Evolution of Antibiotic Use and Veterinary Feed Directive Changes

Sonia Mumford DVM & Guppy Blair DVM Olympia Fish Health Center & Idaho Fish Health Center

History

Alfred Eisenstaedt/Time Life Pictures/Getty

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Ernest Chain Howard Florey

1945 – Nobel Peace Prize

http://www.nobelprize.org/nobel_prizes/medicine/laureates/1945/chain-bio.html

1928 – Alexander Fleming

Alexander Fleming:

“I hope this evil can be averted.”

“The thoughtless person playing with penicillin treatment is morally responsible for the death of a man who succumbs to the infection with the penicillin resistant organism”

And so begins the battle….

http://cooper.imb.uq.edu.au/community_background.html

http://www.mtaofnj.org

http://thelightmedia.com/posts/21787-top-10 -best-accidental-scientific-discoveries-and-inventions

From January to May 1943, only 400 million units of penicillin had been made; by the time the war ended, U.S. companies were making 650 billion units a month.

http://www.pbs.org/wgbh/aso/databank/entries/dm28pe.html

How did we do?

Mid1930s 1937 1938 1940 1943 1950’s

How are we doing now?

When did this chemical warfare begin?

Doctorbhatia.com

http://cooper.imb.uq.edu.au/community_background.html

How many soldiers in the battle?

Most abundant & diverse life form on earth 36 x 1028 species in sea-water alone (Discover Magazine 2007) Estimated:

#bacterial cells in a gram of soil

#bacterial cells in a milliliter of water

1 billion 1 million

We are not alone….

(with a wide variation) (Nature 2016)

Cell Type Aprox. # Cells Human Cells In Human Body 30 trillion Bacteria in and on Human Body 39 trillion

Use of Antibiotics: applying a selective pressure for resistance

en.wikipedia.org

From ANTIMICROBIAL PHARMACODYNAMICS: CRITICAL INTERACTIONS OF ‘BUG AND DRUG’ George Drusano Nature 2004

If bacteria come into contact with other bacteria, they can trade genetic information (DNA)

And it isn’t even a fair fight….

http://mrsa-research-center.bsd.uchicago.edu/images/Cartoon_antibioticresistance_joke.jpg

Surely we’re prepared….

The problem:

“The problem is so serious that it threatens the achievements of modern medicine. A post-antibiotic era—in which common infections and minor injuries can kill—is a very real possibility for the 21st century.”

Estimated 10 million fatalities globally.

What is causing the problem?

Exact mechanisms unknown… But….

47 million excess prescriptions annually…

157 million human medicine prescriptions…….. to patients that may not take the antibiotics as directed…

An estimated* 70% (by weight) of antibiotics sold in 2011 was for use in animals

*not all antibiotics sold are actually used

How about world aquaculture use of antibiotics?

Chile is the second largest producer of farmed salmon and the only important developing country producer--300 tons of antibiotics per year

The largest salmon producer, Norway, uses less than 1 ton per year(relying instead on vaccination and husbandry measures to control diseases).

http://www.fao.org/antimicrobial-resistance/background/what-is-it/en/

Antibiotic use in US Aquaculture?

No solid numbers……

We don’t know exact mechanisms or what group(s) to blame…

But we know it’s complicated…

Dissemination of antibiotics and antibiotic resistance within agriculture, community, hospital, wastewater treatment, and associated environments.

Julian Davies, and Dorothy Davies Microbiol. Mol. Biol. Rev. 2010;74:417-433

How much of these antibiotics are used in our hatcheries?

My guess….

But, we should do our part of antibiotic stewardship….

Most hatchery fish fall under “Food Animals”

FDA changing how medically important antibiotics can legally be used in feed/water for food-producing animals. Eliminate use for production purposes Bring remaining therapeutic uses under the supervision of

a veterinarian

And we must comply with the new regulations

Veterinary Feed Directive(VFD) Rule

Veterinarians must be licensed in the state the VFD is issued*

Requires a Valid Client Patient Relationship (VCPR) (varies state to state)

Veterinarian requirements: Sufficient knowledge of the patient(s) Assume responsibility of diagnosis, treatment Provide follow up

Client requirements: Agrees to follow veterinarian’s instructions.

*Some specific exceptions

Recommendations for timely & smooth VFDs

Especially for hatcheries medicated feed/ immersion (marking) are anticipated, PRIOR to the need: Work with a veterinarian to establish a Valid Client

Patient Relationship (VCPR) with hatchery Confirm that you have a source for medicated

feed/immersion (must be authorized distributor)

How the process could work once a VCPR is established:

2 yrs

Optional Information

No refills. A treatment using a VFD

must be completed prior to the expiration date set by the veterinarian.

Must display prominently on feed bag:

More on VFDs

Which fish drugs need a VFD?

Generic Name Examples of Brand Name Florfenicol Aquaflor® Oxytetracycline Terramycin® 200, Pennox® 343,

Terramycin® 343 Sulfadimethoxine & Ormetoprim Romet 30, Romet TC

Can you legally Extra-label a VFD?

NO. But, under a specific set of circumstances, for minor species, FDA use “enforcement discretion” and may not prosecute. Veterinarian takes on the liability and responsibility for additional documentation and requirements.

What is a minor species?

What isn’t a VFD drug?

Investigational New Animal Drugs (INADs)

Treatments used to kill microorganisms that are not medically important for Humans:

(ie: Chloramine T, Formalin, Hydrogen Peroxide)

What additional FDA measures will be taken? Working to change label for remaining antimicrobial

drugs with no limit on duration for administration to a food animal

Proposed rule: Drug sponsors include species specific information in reporting requirements to FDA

Working to obtain more information on indication, dose, and duration of antibiotics given by species

One last thing…Not VFD….

Remember, a veterinarian must have a valid VCPR to write extralabel prescriptions. If using an approved drug, know the labelled use(s). ANY deviation from label (ie dose, duration, indication, species etc.) requires a prescription.

Drug Indication Deviation from Label Formalin Ich Longer duration Formalin Fungal Infection Treatment of fish, not eggs

QUESTIONS???