# Presentation: 065880

## Importance of Macrolides in Veterinary Medicine

- Mike Apley, DVM, PhD
- Diplomate, American College of Veterinary Clinical Pharmacology
- Veterinary Diagnostic and Production Animal Medicine
- Iowa State University

## Macrolides in Veterinary Medicine

- 14 member ring
- erythromycin
- 16 member ring
- tylosin, tilmicosin

## Macrolide Susceptibility Testing

- The macrolide breakpoints reported here are adapted from the NCCLS M31-A2 document.
- The extended range information reflects extended dilutions used by some diagnostic laboratories utilizing microwell dilution systems.
- Of the macrolides, only tilmicosin has NCCLS validated breakpoints for veterinary applications.

## NCCLS macrolide breakpoints

| Drug | Susceptible  
 ( g/ml) | Intermediate
(g/ml) | Resistant  
 (≥g/ml) | Extended
Range
(g/ml) |
| --- | --- | --- | --- | --- |
| Erythromycin 
(Adapted from human) |  |  |  | 0.25 - 4 |
| 	Organisms other than streptococci | 0.5 | 1 - 4 | 8 |  |
| 	Streptococci | 0.25 | 0.5 | 1 |  |
| Tilmicosin (Veterinary derived) |  |  |  | 4 – 32 |
| 	Cattle (BRD) P. hemolytica | 8 | 16 | 32 |  |
| 	Swine respiratory disease Actinobacillus pleuropneumoniae,  Pasteurella multocida | 16 |  | 32 |  |

## Label Applications

- Label applications in this presentation are adapted from labels as presented in the Compendium of Veterinary Products (North American Compendiums).
- The listing of a label application does not indicate the frequency or extent of use in animals.

## Label Applications in Food Animals

- Tylosin
- Label Indications

## Tylosin Injectable solution

- In beef cattle and nonlactating dairy cattle:  indicated for use in the treatment of
- bovine respiratory complex (shipping fever, pneumonia) usually associated with *Pasteurella multocida* and *Actinomyces pyogenes*;
- foot rot (necrotic pododermatitis) and diphtheria caused by *Fusobacterium necrophorum*,
- and metritis caused by *Actinomyces pyogenes*.

## Tylosin Injectable solution

- In swine:  indicated for use in the treatment of
- swine arthritis caused by *Mycoplasma hyosynoviae*,
- swine pneumonia caused by *Pasteurella* spp.,
- swine erysipelas caused by *Erysipelothrix rhusiopathiae*,
- acute swine dysentery associated with *Brachyspira* (formerly *Serpulina** *or *Treponema*) *hyodysenteriae*  when followed by appropriate medication in the drinking water and/or feed.

## Tylosin Phosphate Feed Additive

-  Beef Cattle:
- For reduction of incidence of liver abscesses caused by *Fusobacterium necrophorum* and *Actinomyces pyogenes*.

## Tylosin Phosphate Feed Additive

- Swine:
- For increased rate of weight gain and improved feed efficiency,
- For prevention and/or control of porcine proliferative enteropathies (ileitis) associated with *Lawsonia intracellularis*,
- For prevention of swine dysentery (bloody scours) caused by *Serpulina hyodysenteriae*,

## Tylosin Phosphate Feed Additive

- Swine (cont.):
- For maintaining weight gains and feed efficiency in the presence of atrophic rhinitis,
- For treatment and control of swine dysentery (bloody scours) caused by *Serpulina hyodysenteriae* following initial medication with tylosin soluble in drinking water.

## Tylosin Phosphate Feed Additive

- Chickens: For increased rate of weight gain and improved feed efficiency.
- Laying Chickens: For improving feed efficiency.
- Broiler and Replacement Chickens: To aid in the control of chronic respiratory disease caused by *Mycoplasma gallisepticum*.

## Tylosin Tartrate Water Medication

- Swine:
- For the treatment and control of swine dysentery caused by *Serpulina hyodysenteriae* or other pathogens sensitive to tylosin

## Tylosin Tartrate Water Medication

- Chickens:
- As an aid in the treatment of chronic respiratory disease (CRD) caused by *Mycoplasma gallisepticum* sensitive to tylosin in broiler and replacement chickens.
- For the control of chronic respiratory disease (CRD) caused by *Mycoplasma gallisepticum* sensitive to tylosin at time of vaccination or other stress in chickens.
- For the control of chronic respiratory disease (CRD) caused by *Mycoplasma synoviae* sensitive to tylosin in broiler chickens.

## Tylosin Tartrate Water Medication

- Turkeys:
- For maintaining weight gains and feed efficiency in the presence of infectious sinusitis caused by Mycoplasma gallisepticum sensitive to tylosin.

## Tylosin Tartrate as part of cattle  ear implants

- One product line of cattle growth promoting ear implants is available containing a pellet of tylosin tartrate (29 mg) in addition to the hormone-containing pellets.

## Label Applications in Food Animals

- Tilmicosin
- Label Indications

## Tilmicosin Injectable Solution

- Cattle and Sheep... indicated for the treatment of bovine respiratory disease (BRD) and ovine respiratory disease (ORD) associated with *Mannheimia (Pasteurella) haemolytica*.
- Cattle ... indicated for the control of respiratory disease in cattle at high risk of developing BRD associated with *Mannheimia (Pasteurella) haemolytica*.

## Tilmicosin Feed Additive

- Swine:
- ... for the control of swine respiratory disease associated with *Actinobacillus pleuropneumoniae* and *Pasteurella multocida*.
- Animal feed bearing or containing this veterinary feed directive drug shall be fed to animals only by or upon a lawful veterinary feed directive issued by a licensed veterinarian in the course of the veterinarian's practice.

## Label Applications in Food Animals

- Erythromycin
- Label Indications

## Erythromycin Injectable Solution

- Beef Cattle:
- Shipping fever, pneumonia (or pneumonia-enteritis complex),
- foot rot,
- stress (handling, transporting to feedlot, vaccination, dehorning, etc.),
- metritis.

## Erythromycin Injectable Solution

- Dairy Cattle:
- Pneumonia,
- foot rot,
- metritis,
- shipping fever,
- stress (handling, transporting to and from pasture, etc.).

## Erythromycin Injectable Solution

- Swine (Hogs):
- pneumonia,
- rhinitis,
- bronchitis.
- Sows:
- metritis,
- leptospirosis (at farrowing time).
- Baby Pigs (one week of age or older):
-  “scours".

## Erythromycin Injectable Solution

- Sheep:
- Prevention of "dysentery"** in newborn lambs,
- upper respiratory infections.
-   ** Where organisms susceptible to erythromycin may be the infective agent.

## Erythromycin Mastitis Syringe

- A mastitis syringe for lactating cows that is effective against the leading mastitis-causing organisms: *Staphylococcus aureus*, *Streptococcus agalactiae*, *Streptococcus dysgalactiae*, and *Streptococcus uberis*...
- A mastitis syringe for nonlactating cows that is effective against the following major mastitis-causing organisms: *Staphylococcus aureus*, *Streptococcus agalactiae*, *Streptococcus nonagalactiae*

## Erythromycin Thiocyanate Feed Additive

- Chickens and Turkeys:
- As an aid in the prevention and reduction of lesions and in lowering severity of chronic respiratory disease.
- Chickens:
- As an aid in the prevention of infectious coryza.
- Chickens and Turkeys:
-  As an aid in the prevention of chronic respiratory disease during periods of stress.

## Erythromycin Phosphate        Water Medication Solution

- In Broilers and Replacement Chickens:
- As an aid in the control of Chronic Respiratory Disease due to *Mycoplasma gallisepticum* susceptible to erythromycin.
- In Replacement Chickens and Chicken Breeders:
- As an aid in the control of Infectious Coryza due to *Haemophilus gallinarum* susceptible to erythromycin.

## Erythromycin Phosphate        Water Medication Solution

- In Growing Turkeys:
- As an aid in the control of Bluecomb (Non-specific Infectious Enteritis) caused by organisms susceptible to erythromycin.

## Data Related to Use

- National Animal Health Monitoring Service
- 	_[http://www.aphis.usda.gov/vs/ceah/ncahs/nahms/index.htm](http://www.aphis.usda.gov/vs/ceah/ncahs/nahms/index.htm)_
- Beef – Feedlot, 1999
- Swine, 2000

## NAHMS Beef Feedlot Data

- Survey conducted in 12 states
- Approximately 84% of U.S. feedlot inventory
- The survey estimated that 14.4% of all cattle placed in feedlots developed “respiratory disease such as shipping fever” after arrival.

## NAHMS Beef Feedlot Data

- “Approximately 2/3 of the metaphylactically treated cattle in both large and small feedlots were administered tilmicosin.  These cattle represent 6.7% of cattle placed on feed.”

## NAHMS Beef Feedlot Data

- “Tilmicosin, florfenicol, and tetracyclines were the primary antimicrobial drugs for the initial treatment of bovine respiratory disease (BRD).”
- Tilmicosin 31.3%
- Florfenicol 21.9%
- Tetracyclines 21.6%

## NAHMS Beef Feedlot Data

- “Percent of feedlots that used the following antimicrobials in feed or water as a health or production management tool by antimicrobial used and by feedlot capacity.”
- Tylosin, 1000 – 7999 capacity, 12.1%
- Tylosin, 8000 or more capacity, 41.5%

## NAHMS Beef Feedlot Data

- “For all cattle placed in the specified feedlot size groups, percent of cattle that received each of the following antimicrobials in the feed or water as a health or production tool by feedlot capacity.”
- Tylosin, 1000 – 7999 capacity, 16.1%
- Tylosin, 8000 or more capacity, 47.2%
- Tylosin, all feedlots, 42.3%

## NAHMS Beef Feedlot Data

- For feedlots that used the specified antimicrobials in the feed or water as a health or production management tool, average number of days ... by arrival weight.
- Tylosin, less than 700 lbs, 145 days
- Tylosin, 700 lbs or greater, 138 days

## NAHMS Swine Data

- A 2000 – 2001 survey conducted in 17 states representing 94% of the U.S. pig inventory.

## NAHMS Swine Data

- For sites that had any grower/finisher pigs, percent of sites that gave the following antimicrobials in water to grower/finisher pigs in the previous 6 months by the primary reason for giving them.
- Tylosin, respiratory disease treatment, 1.2%
- Tylosin, enteric disease treatment, 2.7%
- Tylosin, any reason (includes above), 4.1%
- Duration in water (all reasons) averaged 4.9 days

## NAHMS Swine Data

- For sites that had any grower/finisher pigs, percent of sites that gave the following antimicrobials by injection to grower/finisher pigs in the previous 6 months by the primary reason for giving them.
- Tylosin, disease prevention, 3.5%
- Tylosin, respiratory disease treatment, 13.8%
- Tylosin, enteric disease treatment, 11.1%
- Tylosin, any reason (includes above), 30.7%

## NAHMS Swine Data

- For sites that had any grower/finisher pigs, percent of sites that gave the following antimicrobials in feed to grower/finisher pigs in the previous 6 months by the primary reason for giving them.
- Tylosin, growth promotion, 31.3%
- Tylosin, disease prevention, 13.2%%
- Tylosin, respiratory disease treatment, 1.4%
- Tylosin, enteric disease treatment, 10.3%
- Tylosin, any reason (includes above), 56.3%
- Average number of days in feed (all reasons), 62.3

## NAHMS Swine Data

- For sites with nursery-age pigs, percent of sites that used the following antimicrobials or feed additives in the feed of nursery age pigs....
- Tilmicosin, 3.6%, average days of 28.5
- Tylosin, 23.2%, average days of 26.7
- Tylosin/sulfamethazine, 6.6%, average days of 23.7

## Extralabel Uses of Macrolides

- Erythromycin oral use in **dogs and cats**
- Very limited use
- Significant gastrointestinal upset is possible
- Use of veterinary macrolides is not advisable in **non-ruminant herbivores (horses, rabbits)**
- Adverse effects related to enteric flora imbalance

## Macrolide Use in Foals

- Oral use in **foals** for *Rhodococcus equi** *respiratory infection.
- Resistance to erythromycin/rifampin combination is being encountered
- Erythromycin-related hyperthermia has been reported in foals.
- Recent work has characterized a combination of clarithromycin/rifampin as superior to azithromycin/rifampin and erythromycin/ rifampin for this application1
- 	1Gigure, et al. Retrospective comparison of azithromycin, clarithromycin, and erythromycin for the treatment of foals with Rhodococcus equi pneumonia.  J Vet Intern Med  18(4): 568-73, 2004