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. 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???

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

23. Great Plains Veterinary Educational Center Dealing With Sick Cattle

24. Great Plains Veterinary Educational Center Dealing With Disease Don’t let your thermometer do your thinking! Appetite & Depression 24

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26. 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!

27. 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

28. 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

29. 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

30. 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 !

31. Great Plains Veterinary Educational Center FDA CVM Update

32. 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

33. 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.

34. 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

35. 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

36. 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”