Alternatives to Antibiotic Use in Calves

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Alternatives to Antibiotic Use in Calves?

• Some Current Research
• Veterinary Continuing Education Program

Photo Courtesy of ACB Berge
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Objectives

• Why should we be concerned about antibiotic
  resistance in animal agriculture?
• What are the factors that govern the development
  of resistance?
• What are some alternatives to using antibiotics
  in pre-weaned calves?

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Ceftriaxone-Resistant Salmonella Infection
Acquired by a Child from Cattle
Paul D. Fey, Ph.D., Thomas J. Safranek, M.D.,
Mark E. Rupp, M.D., Eileen F. Dunne, M.D.,
M.P.H., Efrain Ribot, Ph.D., Peter C. Iwen, M.S.,
Patricia A. Bradford, Ph.D., Frederick J.
Angulo, D.V.M., Ph.D., Steven H. Hinrichs, M.D.
N Engl J Med. 2000 Apr 27342(17)1242-9.

• From NEJM 2000 caused quite a stir
• Really a good link made?
• Led to increased interest in antimicrobial use in
  food producing animals

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Whats the Concern?

• Preventive and low-level (in-feed) use of
  antibiotics in food animals
• incriminated as causes for antibiotic resistance
  in human pathogens (Banned by EU)
• In the US, animal antibiotic consumption volume
  is high
• As a result, antibiotic resistance in bacteria
  from food animals has been monitored on a
  national and local level for several decades

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Why Our Studies?

• Factors governing emergence and persistence of
  antibiotic resistance in calf production are
  numerous and complex.
• The pressure of antibiotic use increases
  multi-resistant calf fecal E. coli.
• The role of other calf management factors on
  emergence of antibiotic resistance had not yet
  been characterized.

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Pre-weaned Calves

• Most antibiotic use in dairy is in pre-weaned
  calves and in fresh cows

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Development of Resistance

• Selection Pressure
• natural selection in bacteria
• Mutation
• spontaneous but then selected for
• Genetic Transfer
• conjugation
• transformation
• transduction

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Conjugation (a.k.a. bacterial sex)
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What Selection Pressures Exist in a Calf Raising
Area?
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Common Hutch-Calf Diseases

• Diarrhea
• Dietary
• E. coli, Salmonella enterica, Rota/Corona,
  Cryptosporidia,
• Respiratory disease- viruses, Pasteurella,
  Mannheimia, Salmonella septicemia and Mycoplasma
  spp,
• Ear infections (Otitis) Mycoplasma, Mannheimia
  and Pasteurella
• Septicemia, enteric/umbilical- Salmonella and E.
  coli
• Joint infections septicemia, injuries,
  Mycoplasma, etc.
• Umbilical infections E. coli, Arcanobacter

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Therapeutic Drugs Used by Calf Ranches

• Ceftiofur, Sulfa-trimethoprim, Tylosin,
  Tetracycline, Spectinomycin, Penicillin,
  Florfenicol, Tilmicosin, Gentamicin, Lincomycin,
  Enrofloxacin,
• Bismuth salts, Kaolin-Pectin, Charcoal
• Flunixin meglumine (Banamine), aspirin,
• Electrolytes

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Antibiotics in Milk

• Milk- Oxytetracycline
• .05-.1 mg/lb/feeding growth promoting
• 10 mg/lb/feeding treatment of E. coli diarrhea
  and Pasteurella pnemonia (7-14d)
• Neomycin- 10 mg neomycin sulfate/lb/day
• Coccidiostats
• Sulfisoxazole/Trimethoprim

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Immune Status of Calves
A large number of calves on dairies and calf
ranches may not have received enough colostrum.
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Inadequate or Failure Of Passive Transfer
37 heifers 62 bulls
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Determine Factors for Antibiotic Resistance in
Fecal E. coli From Pre-weaned Calves

• Sentinel organism- commensal E. coli
• Pathogenic bacteria- Salmonella
• Disk diffusion method- Kirby Bauer
• Resistance patterns - using cluster analysis

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Multi-drug Resistant Salmonella
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Cluster Analysis

• A statistical method of grouping isolates with
  similar resistance patterns
• Based upon the individual zones sizes to the
  antibiotics tested

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Factors Associated With Increasing Levels of
Resistance in Fecal E. coli From Pre-weaned
Calves (33 Farms in California)

• geographical location
• farm type (calf ranch, dairy, cow-calf)
• biosecurity measures (movement of animals)
• calf housing system
• calf-age
• calf diet
• antibiotic therapy type, intensity, individual
  calf data
• antibiotic prophylaxis
• coccidiostat use
• hygienic measures
• cow treatments farm level
• calving routines

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ResultsRisk Factors for Resistance

• AGE Risk for increasing levels of antibiotic
  resistance was highest for calves 3-14 days
  compared to newborns
• Risk decreased with age
• FARM TYPE Dairy and calf-ranch calves had more
  isolates with higher levels of resistance than
  cow-calf calves

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ResultsRisk Factors for Resistance

• TREATMENT For each additional Antibiotic
  treatment within 6 weeks, the risk of more
  multi-drug antibiotic resistance increased by 30
• Calves treated within 5 days of sampling had 5
  times higher risk for higher levels of resistance
  (multi-drug)

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Risk Factors for Multi-drug Resistance

• CLEANING Scraping or mechanically cleaning
  hutches between calves REDUCED levels of
  antibiotic resistance by 50
• Scraping manure from under the hutches weekly
  REDUCED the levels of antibiotic resistance by 70

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Salmonella in Pre-weaned Calves

• From 33 farms
• Isolated Salmonella
• 3686 fecal samples
• 278 (7.5) samples Salmonella-positive
• 55 of farms Salmonella-positive
• S. montevideo 38

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Antibiotic Resistance in Salmonella
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Results ConclusionsRisk Factors for Calf
Salmonella

• Fewer calves shed Salmonlella as they get older
• Shedding lowest in closed herd dairies
• Calves given antibiotics in milk replacer less
  likely to shed
• Calves getting supplemental antibiotics the first
  day of life more likely to shed Salmonella
  (ceftiofur, penicillin, gentamicin)

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What Happens When We Reduce Our Use of
Antibiotics?
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Objectives

• Determine if we can influence development and
  persistence of antibiotic resistance in commensal
  E coli
• Assess whether calf health and performance could
  be maintained without the use of antibiotics

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Group 1 Non-antibiotic biosecurity group
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Groups 2-4 On-ranch cohorts
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Drugs for Treatment and Prevention

• Group 4 Tetracycline HCl and neomycin sulfate in
  milk-replacer
• Group 3- 4 Ceftiofur for diarrhea and
  respiratory disease, Tilmicosin, Penicillin
• Group 1- 4 Bismuth salts, Kaolin-Pectin,
  Flunixin meglumine, Electrolytes, charcoal,
  probiotics

Extralabel use
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E. coli Susceptibility Testing

• Calves Sampled day of arrival, at 2 weeks, and 4
  weeks of age
• Each fecal sample was tested for antibiotic
  susceptibility to 12 antibiotics
• Isolates were grouped according to similar
  resistance patterns using cluster analysis

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Antibiotic Resistance Cluster Distribution
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ResultsRisks for Antibiotic Resistance

• For calves in Group 3, (no milk antibiotics)
  those getting treated with antibiotics had 3
  times higher risk for higher level of antibiotic
  resistance (multi-drug)
• However, the resistance does not persist for
  long-term
• In Group 4 Multi-drug resistance persisted up
  to the end of the trial

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Morbidity and Mortality

• Morbidity (sickness) days in trial without
  treatment, days to first treatment
• Mortality (death)
• days to death

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Odds for MORTALITY in Calves Getting Antibiotics
in the Milk Replacer and/or as Therapy
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Odds of Belonging to a Lower HEALTH CATEGORY
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Odds for DAYS TO FIRST TREATMENT
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Conclusions

• Failure of Passive Transfer is the most
  significant factor associated with morbidity and
  mortality
• Antibiotics in feed (Milk replacer) may be
  protective for calves lt 1 week of age but not
  apparently effective later on
• Therapeutic antibiotics are protective for calf
  morbidity and mortality

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Overall Conclusions

• Without antibiotics for treatment and prevention,
  it is difficult and labor-intensive to raise
  pre-weaned calves with inadequate or no colostrum
• Need to address problems of colostrum-deprived
  calves, high pathogen load, and environmental
  stress factors to successfully raise calves and
  minimize antibiotic use

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A Field Trial Evaluating Colostrum
Supplementation and Enhanced Nutrition in Calf
Milk Replacer for First 2 Weeks of Life
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3 Trials x 90 Calves in 3 Treatment Groups

• COLOSTRUM group - 10 gr IgG (70 grams Calves
  Choice Total Bronze-CCT in 1 cup) in their milk
  replacer fed twice daily for 14 days.
• CONTROL group - a placebo treatment with
  equivalent nutritional composition to the CCTG (1
  Cup), no IgG.
• MONITOR group - no supplements in the milk
  replacer.

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Odds of Diarrhea in a Calf
The table shows the likelihood that a calf on any
single day will have diarrhea compared to
reference.
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Days to Diarrhea Stratified on FPT
Proportion of calves
Failure PT Partial Failure PT Adequate PT
Days to diarrhea
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Days to Diarrhea by Treatment Group
Proportion of calves
Placebo Control Colostrum
Days to diarrhea
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Survival of Calves by FPT
Proportion of calves
Failure PT Partial Failure PT Adequate PT
Days
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Average Daily Weight Gain
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ADG in kg at 28 Days
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ADG in kg at Weaning (60 days)
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Take Home Message
Colostrum supplementation post-closure of the gut
will decrease diarrheal disease on calf ranches
and inlfuences weight gain in the first four
weeks of life.
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Antibiotic Resistance in Fecal Commensal E. coli
and Salmonella
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Antimicrobial Resistance of Fecal E. coli in
Calves at Day 1, 14 and 28 (sampling).
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Antibiotic Resistance Patterns of Fecal E. coli
in 3 Treatment Groups
Blue Placebo Control Green Monitor Red
Colostrum Suppl
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Alternatives to Antibiotics?

• Current calf-rearing systems
• Difficult to raise colostrum-deficient calves
  without any antibiotics
• In-feed antibiotics leads to sustained multi-drug
  resistance (up to 60 days) but also maintains
  health of calves
• Early Supplements help improve health of calves
• Management is the key?

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Targeted Therapy Trial

• Can using a protocol to identify and treat sick
  hutch calves reduce antibiotic use?

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Check Calves Daily
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Targeted Therapy groups
Conventional Treatment
Days to first Treatment
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Conclusions

• Calf groups receiving conventional antibiotic
  treatment had twice as much diarrhea as those
  receiving targeted treatment.
• Calves receiving antibiotics in milk for 14 days
  had 1.3 times more diarrhea as calves not
  receiving antibiotics in the milk.
• Direct medication cost for conventional therapy
  with antibiotics in the milk was 16.50 per calf,
  whereas targeted therapy with no antibiotics in
  the milk was 1.50.
• Calves receiving targeted therapy consumed more
  grain than calves receiving conventional therapy.

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What Can You Tell Your Clients?

• The keys to determine if calves need treatment is
  their attitude and milk consumption. All calves
  that are slow to drink, or do not finish their
  milk should be checked for fever and treated
  appropriately.
• Indiscriminate use of antibiotics does not
  improve the health of neonatal calves and may
  cost more and result in more days of diarrhea.

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Final Words

• Colostrum Management
• Colostrum Supplement
• Cleaning Hutches
• Targeted Therapy