An Overview of Antibiotic Usage in South Dakota Livestock:

A Veterinarian’s PerspectiveSept. 11, 2019

Darrel Kraayenbrink DVM, MPH, DACVPM

Reasons for Antibiotic Use in Livestock

1. Treatment of disease in animals or herds (therapeutic)

2. Control of disease known to be present in the herd

3. Prevention of disease at risk of occurring (prophylactic/metaphylactic use)

Classification of Common Livestock Antimicrobials• ** Fluoroquinolones: enrofloxacin, danofloxacin

• ** Macrolides: tildipirosin, tilmicosin, tylosin, tulathromycin, gamithromycin

• * Lincosamides: lincomycin, pirlimycin

• ** Cephalosporins: ceftiofur (third generation), cephaparin

• * Penicillins: penicillin, amoxicillin, ampicillin

• * Tetracyclines: oxytetracycline, chlortetracycline, doxycycline

• * Aminoglycosides: neomycin

• Phenicols: florfenicol

• Sulfonamides: sulfamethizine, sulfadimethoxine,

• ** Potentiated Sulfas: Trimethoprim/sulfamethoxazole

• Ionophores: lacolid, monensin

* highly medically important antibiotic class

** critically medically important antibiotic class

Antibiotic modes of action

Bacteriostaticsuppress the pathogen, allow immune system time to work, longer duration

• Draxxin

• Micotil

• Zactran

• Zuprevo

• Nuflor

• Oxytetracyclines (LA200, LA300)

Bactericidalkills the pathogen, higher concentration,

shorter duration

• Baytril

• Excede

• Excenel

• Penicillin

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Considerations in Choosing a Therapeutic Antibiotic for Livestock

• Efficacy vs the pathogen(s) involved

• Cost

• Convenience of use

• Previous experience and comfort level

• Spectrum of activity: broad spectrum vs narrow

• Classification as medically important

• Duration of effect

• Post-treatment interval

Post Treatment Intervals (PTI)

• Voluntary time period after an antibiotic treatment when no other antibiotics will be used

• The time it takes to determine treatment success or failure following an antibiotic treatment

• Saves time, labor, drug expense; take full advantage of drug duration of therapy for expensive drugs

• Use industry standards for setting PTI, PTI studies are ongoing

• See attached Antibiotic spreadsheet for common PTI values6

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Antibiotic Comparison - Cattle BRD (2019)

Drug Drug Class Dosage Max/site Duration PTI ¹

Withdra

wal Dose Cost ² Advantages Disadvantages

METAPHYLAXIS/

TREATMENT 600 lb calf example

Draxxin ℞ Macrolide 1.1cc/100 lb SQ 10cc 14 days 10 18 day 6.6cc $26.77Low dose, good duration, also approved 12 hours until optimal lungfor PE, footrot, Mycoplasma³ concentration, higher cost

Micotil ℞ Macrolide 1.5cc-3cc/100 lb SQ 10cc 10 days 4 42 day 9cc - $14.38 Low dose, lower cost Personal safety risk ⁴, long

18cc - $28.76 flexible dosingwithdrawal, less effective for BRD

Zactran ℞ Macrolide 2cc/110 lb SQ 10cc 10 days 10 35 day 11cc $17.94Fast-acting (30 min.) good durationMycoplasma³

Zuprevo ℞ Macrolide 1cc/100 lb SQ 10cc 21-28 days 10 21 day 6cc $25.23 Fast-acting (45 min),low dose Higher cost

Hexasol ℞ Tetracycline 4.5cc/100 lb SQ 10cc 7 days 4 21 day 27cc $4.98 Includes fever reducer Higher dosealso good for footrot less effective for BRD

Oxytet300 Tetracycline 4.5cc/100 lb SQ 10cc 7 days 4 28 day 27cc $4.38 Longer duration, less cost Less effective for BRD, lesssyringable, higher dose

TREATMENT

Advocin ℞ F.quinolone 2cc/100 lb SQ 15cc Conc.Dep. 3 4 day 12cc $18.62 Fast-acting, low dose, Not approved for H.somnusshort withdrawal

Baytril ℞ F.quinolone 5cc/100 lb SQ 20cc Conc.Dep. 3 28 day 30cc $16.78 Fast-acting, Mycoplasma³ Higher dose

Excede ℞ Beta-lactam 1.5cc/100 lb Ear 7 days 5 13 day 9cc $16.97 Low dose Inconvenient injection site,slower acting, less syringable

Excenel ℞ Beta-lactam 2cc/100 SQ 15cc 2 days 2 4 day 12cc $9.54Short slaughter withdrawal, low cost Short duration, 2nd dose

recommended, less syringable

Nuflor ℞ Florfenicol 6cc/100 lb SQ 10cc 4 days 3 38 day 36cc $25.02 Longer duration Higher dose, less syringableMycoplasma³ long withdrawal time

Bovine Respiratory Disease (BRD)

• Bovine Respiratory Disease (BRD or shipping fever) is the most significant economic disease of feedlot cattle

• BRD is multifactorial: transport stress, immune deficiency, viral and bacterial pathogens; Mannheimia haemolytica is predominant, Pasteurella multocida, Histophilus somni and Mycoplasma bovis are also associated with pneumonia

• Bovine lungs are very small relative to the animal’s

oxygen requirements

• The total lung capacity of an adult cow is only 2.5 times

greater than that of an average man, yet its resting oxygen requirement is more than 10 times greater

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BRD treatment guidelines

• No more than 3 treatments per case of BRD following metaphylaxis PTI; there’s no data to show any economic benefit for >4 treatments

• Use a bactericidal drug for initial treatment after metaphylaxis

• For repulls use another non-macrolide drug (if metaphylaxisgiven)

• Final treatment use LA300 or penicillin +/- dexamethasone

• Plan your treatment protocol and stick to it if possible

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Metaphylaxis Principles

• Mass medication during disease incubation period to cattle at high risk of becoming sick from BRD

• Macrolides best: 7-12 day antibiotic coverage

• Draxxin, Micotil, Zactran, Zuprevo

• Consider drug cost ($15-30/head) vs risk of potential BRD cost

• Can be used at initial processing on arrival, or after a certain preset threshold is reached, E.g. after 25% calves have been pulled for BRD treatment

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What is Metaphylaxis Worth to the Industry?

• $1.8 billion/year for high risk cattle according to recent Kansas study

• Used by 59% of US feedlots on 20% of all cattle placed on feed

• Reduced revenues would come from reduced ADG, increased FC, higher health costs, higher death loss

• Revenue losses compared for 3 calf weight classes: 550 lb (-$104/hd), 700 lb (- $99/hd), 850 lb (- $64/hd)

• Full article online at bit.ly/KSUmetaphylaxisstudy

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Feedlot Calf Health Risk Assessment

Low Risk• Single source, ranch direct• Weaned• Bunk and water broke• Preconditioned: vaccinated and

boostered• Short haul• Northern cattle

High Risk• Not weaned• Salebarn• Multiple sources (>5 = very high)• Stale (>3 days to comingle=very

high)• Unvaccinated• Long haul (>12 hours)• Southern cattle• Lightweight or >200 lb variation• Bulls or pregnant heifers

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Sample Calf BRD Treatment Protocols

A. Low risk: 500 lb. single ranch source, no sale barn, preconditioned

Metaphylaxis: probably not necessaryFirst treatment: Baytril 25 cc SQ, 3 day PTI

Second treatment: Nuflor 30 cc SQ, 4 day PTI

Third treatment: LA300 20 cc SQ

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Sample Calf BRD Treatment Protocols

B. High risk calves: 500 lb not weaned, 5 sources, purchased through a salebarn, Southern origin

Metaphylaxis: Draxxin 5.5 cc SQ, 10 day PTI

First treatment: Baytril 25 cc SQ, 3 day PTI

Second treatment: Nuflor 30 cc SQ, 4 day PTI

Third (final) treatment: LA300 20 cc SQ

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Whisper Veterinary Stethoscope System

• Merck Animal Health, currently being tested in large feedlots

• determine which animals actually need treatment and support judicious antibiotic use

• Whisper is placed on the animal’s chest wall. In eight seconds, it computes a lung severity scale from 1-5

• Improves accuracy of BRD diagnosis and could provide for “targeted metaphylaxis” for incoming high-risk calves

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Determining Treatment Success

• Response to treatment may require patience during the PTI, don’t be too quick to retreat

• If symptoms of BRD worsten > 24 hr: depression, appetite loss (gaunt), rapid or difficulty breathing, calf may need to be pulled during the PTI and retreated, especially if fever > 104*

• If over 10% require retreatment during PTI other complications may be involved

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Advantages in Using Macrolides to Treat BRD

• Draxxin (tulathromycin), Micotil (tilmicosin), Zuprevo (tildipirosin)or Zactran (gamithromycin)

• Macrolides have good efficacy against BRD pathogens, long duration, low dose convenience (only 1-2 cc/100 lbs. BW), and generally effective vs Mycoplasma pneumonia (generally resistant to other classes of antibiotics)

• Long duration (14-21 day drug therapeutic levels) with one injection has major advantages: 1. labor saving, eliminate the need to retreat; 2.valuable for metaphylaxis during high risk periods (e.g. incoming newly weaned or comingled calves)

• Low-dose convenience, especially for dart guns

Methods of Antibiotic Delivery in Livestock

• Injectable

• Orally through drinking water

• Orally through medicated feed

Injectablemedications are given intra-muscular or subcutaneously using BQA or PQA guidelines for proper injection technique; also remote injection systems (dart guns)

Orally through drinking water

• either added directly to water tank or through a medicatorwhich siphons the drug from a stock solution into the drinking water line

• Water medications require a prescription to be used, as of Jan 1, 2017

Water Medications I commonly prescribeCattle

• Sulfadimethoxine: 5 days for control of BRD outbreak

• * Tetracycline: also 5-days for BRD

Swine

• Sulfadimethoxine: respiratory disease

• * Oxytetracyline: respiratory disease

• * Amoxicillin: Streptococcal/ Haemophilus parasuis infections (nursery pigs)

• Tiamulin (Denagard): for treatment and control of swine ileitis and swine dysentery- Pleuromutilin class, current research on human antibiotics also

* medically important

Orally through medicated feed• An antibiotic premix is either added to the complete ration or top-

dressed by hand over the bunk ration

• Feed medications (for medically important antibiotics) require a VFD (Veterinary Feed Directive) as of Jan 1, 2017

Feed Antimicrobials Commonly Used in My Clients’ Herds

Cattle

• Ionophores: Rumensin (monensin), Bovatec (lacolid) -improve feed efficiency, some gut health improvments(coccidiosis)-class not used in human medicine

• *Tetracyclines: Aureomycin (chlortetracycline) crumbles or premix-therapeutic levels for herd treatment (10 mg/lb for 5 days)

• *Tylosin (Tylan): macrolide, used in late finishing phase to prevent liver abscesses due to low grade acidosis

*medically important, requires VFD (feed Rx)

Common Feed Antimicrobials (cont.)Swine• *Tetracyclines: Aureomycin (chlortetracycline) 10 mg/lb. for 14 days

for bacterial pneumonia• Tiamulin (Denagard): for treatment and control of swine ileitis and

swine dysentery• Carbadox (Mecadox): control of swine dysentery, class not used in

humans• *Tylosin (Tylan): macrolide, used to control swine dysentery• Lincomycin (Lincocin): arthritis/certain pneumonias, not used in

humans• *Tilmicosin (Pulmotil): macrolide, swine respiratory disease

*medically important, requires VFD (feed Rx)

Remote Injection Systems (dart guns)

Breach loading air rifle, either pneumatic or CO2 poweredCapable of delivering 0.5-10cc

of medication (antibiotics or tranquilizers)

Range of 1-20 yards

Advantages to Remote Injections

• Labor and time savings

• Less animal handling/stress

• Ability to treat pasture cattle early for better response

• Increased margin of safety for animal and animal handler

Disadvantages to Remote Injections

• Potential Beef Quality Assurance issues

• Requires ELDU (extra-label drug use)

• Added treatment cost (low dose, expensive macrolide antibiotics)

• Training required to safely operate a dart gun

Draxxin administration via Dart Guns,University Study

• Researchers at Iowa State and Texas A&M Universities compared the blood plasma concentrations for several days and meat tenderness at slaughter following delivery of Draxxin via dart gun compared to SQ injection.

• Darts were fired at 25-30 feet using both Pneu-Dart’s pneumatic and C02 powered rifle, 10 cc 14 ga half inch needle.

• In one study 4/15 darts failed to properly fire resulting in low plasma concentrations; plasma levels in other animals were similar to SQ.

• Meat from the darted side in one study was less tender than non-darted side.

• Conclusion: darts were not a consistently reliable method of delivery.28

Other common indications for Antibiotic use in Cattle: Bovine pinkeye (keratoconjunctivitis)

• Caused by Moraxella sp bacteria, Mycoplasma

• Conjunctivitis leading to severe ulcerative cornea

• Very painful, contagious

• Commonly treated with tetracyclines, macrolides

Bovine Footrot• Fusobacterium bacterial infection, secondary to interdigital

injuries caused by rough yards, prolonged standing in

water

• Very painful and contagious

• Responds well to antibiotic therapy if treated early:

tetracyclines, penicillin, macrolides

• Foot baths, foot wraps, claw amputations sometimes also used

Actinomycosis (Lumpy Jaw)

• Caused by Actinomyces bovis infection

• Secondary to damage to oral mucosa from coarse hay, weed awns, leading to a chronic, progressive, granulomatous abscess

• treatment is IV sodium iodide, and/or antibiotics (penicillin,

tetracycline or florfenicol); sometimes drainage or debridement also used

Enterotoxigenic E. coli diarrhea (K99)• Newborn calves up to 7 days old

• Secretory diarrhea with dehydration, acidosis, rapid death

• Treatment includes fluids and electrolytes, alkalinizing agents, antibiotics only if systemically ill (30% these will be bacteremic)

• Beta-lactams (ceftiofur); amoxicillin or potentiated sulfas orally

Judicious Use Principles - AVMA

• Preventive strategies should be emphasized (hygiene, vaccinations, etc.)

• Rx, VFD or ELDU must meet all requirements of a valid VCPR

• Antibiotics important in treating refractory infections in human or veterinary medicine should be chosen only after careful review and with reasonable justification. Consider using other antibiotics for initial therapy.

• Use narrow spectrum antibiotics whenever possible.

• Use culture and sensitivity results to aid in selecting an antibiotic to use.

• Use only when appropriate, not for uncomplicated viral infections.

• Treat for only as long as necessary.

• Limit treatments to ill or at-risk animals, treating the fewest animals indicated.

• Limit environmental contamination with antibiotics whenever possible.

• Use accurate treatment and outcome records to evaluate treatment regimens.

South Dakota Beef Quality Assurance

SD BQA Program

• A voluntary nationally coordinated, state implemented program supported by the Beef Checkoff program.

• BQA programming focuses on educating and training cattle producers and veterinarians on cattle food safety and quality issues, including judicious use of antibiotics, good preventive care and tools for verifying humane animal husbandry practices.

• Consumers gain confidence in the safety and quality of beef produced under BQA guidelines, resulting in packer demand for BQA-sourced cattle.

• BQA becomes mandatory by default for beef producers in order to gain market access

Management Practice Examples to Decrease Need for Antibiotics

• Age segregation of animal groups (different levels of immunity)-- swine feeding operations-- Sandhills calving system

• All in/all out pig flow

• Targeted vaccination programs using better diagnostics

• Autogenous (farm specific) vaccines

• Optimal nutrition

• Improved ventilation systems

Summary

• Antibiotics continue to be an important tool to maintain livestock health

• Future antibiotic usage will require even greater veterinary oversight (elimination of all OTC labelling?)

• More emphasis on judicious drug use and voluntary quality assurance programs