# Presentation: 545582

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

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

**Veterinary Medical Advisory Committee**
**Public Hearing, 25 September 2006**

## 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**

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

**Kelly Lechtenberg...**
**DRAFT (1.6) 25 August 2006 **

## 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**_

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

**SEED STOCK**

**COW / CALF**

**STOCKER**

**FEEDLOT**

**PACKER**

**I**
**N**
**T**
**E**
**G**
**R**
**A**
**T**
**O**
**R**

**SEED STOCK**

**FARROW**
**to**
**FINISH**

**PACKER /**
**PROCESSOR**

**I**
**N**
**T**
**E**
**G**
**R**
**A**
**T**
**O**
**R**

**BEEF**

**PORK**

**POULTRY**

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

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

## US cattle production systems:

**BRD = Most Common Cause of Morbidity**
**Antimicrobials reduce illness and death rate**

## US cattle production systems: Infectious Pododermatitis (Musculoskeletal) 

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

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

## 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)

## 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**

## Clinical Signs of BRD:

**Clinical Signs of BRD:**
** ****Depression, Dyspnea, Weakness**

## Disease Management of BRD:

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

## 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

## 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

## 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**

## 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**

## Disease Management of BRD: Assessment of Therapeutic Response

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

## 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)

## 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)

## 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 **

## 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 US 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**

## 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)**
*******antimicrobial treatment of cattle at high risk to develop BRD **

## 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 treatment**
**8.1 % of feedlots **
**Primary antimicrobial in 6 % of feedlots **
**For retreats in 8.5 % of feedlots **
**For repulls in 11.7 % of feedlots**

## 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**

## 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)**

## 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**

## 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**

## 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**

## 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**

## 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 positve clinical outcome.**

## 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**

## 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**