Defining antibiotic stewardship in veterinary

and human medicine for the rest of this century

Michael D. Apley, DVM, PHD

Diplomate American College of Veterinary Clinical Pharmacology
Definitions
Antibiotic a substance produced by a living
organism (usually bacteria or fungi) that inhibits
the growth of other microorganisms, typically
bacteria.
Some targets are specifically named, such as
antifungals, antiprotozoals, anticoccidials.

Antimicrobial A broader category which includes

the antibiotics as well as compounds produced
synthetically
Sulfas
Fluoroquinolones (e.g., Cipro)
Disinfectants are examples of environmentally applied
antimicrobials
 Definitions
Resistance
Clinical resistance the inability of an
antimicrobial to make a difference in the
outcome of disease caused by an infectious
agent.
Defined through breakpoints which characterize the
potential for clinical effect by evaluating the
concentration of the antimicrobial necessary to inhibit
growth of the target organism in the laboratory.
Intrinsic this resistance is due to a characteristic of
the target organism which does not allow activity of
the antimicrobial, such as absence of the binding site.
Acquired the target organism was once susceptible,
and now has either developed (through mutation), or
received from another organism (acquired), a
mechanism to resist the effects of the antimicrobial.
 Definitions
Resistance
Epidemiological resistance - a change in
the distribution of a bacterial population
as characterized by the minimal inhibitory
concentrations of multiple isolates.
Definitions
Medically important
In the U.S., the medically important antibiotics are
defined in Appendix A of Guidance for Industry #152.
These are antibiotics defined as being important,
highly important, or critically important to human
health.

Non-medically important
These are antibiotic groups not listed in GFI
An example is the ionophores, which are not used in
human medicine and have no demonstrated or
reasonably hypothesized link to any antibiotic used in
human medicine.
WHO list
The World Health Organization has a
list of medically important
antimicrobials also. They highlight 5
as the most critically important
Cephalosporins
Fluoroquinolones
Macrolides
Glycopeptides
Carbapenems
Some antibiotic use
category definitions
Growth Promotion the use of an
antibiotic to increase efficiency in
the form of feed required per unit of
weight gain or the rate at which
weight is gained.
This category of use for medically
important antibiotics is no longer legal
as of January 1, 2017.
Some antibiotic use
category definitions
Prevention of Disease the use of an
antibiotic at a time of anticipated disease
occurrence so that animals in the
population do not contract the disease.
Control of Disease the use of an
antibiotic when a disease has been
detected in a population in order to stop
the spread of the disease.
Therapy of Disease administration of an
antibiotic to affect the course of clinical
disease.
Yearly sales data are
available
In kg for all antibiotic sales in the
U.S. with a food animal label.
2015 is our our last available report for
food animal sales.
But the last publically available human
data are from 2011.
The FDA Center for Veterinary
Medicine has just is requiring
estimates of species use in the
mandatory annual sales reporting
provided by pharmaceutical
companies for the 2016 data
RESISTANCE
CHALLENGE
S IN HUMAN
MEDICINE
2,049,442 23,488
Human vs. Animal Use
Comparison based on 2011 data
20,0 Not split out
63 in 2011,
2015
quantity
reported
 Food
Animal Human
Sales 2011 Sales 2011
Aminoglycosi
des 214,895 6,485
More Total Use
Lincosamides 190,101 71,455
by Food
Animals
Macrolides 582,836 164,028

Tetracyclines 5,652,855 113,832

Fluoroquinolone Facts
Labeled for individual animal
administration only in swine and cattle
Control and prevention claims
0.18% of 2014 sales (total kg of active
ingredient) of medically important
antimicrobials with a food animal label.
Any extralabel use is prohibited by law
Any use through the feed or water would be
illegal
Cephalosporin Facts
Labeled for individual animal administration in
swine, cattle, chicks, sheep, and goats.
Prevention and control labels
0.33% of 2014 sales (total kg of active
ingredient) of medically important antimicrobials
with a food animal label.
Extralabel use for another disease indication is
allowed (therapy and control only)
Label regimens are required
Extralabel regimens are prohibited
Any administration in the feed or water would be
illegal
General Food Animal Drug Facts
Any extralabel use in the feed is prohibited
Other extralabel use is only allowed under
the provisions of the Animal Medicinal Drug
Use Clarification Act (AMDUCA) regulations.
Veterinary-Client-Patient Relationship (VCPR)
required
As of January 1, 2017
All use of medically important antibiotics in the
feed or water of food animals must be authorized
by a veterinarian
Veterinary Feed Directive (VFD) for feed
Prescription for water
Disease Challenges in Food
Animals
Check out the PACCARB website for presentations
from the May 3-4, 2017 public meeting.
https://www.hhs.gov/ash/advisory-
committees/paccarb/meetings/past-
meetings/index.html
There are presentations on
Swine
Beef cattle
Dairy cattle
Broiler chickens
Aquaculture
Companion animals
Animal Agriculture
Evolution Today it takes less than 5 hogs
Cost and availability of to produce the same amount of
pork as 8 hogs back in 1959.
Land Water use is down 41%, land use
Animals required is down 78%, and the
carbon footprint is down 35% as
Feed evaluated from 1959 to 2009.
Fuel (pork.org)
In dairy production, the average
Labor yearly milk yield per cow in 1944
Water was 2,074 kg. In 2007, 9,093 kg.
dairy.ifas.ufl.edu/rns/2010/11-
Prevention and therapeutic
Bauman.pdfoptions
Regulation Comparing 1977 to 2007, U.S.
Consumers beef producers use 19% less
land, 33% less feed, 12% less
water, and 9% less fossil fuel per
pound of beef produced. The
carbon footprint is down 16%
 What is Stewardship?
1. Responsibility for appropriate
diagnostics and establishment of an
accurate and functional case En
N op

definition te
o:

r
St

5. Is this 2. Is there a non-antibiotic

antibiotic Yes alternative which will appropriately
intervention still prevent, control, or treat this disease
necessary? challenge?

not
If
4. Assuring use of the 3. Selection of an antibiotic
antibiotic as shown to which has been demonstrated
be safe and effective While to be safe and effective for this
purpose
Next Steps
The FDA CVM is currently evaluating
approximately 300 comments on in-feed
antibiotics with no defined duration of
administration.
https://www.federalregister.gov/document
s/2016/09/14/2016-21972/the-judicious-
use-of-medically-important-antimicrobial-
drugs-in-food-producing-animals-
establishing.
Next Steps
The USDA is conducting two on-farm
antibiotic use quantification projects this
year (beef feedlot and swine)
The FDA Center for Veterinary Medicine
has entered into two cooperative
agreements for on-farm antibiotic use
data collection in beef feedlots, dairy,
swine, and poultry.