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Great Plains Veterinary Educational Center Parts of the Puzzle.

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Presentation on theme: "Great Plains Veterinary Educational Center Parts of the Puzzle."— Presentation transcript:

1 Great Plains Veterinary Educational Center Parts of the Puzzle

2 Great Plains Veterinary Educational Center IBR at work

3 Great Plains Veterinary Educational Center the role of antibiotics in treating diseases caused by different bugs … focus on respiratory disease Shipping fever / BRD … set up by lack of immune protection stress, commingling, & timing Virus destroys cells that protect the lung … Bacteria move from their hang out to lung Lungs cells provide lots of food with very little defense

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6 Disease sequence of events: Susceptible animal exposed. Incubation is the period (time) from the first replication of the disease causing biological agent until sufficient compromise of the target organ(s) occurs causing loss of function of the target organ(s). Primary viral BRD this averages 3 days. Secondary bacterial BRD averages 3 to 5 days behind the initial viral infection.

7 Great Plains Veterinary Educational Center Disease sequence of events: Inflammation occurs in stages. Early, the body diverts white blood cells and blood in to the affected area typically causing swelling of tissue, both cells and spaces between cells. As the inflammation continues, loss of function of the affected tissue occurs. Late stage of inflammation is involved in the body trying to clean up, remove, or repair / reconstruct the damaged tissue. The late stage of inflammation is the first stage of recovery. … begins 7 to 10 days … last for weeks

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10 how the antibiotics work Antibiotic – mold, 1928 Protect molds from bacteria No effect on viruses or normal body cells Two types -static (slows) & cidal (kills) Four mechanisms –Cripples cell wall –Interferes with protein synthesis –Confuses metabolic processes –Blocks DNA / RNA synthesis Different bacteria … require different mechanisms to stop them …

11 Great Plains Veterinary Educational Center antibiotic resistance mechanisms Decrease Cell Wall Uptake / Perm –Aminoglycosides Efflux –Macrolides, fluoroquinolones, tetracyclines Enzymes Induced –Aminoglycosides, florfenicol, beta-lactams Altered Target Binding Sites –Ribosome …macrolides, lincosamides –Wall Protein … beta-lactams, glycopeptides –DNA … fluoroquinolones Gene Resistance –Plasmids … b-lact, tetra, macro, linco, fluro, sulfa –Transposons … beta-lactams, glycopeptides –Chromosome … beta-lactams, fluoroquinolones

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15 Great Plains Veterinary Educational Center PK / PD Relationships

16 Great Plains Veterinary Educational Center Antibiotic Movement

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19 Great Plains Veterinary Educational Center FDA CVM Cephalosporin Update

20 Great Plains Veterinary Educational Center Cephalosporin Extralabel Prohibition, April 5, 2012 Response to public’s concern for antibiotic resistance development associated with agriculture use. Applies to cattle, swine, chickens, turkeys Prohibits unapproved dose levels, frequencies, durations or route of administration Prohibits use in species in which it is not approved (does not apply to minor food species) Prohibits use for prevention purposes

21 Great Plains Veterinary Educational Center Griffin’s “prevention” vs. “control” use of antibiotic definition The use of antibiotic (s) for "prevention” apply to situations in which the “animal or group of animals" might be/would be exposed to a disease causing bacterium/bacteria. ANDWhereas the use of antibiotic (s) for "control" would apply to situations in which the “animal or group of animals" have been exposed AND the disease process caused by the bacterium/bacteria as begun in some or all of the group of animals as judged by an understanding of the disease process &/or signs (ex: depression, respiratory aberration, anorexia, etc.) have been observed in animals within the group.

22 Great Plains Veterinary Educational Center Guidance 209 “The judicious use of medically important antimicrobial drugs in food producing animals”, April 11 Focus is not to ban, but on assuring drugs are used judiciously … use is a driver of resistance “Medically Important Drugs”: GFI # 152 … penicillins, tetracyclines, aminoglycosides, macrolides, streptogramins and lincosamides … Not affected: bambermycin, bacitracin, ionophores Phase out none therapeutic (growth promotion) use and phase in veterinary oversight for prevention, control and treatment

23 Great Plains Veterinary Educational Center Draft Guidance 213 … “Road Map” of how to attain guidance 209, including a timeline, April 11, 2012 GFI # 152: relative importance to medical community and the duration of use Remove growth promotion from all antibiotics Prevention use must be targeted at defined at-risk population (timing), a defined dosing duration & effective dosing levels Implementation three year target for phasing in changes … Implement revised VFD requirements

24 Great Plains Veterinary Educational Center Veterinary Feed Directive (VFD) … target the movement of OTC to Rx or VFD VFD requirements will be changed … to become less onerous on veterinarians & to allow access to underserved livestock producers Redefine: VFD form, VFD transmission, VFD record requirements & VFD VCPR requirement Category 1 not withdrawal, Category 2 those with a withdrawal Broaden(more flexible) animal identification requirement, number of animal, amount of feed, & expiration of VFD (up to six months) VCPR (current 21 CFR 530)... to … “veterinarian may only issue a VFD for use in animals under their supervision or oversight in the course of their professional practice, and in accordance with all applicable veterinary licensing and practice requirements”

25 Great Plains Veterinary Educational Center What Those of Us Who Are Not Pharmacologist Need To Know About Selection & Use of Antibiotics The objective will be to help better understand: 1) how viruses and bacteria cause different diseases 2) how the antibiotics they use work 3) antibiotics role in treating diseases caused by different bugs 4) antibiotic classes … and what makes them different 5) why an antibiotic seems to work on some cattle & not others 6) how the other things we give sick cattle can influence an antibiotic's effectiveness 7) how to select a proper antibiotic for different diseases 8) how to know when to switch 9) which antibiotic would make a better choice when you need to switch if an animal doesn't respond 10) when to quit http://gpvec.unl.edu 25

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27 why an antibiotic may seem to work on some sets of cattle and not others Source, Source, & Source BIGGEST FACTOR … TIMING!!! –How much of a head start ??? Animal’s ability to help fight back Differences in bugs … Diagnosis ???

28 Great Plains Veterinary Educational Center Select appropriate high quality products Most commonly, BRD has a head start in high- stressed young commingled cattle.

29 Great Plains Veterinary Educational Center Prevention … is key Treatment salvages only part of the loss Immune preparation Treatment timing

30 Great Plains Veterinary Educational Center Vaccine Titers

31 Great Plains Veterinary Educational Center Dealing With Disease Don’t let your thermometer do your thinking! Appetite & Depression

32 Great Plains Veterinary Educational Center Finding Sick Cattle … Number one rule:...Have plenty of time early every morning........ If the temperature is going to be over 70-80 F that day...... Be finished by 10AM RELOOK AT CATTLE OFTEN

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34 how the other things we give sick cattle can influence an antibiotic's effectiveness The stress caused by some products does more damage than their benefit –Injection site irritation ??? –Restraint for IV injection … IV-ing ability Product interferes with antibiotic –Sulfa’s and folic acid (a “B” vitamin)

35 Great Plains Veterinary Educational Center “May Help … What It Don’t Hurt”

36 Great Plains Veterinary Educational Center how to select a proper antibiotic for different diseases … will focus on BRD Pneumonia … Ab penetration not as much of a problem early as late Bugs that live in cells … need Ab that crosses cell walls Animal’s that are over whelmed & can’t help the drug by fighting back … –cidal Ab may be better than static Ab Can’t defend the use of Pen G (especially LA Pen) & Sulfa in BRD Rx programs CAUTION – Generics …& AVOID Bathtub mixes Neomycin & Gentamicin … violate BQA & reason

37 Great Plains Veterinary Educational Center how to know when to switch 1 st … and very important … assess the “stress” effect of the Ab –gut fill, soreness, tissue temp, etc –don’t switch because of stress effect Monitor animal NOT temp!!! –Don’t let the thermometer do your thinking –Use temp to confirm your visual assessment Give the Ab 48 hours … @ MIC 90

38 Great Plains Veterinary Educational Center which antibiotic would make a better choice when you need to switch … poor response Re-check the diagnosis … –& evaluate the treatment extras being used Use previous lab work … –animals that die may be the most valuable If the infection is winning … get meaner –Cidal Ab KILL bugs … good selection –Ab that penetrate … good selection –Ab that minimizes stress effect … may be good Have faith in the treatment plan … stick to it !

39 Great Plains Veterinary Educational Center when to quit Consider two things … 1) How long ago did the “stress” start ??? Auction market … days received + 3 days 2) How long have you been treating animal? QUITIf 1 is over 21 days & 2 is over 7 days … QUIT QUITIf 2 is greater than 10 … QUIT

40 Great Plains Veterinary Educational Center Letting go Giving up on a sick animal that has failed to recover is one of the toughest things we ask our treatment crew to do. Medications given to sick cattle that repeatedly fail to respond are extremely expensive. Recognizing when it is time to stop therapy is tough, but simple rules for when to stop must be developed and enforced.

41 Great Plains Veterinary Educational Center Letting go Total cost of therapy may be a good guideline, but should be included with decisions based on the number of therapy days. Management should evaluate continue therapy on all sick cattle that fail to respond with in seven days.

42 Great Plains Veterinary Educational Center why an antibiotic may seem to work on some sets of cattle and not others Source … Immune prep history Source … Nutritional history Source … Stress & Commingling BIGGEST FACTOR … TIMING!!! How much of a head start ??? Animal’s ability to help fight back Differences in bugs … Diagnosis???

43 Great Plains Veterinary Educational Center Prevention … is key Treatment salvages only part of the loss Immune preparation Treatment timing

44 Great Plains Veterinary Educational Center Dealing With Disease Don’t let your thermometer do your thinking! Appetite & Depression 44

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46 Great Plains Veterinary Educational Center Finding Sick Cattle … Hit the bulls eye with … DART  Depression  Appetite  Respiration  Temperature & never let the thermometer do your thinking!

47 Great Plains Veterinary Educational Center Finding Sick Cattle … Number one rule:...Have plenty of time early every morning.... If the temperature is going to be over 80 F that day...... Be finished by 10AM RELOOK AT CATTLE OFTEN

48 Great Plains Veterinary Educational Center how to select a proper antibiotic for different diseases … will focus on BRD Pneumonia … Ab penetration not as much of a problem early as late Bugs that live in cells … need Ab that crosses cell walls Animal’s that are over whelmed & can’t help the drug by fighting back … –cidal Ab may be better than static Ab Can’t defend the use of Pen G (especially LA Pen) & Sulfa in BRD Rx programs CAUTION – Generics …& AVOID Bathtub mixes Neomycin & Gentamicin … violate BQA & reason

49 Great Plains Veterinary Educational Center how to know when to switch 1 st … and very important … assess the “stress” effect of the Ab –gut fill, soreness, tissue temp, etc. –don’t switch because of stress effect Monitor animal NOT temp!!! –Don’t let the thermometer do your thinking –Use temp to confirm your visual assessment Give the Ab 48 hours … @ MIC 90

50 Great Plains Veterinary Educational Center which antibiotic would make a better choice when you need to switch … poor response Re-check the diagnosis … –& evaluate the treatment extras being used Use previous lab work … –animals that die may be the most valuable If the infection is winning … get meaner –Cidal Ab KILL bugs … good selection –Ab that penetrate … good selection –Ab that minimizes stress effect … may be good Have faith in the treatment plan … stick to it !

51 Great Plains Veterinary Educational Center Letting go Giving up on a sick animal that has failed to recover is one of the toughest things we ask our treatment crew to do. Medications given to sick cattle that repeatedly fail to respond are extremely expensive. Recognizing when it is time to stop therapy is tough, but simple rules for when to stop must be developed and enforced.

52 Great Plains Veterinary Educational Center Letting go Total cost of therapy may be a good guideline, but should be included with decisions based on the number of therapy days. Management should evaluate continue therapy on all sick cattle that fail to respond with in seven days.

53 Great Plains Veterinary Educational Center when to quit Consider two things … 1) How long ago did the “stress” start ??? Auction market … days received + 3 days 2) How long have you been treating animal? QUITIf 1 is over 21 days & 2 is over 7 days … QUIT QUITIf 2 is greater than 10 … QUIT It seems to me, we should see visible improvements in attitude & appetite within 96 hrs with the long T1/2 antibiotics … 53

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55 http://gpvec.unl.edu Dgriffin@GPVEC.UNL.EDU 55

56 Great Plains Veterinary Educational Center Responsible Use Considers RESIDUE AVOIDANCE 56

57 Great Plains Veterinary Educational Center Antibiotic Resistance & Residue Concerns … Fuel the winds of change HR 1549 & S619 … “PAMTA” example: HR 1549 & S619 … “PAMTA” “Preserve Antibiotics for Medical Treatment Act” Targets ‘ Nontherapeutic Use’ “ with respect to a critical antimicrobial animal drug, means any use of the drug as a feed or water additive for an animal in the absence of any clinical sign of disease in the animal for growth promotion, feed efficiency, weight gain, routine disease prevention, or other routine purpose.’ ‘(A) any kind of penicillin, tetracycline, macrolide, lincosamide, streptogramin, aminoglycoside, or sulfonamide; or (B) any other drug or derivative of a drug that is used in humans to treat or prevent disease or infection caused by microorganisms.’ 57

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59 Great Plains Veterinary Educational Center Flunixin Injection Sites … Ouch, This Has Got to HURT! Why do we use flunixin? –Reduce Inflammation –Make them feel better? How could causing this much tissue damage make them feel better? Can’t give it IV … Considering the adverse effect … if it can’t be given IV why not skip its use 59

60 Great Plains Veterinary Educational Center The National Residue Program (NRP) consists of two sampling plans: domestic &import. The domestic sampling plan includes … Scheduled Sampling & Inspector Generated Sampling Scheduled sampling plans consist of the random sampling of tissue from healthy appearing food animals Statistically, applying sampling rates of 230 & 300 per production class population assures a 90 percent and 95 percent probability, respectively, to detect residue violations if the violation rate in the population is equal to or greater than one percent. 60

61 Great Plains Veterinary Educational Center The National Residue Program (NRP) consists of two sampling plans: domestic &import. The Tolerance or Maximum Residue Limit (MRL) for each class of compound are listed in: – Title 21 CFR for FDA regulated compounds – Title 40 CFR for EPA regulated compounds 61

62 Great Plains Veterinary Educational Center The National Residue Program (NRP) consists of two sampling plans: domestic &import. Inspector generated sampling is conducted by in-plant Public Health Veterinarians (PHVs) This occurs when the in-plant PHV suspects that an animal may have violative level of chemical residues. Targets “ individual suspect animals and suspect populations of animals.” – Individuals: Target injection sites & animals with active infections that could reasonably be suspected as having been recently treated. – Populations: History of residue violations 62

63 Great Plains Veterinary Educational Center USDA-FSIS Changes Residue Screening Test In October 2008, the USDA Food Safety and Inspection Service (FSIS) awarded Charm Sciences a contract to provide Charm KIS Tests to USDA inspectors at slaughter facilities to screen for sulfonamides and antibiotic drugs under the National Residue Program (NRP). FSIS will begin implementing the Charm KIS Test in phases starting with cattle (FSIS notice 50-90) and eventually implement it for all livestock. 63

64 Great Plains Veterinary Educational Center Total Cattle Marketed 64

65 Great Plains Veterinary Educational Center Residues … Flunixin

66 Great Plains Veterinary Educational Center Residues … Sulfas

67 Great Plains Veterinary Educational Center Residues … Sulfas

68 Great Plains Veterinary Educational Center Residues … What were they thinking?

69 Great Plains Veterinary Educational Center Residues … beta lactams

70 Great Plains Veterinary Educational Center Residues … OTC vs Vet Rx 70

71 Great Plains Veterinary Educational Center Chemical Defects … Residues 1982, just under 2% of all beef cattle 2010, random samples: Zero antibiotics 71 High Risk TARGETED Samples have residue rates that are very low! … BEEF IS BEEF … & 0.000 positive % … IS NOT ZERO

72 Great Plains Veterinary Educational Center Flunixin Residues: Flunixin ELDU … leading to residues – The Center for Veterinary Medicine Reminds Veterinarians to Correctly Use Flunixin Meglumine (FDA Veterinarian Newsletter 2007, Volume XXII, Number 11) – FARAD, Flunixin WD… IM administration requires 30 days for single injection … 60 days for multiple IM injections … WD of SC flunixin meglumine in cattle cannot be established. (JAVMA 232(5):697-701, 2008.) 72

73 Great Plains Veterinary Educational Center Ceftiofur … Under Pressure! Ceftiofur … approved for cattle in 1988 20 years with no residues listed in USDA-FSIS “Red Book” reports (these are yearly residue testing reports). FDA announced elimination of ELDU, July 2008, but amended ELDU ban after comment period evaluation. ( 2/3 in cull dairy cows associated with producers not following the prescribed usage, dosing or withdrawal time) Dr Flynn (FDA) announced ceftiofur residues at KSU meeting May 2009 … communications suggest a significant number of violative residues in 2008, … perhaps associated with test methodology changes … ( 2/3 in cull dairy cows associated with producers not following the prescribed usage, dosing or withdrawal time) Would “Cow-side”, residue screening help? Would “Cow-side”, residue screening help? 73

74 Great Plains Veterinary Educational Center June 2007 Vet Survey Materials & Methods (June 2007) Postal survey (within AABP newsletter) 27 questions – Demographics (6) – Treatment Strategies (12) – Client Communication (4) – Dairy Beef Quality Assurance Programs (5) 74

75 Great Plains Veterinary Educational Center “How often do you look at your clients written treatment records?” June 2007 75 Vet Survey Materials & Methods (AABP, June 2007) 75

76 Great Plains Veterinary Educational Center “How often do you think producers will not comply with instructions & will cause a violative residue?” June 2007 76 Vet Survey Materials & Methods (AABP, June 2007) 76

77 Great Plains Veterinary Educational Center Ceftiofur Residues … “The Most Probable Cause” Ceftiofur Na… the “zero” withdrawal antibiotic (CM = 14 ug/ml, T½ =10hrs, MRL= 8ug/ml) … this led to “ownership” of the dairy market … this led to “ownership” of the dairy market MRL lowered to 0.4 ug/ml … WD to 4 days MRL lowered to 0.4 ug/ml … WD to 4 days Ceftiofur HCl and CCFA … – similar change in WD math Producers not respecting new WD times Producers not respecting new WD times – record monitoring vigilance important 77

78 Great Plains Veterinary Educational Center RESIDUE AVOIDANCE … Carefully evaluate your ELDU & the extended withdrawals you assign. … Review treatment & marketing records to assess prescription compliance. 78

79 Great Plains Veterinary Educational Center Antibiotic Residue Avoidance Strategy Identify all animals treated. Record all treatments: Date; animal’ ID; dose given; route of administration; the person who administered the treatment; withdrawal time (WD). Strictly follow label directions for product use. Use newer technology antibiotics when possible. Select antibiotics with short WD when the choice is equivalent. Never give more than 10 cc per IM injection site. Avoid Extra Label Drug Use (ELDU) of antibiotics. Avoid using multiple antibiotics at the same time. Don’t mix antibiotics in the same syringe. Check ALL medication/treatment records before marketing. 79

80 Great Plains Veterinary Educational Center What can be done to protect our producers … & ourselves? Use residue screening tests such as the urine adapted PremiTest or PHAST before “high-residue-risk” cattle are sold …Use residue screening tests such as the urine adapted PremiTest or PHAST before “high-residue-risk” cattle are sold … Will the test work “pre-harvest”? – Yes … BUT it is a microbial inhibition test and must use with knowledge of the sensitivity & the MRL If the urine doesn’t inhibit the test … it is not likely tissue juices from the kidney will inhibit the test … a couple of potential exceptions … Gen & Neo PremiTest (DSM Corp), PHAST (Pre-Harvest Antibiotic Screening Test) 80

81 Great Plains Veterinary Educational Center Testing Urine Isn’t Tough … (Pre-Harvest Antibiotic Screening Test) 81

82 Great Plains Veterinary Educational Center PHAST ( B. meg. FAST used on urine) “This little cow gets to go to Market” “This little cow stays home” 82

83 Great Plains Veterinary Educational Center B. stearothermophilus DSM PremiTest, Charm KIS, 147 ⁰ F (64 ⁰ C) for 3 hrs 83

84 Great Plains Veterinary Educational Center 84 All positive screening tests are confirmed by approved analytical methods in an FSIS laboratory 84

85 Great Plains Veterinary Educational Center What is the most important position our profession & industry can have? DON’T SEND CATTLE TO MARKET WITH A RESIDUE! 85

86 Great Plains Veterinary Educational Center 86 In the world of food Consumers Purchase BUY BUY WHAT WHAT THEY THEY TRUST TRUST 86


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