p. 641.
- 344.
Graham and Nachman (2010), p. 653; Love et al. (2012).
- 345.
Ji et al. (2010).
- 346.
Interagency Task Force on Antimicrobial Resistance (2001), at 30 (discussing role of EPA in antibiotic and antibiotic pesticide registrations).
- 347.
Wright (2007).
- 348.
Love et al. (2011a), p. 280 (particularly figure 1).
- 349.
Nat’l Res. Council, Toward a Unified Approach to Dose-Response Assessment, in Science and Decisions: Advancing Risk Assessment 128 (2009).
- 350.
Amy R. Sapkota et al. Lower Prevalence of Antibiotic-Resistant Enterococci on U.S. Conventional Poultry Farms That Transitioned to Organic Practices, Envtl. Health Persps. (accessed ahead-of-print, 2011).
- 351.
Goforth & Goforth, at 70.
- 352.
Animal & Plant Health Inspection Serv., U.S. Dep’t Agric., Dairy 2007 Part III: Reference of Dairy Cattle Health and Management Practices in the United States (2008), available at http://www.aphis.usda.gov/animal_health/nahms/dairy/downloads/dairy07/Dairy07_dr_PartIII_rev.pdf.
- 353.
See supra.
- 354.
Am. Veterinary Med. Ass’n., AVMA Responds, (2010).
- 355.
At the time of writing, only one specific federal incentive existed to support entry of veterinarians into food animal practice, public practice, and research. The Veterinary Medicine Loan Repayment Act (VMLRP) is a small program to help provide partial repayment of educational loans, but only in specific, designated shortage areas that require nomination by state health officials. See U.S. Dep’t Agric., Veterinary Medicine Loan Repayment Program, (2011) . The average veterinary student loan burden is $130,000, and the average starting salary is $65,000 and may be lower in rural areas. See Scott R. Nolen, JAVMA News: Student Loan Subsidy’s End Raises Concerns, Sept. 15, 2011), available at http://www.avma.org/onlnews/javma/sep11/110915u.asp.
- 356.
U.S. Dep’t Agric., Animal Health: National Veterinary Accreditation Program (2011), http://www.aphis.usda.gov/animal_health/vet_accreditation/.
- 357.
Supra Guidance #213, at 7.
- 358.
Meghan Davis & Tyler Smith. More Data, Better Data: How FDA Could Improve the Animal Drug User Fee Act, Center for a Livable Future Blog (Nov. 15, 2011), available at: http://www.livablefutureblog.com/2011/11/adufa-more-data-better-data (providing details of comments by the author (MFD) given during a public meeting at FDA in Rockville, Maryland on Nov. 7, 2011 regarding reauthorization of ADUFA).
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Cummings (2006), pp. 209–212.
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U.S. Dep’t Agric., Census of Agriculture, (2007).
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See supra.
- 362.
Penicillin-Containing Premixes: Opportunity for Hearing, 42 Fed. Reg. 43772 (Aug. 30, 1977) (“Penicillin NOOH”); Tetracycline NOOH, 42 Fed. Reg. 56264 (Oct. 21, 1977).
- 363.
Penicillin Containing Premixes; Opportunity for Hearing, 42 Fed. Reg. 43,772, 43,772 (Aug. 30, 1977).
- 364.
Docket No. FDA-1999-P-1286 and Docket No. FDA-2005-P-0007.
- 365.
NRDC et al. v. FDA et al. 11 Civ 3562 (RMB).
- 366.
NRDC et al. v. FDA et al. 11 Civ 3562 (THK), http://www.hpm.com/pdf/blog/NRDC%20-%20SDNY%20CP%20Decision.pdf.
- 367.
United States Court of Appeals for the Second Circuit, August Term, 2012. Docket Nos. 12-2106-cv(L), 12-3607-cv(CON), decided July 24, 2014. http://docs.nrdc.org/health/files/hea_14072401a.pdf.
- 368.
- 369.
- 370.
World Veterinary Year 2011 (2011), www.vet2011.org/.
- 371.
Ctr. Veterinary Med., Draft Guidance #209, 37, at 4; Am. Veterinary Med. Ass’n, AVMA Responds, (2010).
- 372.
Possible exceptions could include antibiotics that have been tested for resistance and cross-resistance by multiple, independent researchers and proven not to be a threat to public health.
- 373.
O’Brien (1997), p. S2.
- 374.
A key conclusion of the Australian Society for Infectious Diseases/Australian Society for Antimicrobials’ Antimicrobial Resistance Summit (Feb. 7-8, 2011) was the need for “a national interdisciplinary body . . . to manage the looming antimicrobial resistance crisis.” See Gottlieb & Nimmo, (2011) at 281.
- 375.
Coast and Smith (2003), p. 242.
- 376.
U.S. Food & Drug Admin., Guidance for Industry #152, (2003); Ctr. Veterinary Med., Draft Guidance #209, 37; H.R. 965; S. 1211.
- 377.
Wright (2007), pp. 175–186.
- 378.
Press Release, Office Press Sec’y, White House, U.S.-EU Joint Declaration and Annexes (Nov. 3, 2009), available at http://www.whitehouse.gov/the-press-office/us-eu-joint-declaration-and-annexes.
- 379.
Monecke et al. (2011), p. e17936 (demonstrating international movement of clones of MRSA).
- 380.
Incremental regulations should not be held to the same standards of evaluation as more comprehensive, multi-agency regulatory efforts, since partial or limited restrictions may be equally limited in their ability to achieve the desired public health effect.
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Davis, M., Rutkow, L. (2017). Meat Production and Antibiotics Use. In: Steier, G., Patel, K. (eds) International Farm Animal, Wildlife and Food Safety Law. Springer, Cham. https://doi.org/10.1007/978-3-319-18002-1_10
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