1. Great Plains Veterinary Educational Center What You Need to Know &Think About When Selecting Antibiotics The objective will be to help folks better understand: 1) how antibiotics work … clinically 2) antibiotic classes … & what makes them different 3) how to think through developing treatment protocols 4) understand dose management & resistance development 5) how to select a proper antibiotic for different diseases 6) how the other things given sick cattle can influence an antibiotic's effectiveness 7) how to know when to switch 8) which antibiotic would make a better choice when a switch is need if an animal doesn't respond 9) when to quit 10) potential residue considerations & management

2. Great Plains Veterinary Educational Center Parts of the Puzzle

3. Great Plains Veterinary Educational Center IBR at work

4. 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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7. 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.

8. 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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11. 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 …

12. 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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16. Great Plains Veterinary Educational Center PK / PD Relationships

17. Great Plains Veterinary Educational Center Antibiotic Movement

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21. Ab Use & Testing … Think About It

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23. 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???

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

25. Great Plains Veterinary Educational Center Dealing With Sick Cattle

26. Great Plains Veterinary Educational Center Dealing With Disease Don’t let your thermometer do your thinking! Appetite & Depression 26

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28. 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!

29. 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

30. 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

31. 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

32. 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 !

33. Great Plains Veterinary Educational Center Cephalosporin Note

34. 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

35. 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.

36. Great Plains Veterinary Educational Center NEW Feed Antibiotic Use Regulations

37. Great Plains Veterinary Educational Center FDA antibiotic resistance potential grid (GFI 152)

38. Great Plains Veterinary Educational Center FDA antibiotic resistance potential grid (GFI 152) Not ALL compounds classified as ANTIBIOTICS are IMPORTANT

39. Great Plains Veterinary Educational Center FDA antibiotic resistance potential grid (GFI 152) Not ALL compounds classified as ANTIBIOTICS are IMPORTANT 1/3 of ALL USE

40. Great Plains Veterinary Educational Center FDA antibiotic resistance potential grid (GFI 152)

41. Great Plains Veterinary Educational Center FDA antibiotic resistance potential grid (GFI 152)

42. Great Plains Veterinary Educational Center FDA antibiotic resistance potential grid (GFI 152) ONLY for DISEASE ONLY if VETERINARY Supervision

43. Great Plains Veterinary Educational Center FDA developed an antibiotic resistance potential grid (GFI 152) In addition to GFI 152 … No future approvals for “production purposes” Production purposes means – “improved growth or gain” or – “improved feed efficiency” or – “improved reproductive efficiency”

44. Great Plains Veterinary Educational Center FDA antibiotic feed use approval would be ONLY for DISEASE » Treatment » Prevention » Control Go To

45. Great Plains Veterinary Educational Center What’s are livestock raisers giving up? … NOTHING !.

46. Great Plains Veterinary Educational Center Not as many labels as you might think

47. Great Plains Veterinary Educational Center What will the new labels looks like?

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50. nnnnnnn nnnnnnn Tetracyclines have been 60% of all use NEVER AGAIN

51. Great Plains Veterinary Educational Center … we MAY GET a few … we MAY GET a few new feed antibiotic usages that are much more effective for prevention, treatment or control of disease than are currently available.

52. Great Plains Veterinary Educational Center What do you need to use a VFD? … A working relationship with your veterinarian(s)

53. Great Plains Veterinary Educational Center VCPR Vet assumed responsibility for making clinical judgments, need for treatment, and the client has agreed to follow the veterinarian's instructions. Veterinarian has sufficient knowledge to initiate preliminary diagnosis. Meaning has recently seen & personally acquainted with keeping & care via exam or medically appropriate & timely visits. The veterinarian is readily available for follow-up evaluation in the event of adverse reactions or failure of the treatment regimen.

54. Great Plains Veterinary Educational Center VCPR … VFD Clarifications Veterinarian must be licensed in the state in which the cattle reside Veterinarian is not required to make the disease diagnosis … BUT … is responsible for developing the disease diagnosis protocol AND is responsible for training the people that will make disease diagnosis Feedlot management must be willing to abide by their licensed veterinarian’s BRD diagnosis protocol and use of the VFD

55. Great Plains Veterinary Educational Center VFD … Caution Statement Reminder … Extra-Label Use of any FDA approved feed additive is strictly prohibited. VFD drugs must be fed in the manner dictated on the VFD drug approval

56. Great Plains Veterinary Educational Center VFD Form Requirements Vets name, address, telephone number, license number & State issued, Client's name, address, & telephone number, Species & # animals treated, Animal’ identification numbers/descriptions, … Animals' location, Date of treatment & the date the VFD order is issued, Name of animal drug, Drug's approved or index-listed use indications. Level of drug in the feed and amount of feed required to treat animals, Feeding instructions, … Withdrawal time (if applicable), Any special instructions & caution statements, Order's expiration date, Number of refills (reorders) permitted by the drug's approval regulation, The following statement verbatim: "Extra-label use (i.e., use of this VFD feed in a manner other than as provided for in the VFD drug approval) is strictly prohibited", and any other information that the VFD drug's approval regulation requires you to include on the form.

57. Great Plains Veterinary Educational Center Pulmotil … “Micotil in a Bag” VFD … EXAMPLE

58. Great Plains Veterinary Educational Center Pulmotil VFD Pulmotil is approved for “control” not mentioned is “prevention” or “treatment” “ORDER”Similar to the prescription requirement for injectable products, a veterinarian must issue an FDA-required Veterinary Feed Directive (VFD) … “ORDER” The VFD process requires a coordinated effort by the producer, veterinarian, nutritionist & feed mill Activity Appropriateness * Prevention, disease has not been diagnosed ** Control, disease has been diagnosed in group *** Treatment, to deal with active disease

59. Great Plains Veterinary Educational Center Pulmotil Indication for Use control For the control of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, & Histophilus somni a 14 day therapy during 1 st 45 DOF (can’t start after 32 DOF) … in groups of beef and non-lactating dairy cattle, where active BRD has been diagnosed in at least 10% of the animals in the group … Who does the diagnosing.,. The producer following the vets diagnosing protocol Pulmotil withdrawal is 28 days

60. Great Plains Veterinary Educational Center “BRD Dx at least 10% of the animals in the group” Responsibility for developing the BRD Dx protocol / Dx SOP is the sole responsibility, based on their clinical experience and judgment, of the veterinarian with the “Valid VCPR” for the cattle being considered for treatment with the VFD Pulmotil … the diagnosis protocol must be on file at the producers

61. Great Plains Veterinary Educational Center “BRD Dx at least 10% of the animals in the group” What is not required Dx BRD … What is not required … – A direct visual or physical exam by the veterinarian with the Valid VPCR is not required The veterinarian can train feedyard personnel to use the BRD Dx protocol / Dx SOP … Training documentation is required – Cattle temperatures are not required to Dx BRD – Necropsy diagnosis is not require from an animal within group being considered

62. Great Plains Veterinary Educational Center “BRD Dx at least 10% of the animals in the group” What can be used Dx BRD … What can be used … – The “DAR”* of the “DART” system (Depression, Appetite, & Respiration)* BUT other Dx criteria can be developed as, in the judgment of the responsible vet, are appropriate.

63. Great Plains Veterinary Educational Center VFD & Injectable Antibiotics The treatment should not occur concurrent with or following administration of an injectable macrolide, Or within 3 days following administration of a non-macrolide injectable BRD therapy.

64. Great Plains Veterinary Educational Center Pulmotil is not intended for use in Cattle with Severe Clinical Disease individual treatment with an alternative non-macrolide therapy.” While feeding Pulmotil, “cattle with severe clinical illness should be evaluated for individual treatment with an alternative non-macrolide therapy.” After treatment, these cattle can return to their group

65. Great Plains Veterinary Educational Center Pulmotil VFD example calculations A Pulmotil 5.68g/lb pellet is available & pellets mix well in high wet distillers feeds Use calculations are based on Pulmotil’s approved Type C dose range of 568 to 757 g/ton tilmicosin (100% DMB) within the DMI range of 1.5 to 2% of body weight (BW). all this LOOKS complicated … but it’s not Tilmicosin dose: 12.5 mg/kg of BW/hd/d = 5.68 mg/lb of BW/hd/day … all this LOOKS complicated … but it’s not 1 lb of 5.68g/lb pellet will dose 1,000 lbs of cattle BUT … must be fed as the sole feed!!!

66. Great Plains Veterinary Educational Center Pulmotil VFD example calculations Feed intake restriction is a serious issue with using Pulmotil The FDA restricts its use only to cattle eating between 1.5% & 2.0% of the body weight (DMB) of feed Total feed for a 14 day therapy … Ex: 100 steers avg. 500 lbs expected DMI 2% BW = 10lb/day 10 x 14 = 140 lbs … x 100 head = 14,000 lbs Total lbs of 5.68g/lb pellet needed … 1 lb pellet / 1000 lb cattle / daily dose 100 head X 500 lbs = 50,000 / 1000 = 50 lbs pellet / day 50 lbs pellet x 14 days = 700 lbs pellets needed Vet, Producer & VFD med supplier (feed mill) all keep copy of VFD for 2 years

67. Great Plains Veterinary Educational Center Pulmotil (Micotil in a Bag) Problem: Fill out VFD for the above example … above