Updates and Changes to Antibiotic Regulations
by Richard L. Wallace, DVM, MS, Dairy Extension Veterinarian, University of Illinois Extension
For over 50 years, antimicrobials have
been used on dairy farms along with other drugs to treat and control disease,
and to improve animal productivity. Recently, antibiotics have received an increasing
amount of attention. Initially, regulatory agencies were concerned about chemical
adulteration of milk and milk products with antibiotic residues. The public
health concern was that these residues may induce allergic reactions in sensitized
humans. The main concern today seems to focus on the concept that use of antimicrobials
on farms may contribute to antimicrobial resistance. This concept is extended
to imply that antimicrobial resistance observed in cattle pathogens may result
in human health problems.
The Food and Drug Administration, Center for Veterinary Medicine
(CVM) is concerned that the use of therapeutic antimicrobial drugs in food animals
will create antimicrobial drug resistance that could contribute to drug-resistant
human pathogen bacteria. These issues are being discussed with the U.S. Centers
for Disease Control and Prevention (CDC). Both the CVM and CDC have agreed on
the following points: 1) there is a legitimate need for both older and newer
antimicrobial drugs in animal agriculture, 2) the bulk of Salmonella, E.
coli O157, and Campylobacter infections in humans in the U.S. originate
from food of animal origin, and 3) the use of antimicrobials in animals will
cause resistance to develop, and there is a potential that resistant Salmonella,
E. coli, and Campylobacter will be transferred to humans through
The Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA)
spells out the rules and regulations veterinarians must follow when using drugs
in an extra-label manner. The Act all but excludes drug-compounding activities
by veterinarians and veterinary practices. Veterinary practitioners working
with livestock species must keep these new regulations in mind when administering
and dispensing medicinals. New antimicrobial drugs
have been approved and others have been made illegal or been voluntarily banned.
Practitioners must remain aware of these changing times. The integrity and leadership
of the veterinary profession will determine whether any antimicrobial product will maintain approved for use in livestock.
Aminoglycoside use in cattle receives additional voluntary ban
A resolution to ban the use of aminoglycosides
in cattle was passed by the American Veterinary Medical Association (AVMA) House
of Delegates in July 1998. The AVMA has now joined the American Association
of Bovine Practitioners, the Society for Theriogenology,
and the state veterinary medical associations from Wisconsin, Iowa, Kansas, and Michigan. The resolution supports a voluntary ban on the extra-label
use of aminoglycoside antibiotics, particularly gentamycin
in cattle. The ban is to remain in effect until further scientific information
The concern relates to the understanding that systemic use
of aminoglycosides present a potential conflict to standards
of practice because the scientific justification is limited. Residues can be
found in renal tissue for an undetermined, extended period of time. In order
to comply with AMDUCA regulations, extra-label drug use must include a sufficiently
extended withdrawal period so that no residues are found in meat of milk products.
Dairy producers using aminoglycosides and veterinarians
prescribing the use of aminoglycosides will be in
indefensible positions should residues be found.
Long acting tetracycline receives
lactating cow clearance
The Food and Drug Administration (FDA)
has approved the new animal drug application issued by Pfizer Animal Health
for the use of Liquamyacin LA-200 injection in lactating
dairy cattle. For the first time, dairy practitioners have an antibiotic approved
for systemic use when treating acute metritis. Milk taken from cows during treatment
with LA-200 and for 96 hours after the last treatment must not be used for food.
Coincident with this new approval comes
an amended tolerance for the combination of oxytetracycline, chlortetracycline
and tetracycline residues in milk. The Center for Veterinary Medicine (CVM)
has reevaluated toxicity and metabolism data used to establish oxytetracycline
tolerance levels. The previously accepted safe levels for oxytetracycline, chlortetracycline
and tetracycline in milk were 30, 30, and 80 ppb respectively for a sum of residues
of 140 ppb. The new combined tolerance level for tetracycline in milk is 300
ppb. With this increase, there are currently no FDA approved rapid screening
tests for tetracyclines in raw co-mingled milk. This
fact should be considered when evaluating milk from treated cows.
Fluoroquinolone receives approval from CVM
Enrofloxacin, a fluoroquinolone has been approved by the FDA, CVM for the
treatment of bovine respiratory disease associated with Pasteurella
and Haemophilus. The product, Baytril 100 Injectable Solution
is produced and distributed by Bayer Corporation and remains a prescription
product. Baytril is not for use in any class
of dairy cattle including veal calves. Extra-label use of fluoroquinolones
in food animals has been and is still prohibited by the FDA.
Fluoroquinolones are administered in human medicine for refractory
cases where other antibiotics have proven of little or no use. Bayer will be
conducting an intensive post-approval monitoring program to determine if use
of the product contributes to development of bacterial resistance to fluoroquinolones in cattle. The company has voluntarily committed
to the FDA to immediately take action, including removal of the Baytril from sale, should the FDA conclude that there is a
risk to public health. Veterinarians with a cavalier attitude toward extra-label
use of Baytril in lactating dairy cattle will not
only be violating the AMDUCA law, they will be jeopardizing the use of the product
for approved uses.
Nonsteroidal anti-inflammatory drugs prohibited as well
Phenylbutazone, known as "bute,"
is a veterinary drug only label-approved by the Food & Drug Administration
for use by veterinarians in dogs and horses. It has been associated with debilitating
conditions in humans and it is absolutely not permitted for use in food-producing
animals. USDA/FSIS has conducted a special project to for this drug in selected
bovine slaughter plants under federal inspection. An earlier pilot project by
FSIS found traces less than 3% of the livestock selected for testing, sufficient
cause for this special project. There is no tolerance for this drug in food-producing
livestock, and they and their by-products are condemned when it is detected.
Dairy producers must not use this drug in food-producing livestock and if it
is found, those producers will be subject to FDA investigation and possible
Are Now Prohibited
FDA is issuing an order prohibiting the extralabel
use of topical nitrofuran animal and human drugs in
food-producing animals. This order is based on evidence that extralabel use of topical nitrofuran
drugs in food-producing animals may result in the presence of residues that
are carcinogenic and have not been shown to be safe. A carbon-14 (C-14) radio-label
residue depletion study conducted by the FDA showed that detectable levels of
nitrofuran derivatives are present in edible tissues (milk,
meat, kidney, liver) of cattle treated by the ocular
(eye) route. The study indicates that use of these nitrofuran
products may pose a risk to public health because residues of known carcinogens
are present in edible tissues.
The current list of prohibited drugs includes furazolidone
and nitrofurazone, but it contains the parenthetical statement
(except for approved topical use). FDA plans to remove this parenthetical statement.
Once this prohibition is in place, the revised list will state that the following
drugs (both animal and human), families of drugs, and substances are prohibited
for extra-label uses in all food-producing animals.
- Diethylstilbestrol (DES)
- Other nitroimidazoles
- Furazolidone, Nitrofurazone, other
- Sulfonamide drugs in lactating dairy cattle (except
approved use of sulfadimethoxine, sulfabromomethazine, and sulfaethoxypyridazine)