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Better Milk Quality from
Better Mastitis Therapy Decisions




   Dr. Ron Erskine, Michigan State University
Mammitis:
      Inflammation of the Bag
Treatment : Prevention
  •Bichloride of Mercury, 2 grains
  •Boracic Acid, 2 drams
  •q.s. One quart water,
    intramammary infusion


              CJ Korinek, The Veterinarian, 1915
XXX
Alternative Therapies
Tanker loads with antibiotic residues have
decreased ………




• Has the amount of drug use changed ?

• Has the amount of Extra Label Drug Use
  changed?
Antimicrobial Drug Use




106 doses/week/1,000 cows       100 doses/week/1,000 cows
Adult cows                      All animals
Survey                          Trash Collection

Pol and Ruegg, JDS, 90:2007     Saini et al, JDS, 95:1209, 2012
Extra Label Drug Use- IMM administration
 20 Wisconsin dairy herds

• 11 Herds
    Ampicillin -   6 herds
    Ceftiofur -    3 herds
    Gentamicin- 3 herds
    Penicillin- 1 herd
    Miconazole- 1 herd
    Tetracycline- 1 herd
    Veterinary Magic Bullets- 2 herds
    Sulfamethoxazole/Trimethoprim – 2 herds
                             Pol and Ruegg JDS 90: 2007
Implications for failure of therapy

• “Drugs just don’t work the way they use
  to……”
  • Antimicrobial resistance ?
  • Limited drugs for use in dairy cattle ?
  • Immune stress ?
  • Higher milk production?
Is AMR in mastitis pathogens emerging?




• ‘scientific evidence does not support a
  widespread, emerging resistance among
  mastitis pathogens to antibacterial drugs’
AMR in mastitis pathogens emerging ?



• Staph aureus

• 50 to 60% of S aureus isolates resistant to
  unprotected β-lactam drugs
  • Numerous studies
  • Forty years
  • No evidence of any change
Is antibacterial resistance in mastitis
 pathogens emerging?
 Temporal studies: same laboratory
              S aureus    Strep   E. coli        Coagulase
                                                 negative
                                                 staph
Mackie, et    N/C         ----    N/C            ----
al. 1989                          (coliforms)
Erskine, et   N/C         N/C     N/C            ----
al. 2002
Makovec       Erythromycin N/C    Erythromycin   Lincomycin
and Ruegg,    Lincomycin                         Pirlimycin
2003
US National Residue Program -2010
• Kidney Inhibition Swab test or Fast Antimicrobial
  Screen Test
• 211,733 Inspector Generated Samples
  • 7,000 positive samples
  • 2,043 confirmed violative residues (1,609 animals)




              2012 Residue Sampling Plans, USDA FSIS
2010 Inspector-generated Violations
900
                                Beef cows
800
                                Bob veal
700
                                Bulls
600                             Dairy cows
500                             Formula fed veal
400                             Goat
300                             Heavy calves
200                             Heifers

100                             Market hogs
                                Non-formula fed veal
 0
                                Steers
FDA Survey

• The long-anticipated drug-residue-sampling
  survey by the U.S. Food and Drug Administration
  has begun.
• 900 milk samples from dairy farms had a cull
  dairy cow residue violation
• 900 milk samples from dairies at large.
• 26 different drugs
                      Dairy Herd Network, Jan 10, 2012
FDA Bulk Tank Sampling Program
Mastitis……..

• Largest cause of
  antimicrobial drug
  use in dairy cows
Antibiotics 101

 Concentration-dependent inhibition
 Magnitude above MIC enhances killing
  • Peak serum > 10 times MIC


 Time-dependent inhibition
 Time above MIC, not peak concentration

     • All labeled drugs for use in lactating
       dairy cattle
Antibiotics 101

Dose intervals-
  • Holstein calves treated with chloramphenicol 4x
    more likely to die if treated once per day as
    opposed to twice per day (Waltner-Toews, Can Vet J, 1986)
Duration
  • 2 days after clinical and microbiological
    resolution, severe cases: 7-10 days, chronic: may
    involve months (Giguere, et al. Antimicrobial Therapy in
    Veterinary Medicine, 4th edition, 2006, pg 113)
Ampicillin Trihydrate (Polyflex)
  “3 days treatment is usually adequate, but
  treatment should be continued for 48 to 72 hours
  after the animal has become afebrile (up to 7
  days)”
Extended mastitis therapy :
subclinical mastitis
 • 125 mg ceftiofur cure rates
    • 10 % : control
    • 39 % : 2 days
    • 54 % : 5 days
    • 66 % : 8 days
       • Staph aureus 36%
       • Strep uberis 67%
       • Strep dysgalactiae 80 %
       • CNS 86 %
                                   (Oliver, et al, JDS, 2004)
Is extended therapy right for you?
Depends on the herd
Concentration Milk:
                    Drug                               Plasma
Ceftiofur                                               <1%
Sulfadimethoxine                                        18%
Penicillin                                              19%
Ampicillin                                              27%
Spectinomycin                                           75%
Tetracycline                                           140%
Tylosin                                                250%
Lincomycin                                             450%
Erythromycin                                           650%

Adapted from Langston, Antimicrobial Use in Food Animals, in Howard &
Smith ed., Current Veterinary Therapy food animal practice, IV.
Making Better Therapeutic Choices

• Repeat Offenders
  • Duration of infection
  • Lactation
  • Higher SCC
  • Multiple infected quarters
• Non-responsive pathogens
  • Mycotic organisms
    (Candida), Prototheca, Pseudomonas, Mycoplasma,
     Serratia, Nocardia, Proteus, Pasteurella, etc.
S. Nickerson
MILD CLINICAL MASTITIS




                          Culture
CHRONIC ???


                                                   Gram
    Yeast, Pseudomonas, etc       Coliforms       Positive
      No organism isolated

                                        ????

                              Administer IMM antibiotics
No antibiotic
treatment                     Records
Culture based therapy

• 3,500 cow dairy - MI (Hess et al, 2003)
   • Reduced days withheld by 80%
   • Two full time veterinarians
   • Laboratory
• 4 herd study - SD and MI (Wagner, et al, 2007)
   • Bacteriology skills highly variable among herds
• 8 herd study - MN, WI, ON ( Lago et el, JDS, 2011)
   • Reduced antibiotic use 50%
Culture Based Therapy
 Effects on lactation

                      Immediate Therapy    Culture Based
Bacteriologic cure*   71 %                 60%
Milk discard days*    5.9                  5.2
Herd removal          28%                  32%
Days at removal       160                  137
Relapse of clinical   35 %                 43 %
mastitis
Days at relapse       78                   82
LSCC                  4.2                  4.4

       * 21 days
                                          Lago, et al JDS, 2011
SEVERE CLINICAL
                                   MASTITIS



Fluids
Anti-Inflammatory
                                      Culture
IMM and Systemic antibiotics




Coliforms                                                Gram Positive
Continue antibiotics                                     Continue IMM antibiotics
Supportive care


                       Unusual Pathogens (e.g.,
                       Pseudomonas, Prototheca)
                       No antibiotics, Supportive care
It’s not the drugs…….
it’s how we use them!

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Better Milk Quality from Better Mastitis Therapy Decisions- Dr. Ron Erskine

  • 1. Better Milk Quality from Better Mastitis Therapy Decisions Dr. Ron Erskine, Michigan State University
  • 2. Mammitis: Inflammation of the Bag Treatment : Prevention •Bichloride of Mercury, 2 grains •Boracic Acid, 2 drams •q.s. One quart water, intramammary infusion CJ Korinek, The Veterinarian, 1915
  • 3.
  • 5. Tanker loads with antibiotic residues have decreased ……… • Has the amount of drug use changed ? • Has the amount of Extra Label Drug Use changed?
  • 6. Antimicrobial Drug Use 106 doses/week/1,000 cows 100 doses/week/1,000 cows Adult cows All animals Survey Trash Collection Pol and Ruegg, JDS, 90:2007 Saini et al, JDS, 95:1209, 2012
  • 7. Extra Label Drug Use- IMM administration 20 Wisconsin dairy herds • 11 Herds  Ampicillin - 6 herds  Ceftiofur - 3 herds  Gentamicin- 3 herds  Penicillin- 1 herd  Miconazole- 1 herd  Tetracycline- 1 herd  Veterinary Magic Bullets- 2 herds  Sulfamethoxazole/Trimethoprim – 2 herds Pol and Ruegg JDS 90: 2007
  • 8. Implications for failure of therapy • “Drugs just don’t work the way they use to……” • Antimicrobial resistance ? • Limited drugs for use in dairy cattle ? • Immune stress ? • Higher milk production?
  • 9. Is AMR in mastitis pathogens emerging? • ‘scientific evidence does not support a widespread, emerging resistance among mastitis pathogens to antibacterial drugs’
  • 10. AMR in mastitis pathogens emerging ? • Staph aureus • 50 to 60% of S aureus isolates resistant to unprotected β-lactam drugs • Numerous studies • Forty years • No evidence of any change
  • 11. Is antibacterial resistance in mastitis pathogens emerging? Temporal studies: same laboratory S aureus Strep E. coli Coagulase negative staph Mackie, et N/C ---- N/C ---- al. 1989 (coliforms) Erskine, et N/C N/C N/C ---- al. 2002 Makovec Erythromycin N/C Erythromycin Lincomycin and Ruegg, Lincomycin Pirlimycin 2003
  • 12. US National Residue Program -2010 • Kidney Inhibition Swab test or Fast Antimicrobial Screen Test • 211,733 Inspector Generated Samples • 7,000 positive samples • 2,043 confirmed violative residues (1,609 animals) 2012 Residue Sampling Plans, USDA FSIS
  • 13. 2010 Inspector-generated Violations 900 Beef cows 800 Bob veal 700 Bulls 600 Dairy cows 500 Formula fed veal 400 Goat 300 Heavy calves 200 Heifers 100 Market hogs Non-formula fed veal 0 Steers
  • 14. FDA Survey • The long-anticipated drug-residue-sampling survey by the U.S. Food and Drug Administration has begun. • 900 milk samples from dairy farms had a cull dairy cow residue violation • 900 milk samples from dairies at large. • 26 different drugs Dairy Herd Network, Jan 10, 2012
  • 15. FDA Bulk Tank Sampling Program
  • 16. Mastitis…….. • Largest cause of antimicrobial drug use in dairy cows
  • 17. Antibiotics 101  Concentration-dependent inhibition  Magnitude above MIC enhances killing • Peak serum > 10 times MIC  Time-dependent inhibition  Time above MIC, not peak concentration • All labeled drugs for use in lactating dairy cattle
  • 18. Antibiotics 101 Dose intervals- • Holstein calves treated with chloramphenicol 4x more likely to die if treated once per day as opposed to twice per day (Waltner-Toews, Can Vet J, 1986) Duration • 2 days after clinical and microbiological resolution, severe cases: 7-10 days, chronic: may involve months (Giguere, et al. Antimicrobial Therapy in Veterinary Medicine, 4th edition, 2006, pg 113)
  • 19. Ampicillin Trihydrate (Polyflex) “3 days treatment is usually adequate, but treatment should be continued for 48 to 72 hours after the animal has become afebrile (up to 7 days)”
  • 20. Extended mastitis therapy : subclinical mastitis • 125 mg ceftiofur cure rates • 10 % : control • 39 % : 2 days • 54 % : 5 days • 66 % : 8 days • Staph aureus 36% • Strep uberis 67% • Strep dysgalactiae 80 % • CNS 86 % (Oliver, et al, JDS, 2004)
  • 21. Is extended therapy right for you? Depends on the herd
  • 22.
  • 23. Concentration Milk: Drug Plasma Ceftiofur <1% Sulfadimethoxine 18% Penicillin 19% Ampicillin 27% Spectinomycin 75% Tetracycline 140% Tylosin 250% Lincomycin 450% Erythromycin 650% Adapted from Langston, Antimicrobial Use in Food Animals, in Howard & Smith ed., Current Veterinary Therapy food animal practice, IV.
  • 24. Making Better Therapeutic Choices • Repeat Offenders • Duration of infection • Lactation • Higher SCC • Multiple infected quarters • Non-responsive pathogens • Mycotic organisms (Candida), Prototheca, Pseudomonas, Mycoplasma, Serratia, Nocardia, Proteus, Pasteurella, etc.
  • 26. MILD CLINICAL MASTITIS Culture CHRONIC ??? Gram Yeast, Pseudomonas, etc Coliforms Positive No organism isolated ???? Administer IMM antibiotics No antibiotic treatment Records
  • 27. Culture based therapy • 3,500 cow dairy - MI (Hess et al, 2003) • Reduced days withheld by 80% • Two full time veterinarians • Laboratory • 4 herd study - SD and MI (Wagner, et al, 2007) • Bacteriology skills highly variable among herds • 8 herd study - MN, WI, ON ( Lago et el, JDS, 2011) • Reduced antibiotic use 50%
  • 28. Culture Based Therapy Effects on lactation Immediate Therapy Culture Based Bacteriologic cure* 71 % 60% Milk discard days* 5.9 5.2 Herd removal 28% 32% Days at removal 160 137 Relapse of clinical 35 % 43 % mastitis Days at relapse 78 82 LSCC 4.2 4.4 * 21 days Lago, et al JDS, 2011
  • 29. SEVERE CLINICAL MASTITIS Fluids Anti-Inflammatory Culture IMM and Systemic antibiotics Coliforms Gram Positive Continue antibiotics Continue IMM antibiotics Supportive care Unusual Pathogens (e.g., Pseudomonas, Prototheca) No antibiotics, Supportive care
  • 30. It’s not the drugs……. it’s how we use them!