Importance of Cephalosporins in Veterinary
Medicine,
with a focus on cattle production systems

Veterinary Medical Advisory Committee
Public Hearing, 25 September 2006

Kelly Lechtenberg, DVM, Ph.D.
Midwest Veterinary Services, Inc.
Oakland, Nebraska
 

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Table of Contents

• US cattle production systems
• Feedlot disease conditions
• Bovine Respiratory Disease (BRD)
• Disease management of BRD
• Cephalosporins in veterinary medicine
• Use of cephalosporins for BRD
• Conclusions 

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See Image on right

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US cattle production systems
Integration Diversity of Beef Production Systems

• Segmented Industry Structure
• High equity business in all sectors
• Traditional profit opportunities between sectors
• First input (calves) is geographically, genetically and immunologically diverse
• Significant consolidation is unlikely

• Net result on cattle
• Commingling is nearly assured
• Pathogen exposure is assured

• Infectious Disease will remain one of our major challenges

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US cattle production systems:
Integration in the Meat Industry – Structural Comparison

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US cattle production systems:
Midwest Feedlot Data (1988-2004) 
- Morbidity/ Mortality (% of Inventory) 

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US cattle production systems:
BRD = Most Common Cause of Morbidity
Antimicrobials reduce illness and death rate 

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US cattle production systems:
Infectious Pododermatitis (Musculoskeletal)  

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US cattle production systems:
Infectious Metabolic Disease Condition (Digestive)

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Bovine Respiratory Disease (BRD):
MF Data (1988-2004)
- Morbidity by Month (%)

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BRD “By the Numbers”
Economic Aspects 

• $ 71.2 Billion
• US consumer spending for beef was 71.2 billion. (Cattle-Fax, January 2006)

• > $1Billion
• Esimates indicate BRD costs more than $1 billion annually in the US. (Beef, January 2006)

• $ 13.90/head loss
• Lost perfomance and treatment costs
• Does not include labor and associated handling costs.
• Results in $400M loss on 29 million feedlot cattle each year. (Snowder et al., 2006, J. Anim. Sci, 84: 1999-2008)

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Bovine Respiratory Disease (BRD):
Infectious Etiology

• Major Viral Pathogens
  - IBR, BVD1, BVD2, BRSV, PI3
• Major Bacteria Pathogens
  - Mannheimia hemolytica
  - Pasteurella multocida
  - Histophilus somni
•  Stress + Pathogens = Disease
   

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Clinical Signs of BRD:
Depression, Dyspnea, Weakness

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Disease Management of BRD: 

• Therapeutic Efficacy is a function of:
  - Early Detection
  - Early Access
  - Early Therapy
  - Effective Antimicrobial Therapy
  - Successful Therapeutic Support (management)

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Disease Management of BRD:
Historic Background of Antibiotics Used for
Treatment of BRD in Cattle (FDA approved) 

• Older injectables (>10 years on market for treatment of cattle)
• ß-lactams (penicillin G, ampicillin, amoxicillin, *ceftiofur sodium)
• Sulfonamides (sulfadimethoxine)
• Tetracyclines (oxytetracycline)
• Macrolides (erythromycin, tylosin, tilmicosin)

*third generation cephalosporin

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Disease Management of BRD:
Historic Background of Antibiotics Used for
Treatment of BRD in Cattle (FDA approved)

• Newer injectables (<10 years on market)
• ß-lactams (*ceftiofur hydrochloride; *ceftiofur crystalline free acid)
• Fluoroquinolones (enrofloxacin; danofloxacin)
• Phenicols (florfenicol)
• Aminocyclitols (spectinomycin)
• Macrolides (tulathromycin)

*third generation cephalosporin
 

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Disease Management of BRD:
Some Factors Affecting Product Selection

• Response rate data
• Product attributes, e.g.
  - Safety
  - Spectrum
  - Route of administration
  - Dose volume
  - Ease of administration
  - Withdrawal period
• Availability of products  

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Disease Management of BRD:
Factors Affecting Therapeutic Response

• Age/Quality of cattle
• Shipping Stress
• Pathogens
• Processing Program
• Nutrition
• Immune status
• Stage of disease
• Early diagnosis
• Crew experience
• Therapeutic regimen
   

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Disease Management of BRD:
Assessment of Therapeutic Response

• Fever reduction, attitude, feed consumption, hydration status
• Mortality
• Retreats, repulls
• Treatment days
• Treatment cost
   

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Disease Management of BRD:
Treatment Success 

• Response rates in the same yard using the same treatments range from 55% to 86% to first treatment.
• Differences were not due to antibiotic failure, but calves in lower response group were lower priced, and took longer to assemble.

(R.A. Smith, Bovine Respiratory Disease, Sourcebook for the Veterinary Professional, 1996)

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Disease Management of BRD:
Treatment Success 

• Cattle that die BRD within 4 days of being pulled are likely late pulls.
• Calves treated for BRD within 5 days of shipping have a higher incidence of relapses and mortality compared to cases occurring later
• Case fatality are typically 6-8%

(R.A. Smith, Bovine Respiratory Disease, Sourcebook for the Veterinary Professional, 1996)

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Cephalosporins in veterinary medicine
(FDA approved) 

• 1st generation cephalosporins (1-GC)
• Cefadroxil (oral; dogs & cats)
• Cephapirin sodium/ benzathine (i.m.m.; dairy cows)

• 3rd generation cephalosporins (3-GC)
• Cefpodoxime (oral, dogs)
• *Ceftiofur sodium/ hydrochloride/ crystalline free acid (multiple applications)

*only FDA approved cephalosporin with BRD claim

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Use of cephalosporins for BRD:
NAHMS Feedlot Data

• NAHMS (National Animal Health Monitoring System)
• 1999 study on cattle feeding industry
• 12 major cattle feeding states participating (520 feedlots; 84.9% of U feedlots; 96.1% of US feedlot inventory)
• Report by USDA – APHIS - Veterinary Services
• Respiratory Disease Complex (BRD) most common cause of illness in cattle (small and large feedlots)
• 29 million feedlot cattle per year  
  

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Use of cephalosporins for BRD:
NAHMS Feedlot Data

• Use of antibiotics to prevent and treat BRD (Bovine Respiratory Disease)
• Metaphylaxis*
• 41.7 % of feedlots
• 10.4 % of cattle treated metaphylactically

• Therapeutic treatment
• 100 % of feedlots
• 14.4 % of cattle developed BRD after arrival (and were treated)
  

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Use of cephalosporins for BRD:
NAHMS Feedlot Data  

• Use of cephalosporins to prevent and treat BRD 
• Metaphylaxis
• 8.1 % of feedlots using metaphylaxis
• 5.4 % of cattle treated metaphylactically

• Therapeutic treatme
• 8.1 % of feedlots
• Primary antimicrobial in 6 % of feedlots
• For retreats in 8.5 % of feedlots
• For repulls in 11.7 % of feedlots

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Use of cephalosporins for BRD:
NAHMS Dairy Data: Weaned Heifers

• NAHMS (National Animal Health Monitoring System)
• 2002 study on dairy cattle industry
• 21 major dairy states participating (1,013 dairy operations; 83% of US dairy operations; 85.7% of US dairy cows
• Report by USDA - APHIS - Veterinary Services
• BRD most reported disease in dairy operations
• 3.8 million heifers as dairy cow replacements
   
    

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Use of cephalosporins for BRD:
NAHMS Dairy Data: Weaned Heifers

• Use of antibiotics to treat BRD (Bovine Respiratory Disease)
• Therapeutic treatment
• 95.4 % of dairy operations
• 4.7 % of weaned heifers were affected by BRD (97.5 % treated)
   

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Use of cephalosporins for BRD:
NAHMS Dairy Data: Weaned Heifers  

• Use of cephalosporins to treat BRD 
  - Therapeutic treatment
     - Primary antimicrobial in 4.6 % of dairy operations
     - Primarily used in 5.6 % of weaned heifers
  

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Use of cephalosporins for BRD:
Safety Aspects Recommending Cephalosporins for Use in
Treatment of BRD

• Animal safety: Proven safe
• Human safety: Proven safe
• User safety: Very safe treatment option 

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Use of cephalosporins for BRD:
(FDA approved, 3-GC, BRD) 

• Naxcel® (ceftiofur sodium),
   and
   Excenel® RTU (ceftiofur hydrochloride)
  - parenteral, multiple dose
  - CATTLE – treatment of bovine respiratory disease (shipping fever, pneumonia) associated with Mannheimia haemolytica, Pasteurella multocida, and Haemophilus somni; also for acute bovine interdigital necrobacillosis (foot rot, pododermatitis) associated with Fusobacterium necrophorum and Bacteroides melaninogenicus.
  - Once daily for a total of 3 – 5 consecutive days; 0.5 - 1.0 mg/ pound BW; pre-slaughter withdrawal of 4 days (Naxcel®) or 3 days (Excenel® RTU); no milk discard time

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Use of cephalosporins for BRD:
(FDA approved, 3-GC, BRD)

• Excede® (ceftiofur crystalline free acid)
  - parenteral, single dose
  - CATTLE – treatment of bovine respiratory disease (BRD, shipiping fever, pneumonia) associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni; also for control of respiratory disease in cattle which are at high risk of developing BRD associated with M. haemolytica, P. multocida, and H. somni (Haemophilus somnus).
  - One injection; 3.0 mg/ pound BW; 13-day pre-slaughter withdrawal; no milk discard period; not for veal calves
   

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Conclusions

• BRD remains a major health threat to cattle.
• BRD is of great economic importance to the US cattle production system.
• Early diagnosis and effective treatment of BRD is critical to achieve a positive clinical outcome.

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Conclusions

• The US beef industry needs access to safe and effective antimicrobial therapy for animals under its collective care.
• Safeguards are in place to provide for and document the use of antimicrobials that is:
  - Safe for users
  - Safe for animals
  - Safe for consumers of beef
  

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Conclusions 

• Cephalosporins have a proven safety record in veterinary medicine.
• Cephalosporins have a significant share among treatment options for BRD in cattle.
• A competitive range of approved cephalosporin class products will allow veterinarians more options to
  - Decide on specific treatment regimens
  - Help ensure continued availability of this class of compounds