Animal Health and Antibiotics Looking Ahead with Science

Transcription

1 Animal Health and Antibiotics Looking Ahead with Science t

2 The Overton Window Unthinkable Radical Acceptable Sensible Popular Policy Prohibition of therapeutic uses of medically important antimicrobials Prohibition of prevention and control uses of medically important antimicrobials Prohibition of growth promotion uses of medically important antimicrobials

3 AMDUCA? The same regulations as published in the Federal Register in 1996 still apply today. The AMDUCA regs were utilized to limit the ability to use cephalosporins in an extralabel manner in food animals.

4 Guidance Documents Guidance for Industry (GFI) 209 April, 2012 Imagining a delineation between growth promotion, prevention/control, and therapy judicious vs. hazard Principle 1: The use of medically important antimicrobial drugs in food-producing animals should be limited to those uses that are considered necessary for assuring animal health.

5 U. S. CTC, TC and OTC Cattle Approval Examples (Feed and Water) Feed efficiency/rate of gain Prevention/Control Treatment CTC: 10 mg/lb BW for up to 5 days CTC: 400 g/ton to provide 10 mg/lb per day in calves up to 250 lbs TC: 22 mg/kg for 3-5 days in calves OTC: 0.5 to 2.0 g/hd per day????? CTC: 350 mg/hd per day in beef cattle under 700 lbs CTC: 0.5 mg/lb per day in beef cattle over 700 lbs CTC: 350 mg/hd per day in beef cattle CTC: mg/hd per day in calves lbs Gone as of January 1, 2017 CTC: 70 mg/hd per day in growing cattle over 400 lbs CTC: 0.1 mg/hd per day in calves up to 250 lbs These are not all of the CTC, TC, and OTC indications, but are selected to illustrate the regimen range.

6 However, the Agency believes that it is not limited to making risk determinations based solely on documented scientific information, but may use other suitable information as appropriate.

7 Who defines medically important? Appendix A, GFI #152 List is determined by an expert FDA panel managed by the Center for Drug Evaluation and Research (CDER) Within the FDA The World Health Association also has a list of medically important antibiotoics Human health Animal health

8 WHO Prioritization within the critically important designation Glycopeptides Fluoroquinolones Cephalosporins Macrolides

9 Antimicrobials Not Classified as Medically Important Ionophores: monensin, lasalocid Flavophospholipol: bambermycins (e.g., Flavomycin, Gainpro ) Bacitracin Pleuromutilins: Tiamulin Not medically important in the U.S., but classified as highly important by WHO

10 Medically Important Antimicrobials with Feed or Water Labels Aminoglycosides: gentamicin, neomycin Lincosamides: lincomycin Macrolides: tylosin, tilmicosin (Pulmotil currently requires a VFD in swine and cattle) Penicillins (natural): penicillin G included in combination products Florfenicol: CHPC included as highly important drug in GFI #152 appendix A, Florfenicol is considered medically important. Existing VFD status for feed in aquaculture.

11 Medically Important Antimicrobials with Feed or Water Labels Streptogramins:virginiamycin Sulfonamides: Includes both potentiated (e.g., trimethoprim/sulfa) and non-potentiated sulfonamides. Tetracyclines: chlortetracycline, oxytetracycline, tetracycline

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13 Guidance for Industry 213 December, 2013 This guidance document puts forth nonbinding recommendations for companies to comply with Guidance 209. There was a 3 month period for companies to communicate with the FDA/CVM regarding their intent to comply with the voluntary recommendations in Guidance 209. A 3 year period for companies to comply ends in December of 2016.

14 GFI 213 A company may remove the label indications for growth promotion and insert label requirements for veterinary authorization without being subjected to other requirements such as updating the label in other areas (e.g., microbial safety).

15 The VFD in one slide Written only, non-verbal Feed, free choice feed, hand fed feed, milk, milk replacer are feeds Absolutely no extralabel use Starting January 1, 2017, must have a VFD to feed the feed containing a VFD drug to food animals An animal only appears on a VFD once, multiple VFDs required for pulsing Type A medicated articles are not feeds, Type B and Type C medicated feeds are feeds.g

16 Some Other Hot Topics

17 California SB27 Goes beyond GFI #209 Routine prevention All antibiotics under veterinary control

18 Penicillin/Tetracyclines in Animal Feed 1977 NOOH on the use of penicillins and tetracyclines in animal feed 2011 NRDC, CSPI, UCS, FACT filed a law suit in U.S. District Court to force the CVM to have the hearings 2012 Judge says CVM must have the hearings 2012 Appeal by HHS/FDA/CVM 2014 Ruling in favor of FDA Appeal?

19 Executive Order The Executive Order directs establishment of the Task Force for Combating Antibiotic-Resistant Bacteria, co-chaired by the Secretaries of Defense, Agriculture, and Health and Human Services (HHS).

20 Executive Order The Executive Order directs the Secretary of HHS, in consultation with the Secretary of Agriculture, to establish a Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria, to be composed of leading non-governmental experts

21 Executive Order The Presidential Advisory Council will provide advice, information, and recommendations regarding programs and policies intended to: preserve antibiotic effectiveness; strengthen surveillance of antibiotic-resistant infections; advance the development of rapid, point-of-care diagnostics for use in human healthcare and agriculture; advance research on new treatments for bacterial infections; develop alternatives to the use of antibiotics for some agricultural purposes; and improve international coordination of efforts to combat antibiotic resistance.

22 Executive Order The National Strategy provides detailed actions for five interrelated national goals to be achieved by 2020 in collaboration with partners in healthcare, public health, veterinary medicine, agriculture, and food safety, as well as in academic, Federal, and industrial research and development. The goals are: 1. Slow the emergence and prevent the spread of resistant bacteria. 2. Strengthen National efforts to identify and report cases of antibiotic resistance.

23 Executive Order The National Strategy 3. Advance the development and use of rapid diagnostic tests for the identification and characterization of antibiotic-resistant bacteria. 4. Accelerate basic and applied research and development for new antibiotics as well as other therapeutics and vaccines. 5. Improve international collaboration, capacities for antibiotic-resistance prevention, surveillance, control, and antibiotic research and development.

24 The veterinary profession is not only going to be responsible for all medically-important antimicrobial uses in food animals we are going to be accountable

25 Antibiotic Use Monitoring

26 Antimicrobial Use Monitoring In my opinion, should be actual use, tied to reason for use Total kg as a metric only serves as a stick to drive cut the use as a goal Animal Daily Doses (ADD) and Animal Regimens (AR) provide a look into drug exposure as well as number of animals receiving the regimen. There may be different regimens for the same drug in a species.

27 Antimicrobial Use Monitoring The only way to drive the needed granularity in the data is to Give agriculture the steering wheel for data collection Government audit of the sampling strategy and data handling Absolute guarantee of anonymity for participants Sampling structure must balance Ability to engage the same participants year after year New participants and random sampling of repeat participants each year for appropriate sampling of the industry. Granularity of public data and data used to drive antibiotic stewardship may vary

28 Fundamentals Denominators really, really matter Numerators are relatively easy And this has driven an interactive environment for this issue in which some engage based only on numerators

29 My View Stewardship is good, but no antibiotics not an option Never-ever systems where treated animals or groups are removed from the system are disingenuous It is about the system and the overall effect of the system on antibiotic use When there is an incentive to not treat an animal with an infectious disease, what do you think happens to speed of treatment and time to alleviation of an infectious disease?

30 What is Stewardship? 1. Responsibility for appropriate diagnostics and establishment of an accurate and functional case definition 5. Is this antibiotic intervention still necessary? Yes 2. Is there a non-antibiotic alternative which will appropriately prevent, control, or treat this disease challenge? 4. Assuring use of the antibiotic as shown to be safe and effective While 3. Selection of an antibiotic which has been demonstrated to be safe and effective for this purpose

31 Who is driving change in food animal antimicrobial use?

32 Drivers of Change in Food Animal Antimicrobial Use PARA S621 Legislation DART HR2459 PAMTA HR1552 ADUFA Cephalosporins VFD Regulation GFI 209 GFI 213 Fluoroquinolone s AMDUCA Tyson McDonald s Chipotle Retailation Panera Walmart Chic Fil - A

33 A Big Difference In duration of disease risk Chicken 4 # days 10# days Swine 6 months Beef cattle months

34 What price to say antibiotic free with no asterisk? Ionophores

35 Antimicrobial stewardship is cannot going to be used as a competitive advantage between or within food animal industries.

36 from here The days of verbal treatment protocols are gone The days of unacceptable treatment records are gone The days of nontransparent use of antimicrobials in food animals are coming to an end Neither veterinarians or producers can be passive in these efforts.

37 Antibiotic Resistance Issues

38 Alexander Fleming But I would like to sound one note of warning. Penicillin is to all intents and purposes nonpoisonous so there is no need to worry about giving an overdose and poisoning the patient. There may be a danger, though, in underdosage. It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them, and the same thing has occasionally happened in the body.

39 Rice LB. Mechanisms of resistance and clinical relevance of resistance to beta-lactams, glycopeptides, and fluoroquinolones. Mayo Clinic Proceedings, 97: , 2012.

40 Food Animal Antibiotic Use in the United States

41 Yearly sales data are available But the last publically available human data are from 2011.

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50 So, where does the "80% used in food animals" come from? Well, if you add the 4,122,397 kg of ionophores sales reported for 2011, then you come up with the following values. It doesn't move the value that much to take the ionophores out because they go into both the numerator and denominator. All Antimicrobial Sales Totals 13,569,039 3,289,175 Expressed as percent of total human and food animal sales 80.5% 19.5%

51 Food Animal Sales 2011 (kg) Human Sales 2011 (kg) Medically Important Antimicrobial Totals (kg) 9,446,641 3,289,175 Expressed as percent of total human and food animal sales of medically important antimicrobials 74.2% 25.8%

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53 Antibiotic-Resistant Microorganism Carbapenem Resistant Enterobacteriaceae (CRE) Drug-resistant Neisseria gonorrhoeae (any drug) Infections Included HAIs caused by Klebsiella and E. coli with onset in hospitalized patients Infections not Included Estimated Annual Number of Cases Estimated Annual Number of Deaths 1, 2, 3 9, All infections 246,000 <5 Multidrug-resistant Acinetobacter (three or more drug classes) HAIs with onset in hospitalized patients 1,2 7, Drug-resistant Campylobacter (azithromycin or ciprofloxacin) Drug-resistant Candida (fluconazole) Extended-spectrum β-lactamase producing Enterobacteriaceae (ESBLs) Vancomycin-resistant Enterococcus (VRE) Multidrug-resistant Pseudomonas aeruginosa (three or more drug classes) Drug-resistant non-typhoidal Salmonella (ceftriaxone, ciprofloxacin 7, or 5 or more drug classes) All infections 310, HAIs with onset in hospitalized patients HAIs caused by Klebsiella and E. coli with onset in hospitalized patients HAIs with onset in hospitalized patients HAIs with onset in hospitalized patients 1,2 3, ,2,3 26, ,2 20, ,2 6, All infections 100,000 40

54 Antibiotic-Resistant Microorganism Infections Included Infections not Included Estimated Annual Number of Cases Estimated Annual Number of Deaths Drug-resistant Salmonella Typhi (Ciprofloxacin 7 ) All infections 3,800 <5 Drug-resistant Shigella (Azithromycin or ciprofloxacin) All infections 27,000 <5 Methicillin-resistant Staphylococcus aureus (MRSA) Invasive infections 4 80, Streptococcus pneumoniae (full resistance to clinically relevant All infections 1,200, drugs) Drug-resistant tuberculosis (any clinically relevant drug) All infections 1, Vancomycin-resistant Staphylococcus aureus (VRSA) All infections <5 <5 Erythromycin-resistant Group A Streptococcus Invasive infections 5 1, Erythromycin-resistant Group B Streptococcus Invasive infections 6 7, Summary Totals for Antibiotic-Resistant Infections 2,049,442 1,473,442 23,488 22,130 Healthcare-associated Clostridium difficile Infections infections in acute care hospitals or in patients requiring hospitalization 250,000 14,000

55 1. Infections occuring outside of acute-care hospitals (e.g., nursing homes) 2. Infections acquired in acute care hospitals but not diagnosed until after discharge 3. Infections caused by Enterobacteriaceae other than Klebsiella and E. coli (e.g., Enterobacter spp.) 4. Both healthcare and community-associated non-invasive infections such as wound and skin and soft tissue infections 5. Non-invasive infections including common upper-respiratory infections like strep throat 6. Non-invasive infections and asymptomatic intrapartum colonization requiring prophylaxis 7 Resistance or partial resistance