Department of Health and Human Services
Public Health Service
Food and Drug Administration
San Francisco District
1431 Harbor Bay Parkway
Alameda. CA 94502-7070
Telephone: 510/337-6700
VIA FEDERAL EXPRESS
Our Reference: 1000135249
February 11, 2004
Ronald Hilarides, Managing Partner
Peter Schaafsma, Partner
S & H Dairy
4125 Bentley Road
Oakdale, California 95361-7935
WARNING LETTER
Dear Mssrs. Hilarides and Schaafsma:
An investigation of your dairy operation in Oakdale, California
conducted by Food and Drug Administration (FDA) investigators on
December 9 and 12, 2003, confirmed that you offered an animal for sale
for slaughter as food in violation of Sections 402(a)(2)(C)(ii) and
402(a)(4) of the Federal Food, Drug, and Cosmetic Act (the Act), 21
U.S.C. 342(a)(2)(C)(ii) and 342(a)(4). You also caused animal drugs to
become adulterated within the meaning of Section 501 (a)(5) of the Act,
21 U.S.C. 351, because the drugs were used in a manner that does not
conform with their approved use or the extralabel use regulations at
Title 21, Code of Federal Regulations, Part 530 (21 C.F.R. 530).
On or about October 9, 2003, you consigned a cow identified by United
States Department of Agriculture (USDA) laboratory report number 434889
to be slaughtered for human food to [redacted] USDA analysis of tissue
samples collected from that animal identified the presence of neomycin
at 18.85 parts per million (ppm) in the kidney. A tolerance of 7.2 ppm
has been established for residues of neomycin in cattle kidney at 21
C.F.R. 556.430. The presence of neomycin above established tolerance
levels in the edible tissues from this animal causes the food to be
adulterated within the meaning of Section 402(a)(2)(C)(ii) of the Act.
A food is adulterated under Section 402(a)(4) of the Act if it has been
prepared, packed, or held under insanitary conditions whereby it may
have been rendered injurious to health. As it applies in this case,
insanitary conditions means that you hold animals which are ultimately
offered for sale for slaughter as food under conditions whereby
medicated animals bearing possibly harmful drug residues could enter the
food supply. For example, our investigator observed the following:
1. Your firm fails to maintain a complete, written medication
treatment record system for your animals that includes all
treatments, the date of treatment, the amount of each drug
administered, the route of administration, and the person who
administered each drug;
2. Your firm fails to follow labeled directions for the following drugs:
a. [redacted]
The labeled directions specify that milk from treated cows must
not be used for food during the first 72 hours after calving.
However, FDA learned that you routinely allow newborn bull
calves, destined for slaughter, to suckle from dams that have
been treated with the [redacted] before the 72-hour withdrawal
period specified on the label.
b. [redacted]
The labeled directions state that no more than 10 mL [redacted]
should be injected at any one site in adult livestock. However,
you administer 30 mL [redacted] mixed with sterile water and
infuse this into the uterus of dairy cows with retained placenta.
3. Your firm fails to maintain a drug inventory/accountability system.
You adulterated animal drugs within the meaning of Section 501(a)(5) of
the Act when you failed to use the drugs in conformance with their
approved conditions or use or the extralabel use regulations at 21
C.F.R. 530. Extralabel use of animal drugs is permitted only on the
lawful order of a licensed veterinarian within the context of a valid
veterinarian-client-patient relationship and in compliance with the
criteria set forth at 21 C.F.R. 530. Because your use of the drugs
[redacted], [redacted], and [redacted] on your cattle did not conform
with the drugs' approved labeling or the extralabel use regulations, the
drugs are unsafe under Section 512(a) of the Act. As a result, your use
of these drugs caused them to be adulterated within the meaning of
Section 501(a)(5) of the Act.
The above is not intended to be an all-inclusive list of violations. As
a producer of animals offered for use as food, you are responsible for
assuring that your overall operations and the food you distribute are in
compliance with the laws.
It is not necessary for you to personally ship an adulterated animal in
interstate commerce to be responsible for a violation of the Act. The
fact that you caused the adulteration of an animal that was sold and
subsequently offered for sale to a slaughterhouse that ships in
interstate commerce is sufficient to hold you responsible for a
violation of the Act.
You should take prompt action to correct the above violations and to
establish procedures whereby such violations do not occur. Failure to do
so may result in regulatory action, such as a seizure and/or injunction,
without further notice.
You should notify this office in writing within 15 working days of
receipt of this letter of the steps you have taken to bring your dairy
into compliance with the law. Your response should include each step
being taken, that has been taken, or that will be taken to correct the
violations and prevent their recurrence. If corrective action cannot be
completed within 15 working days, state the reason for the delay and the
time frame within which the corrections will be completed. Please
include copies of any available documentation demonstrating that
corrections have been made.
Your response should be directed to: Ms. Harumi Kishida, Compliance
Officer, U.S. Food and Drug Administration, 1431 Harbor Bay Parkway,
Alameda, CA 94502-7070. If you have any questions regarding any issue in
this letter, please contact Ms. Kishida at (510) 337-6824.
Sincerely,
/s/
Roderick V. Asmundson for
Charles M. Breen
Acting District Director
San Francisco District
horizonal rule
http://www.fda.gov/foi/warning_letters/g4553d.htm
Department of Health and Human Services
Public Health Service
Food and Drug Administration
Los Angeles District
19701 Fairchild
Irvine, California 92612-2506
Telephone (949) 608-2900
WARNING LETTER
CERTIFIED MAIL
RETURN RECEIPT REQUESTED
February 9, 2004
W/L: 29-04
Phil Bauer
President
Phillips Cattle Company
345 N. Maple Dr., Ste. 296
Beverly Hills, CA 90210
Dear Mr. Bauer:
Our records reflect you are the president of Phillips Cattle Company
located at 910 Nichols Road, El Centro, CA. An investigation of your
feedlot operation conducted by our investigator on December 8 and 9,
2003, confirmed that you offered animals for sale for slaughter as food
which is in violation of Sections 402(a)(2)(C)(ii) and 402(a)(4) of the
Federal Food, Drug, and Cosmetic Act (henceforth the Act).
A food is adulterated under Section 402(a)(2)(C)(ii) of the Act if it
contains a new animal drug that is unsafe within the meaning of Section
512 of the Act. A food is further adulterated under Section 402(a)(4) of
the Act if it has been held under conditions whereby it may have been
rendered injurious to health.
On or about August 8, 2003, you sold a culled beef cow identified by
USDA Laboratory report 256547 for slaughter as human food. USDA analysis
of tissue samples collected from that animal identified the presence of
tilmicosin in the liver at 06.90 parts per million (ppm), in the muscle
at 0.94 ppm and in the kidney at 9.13 ppm. A tolerance of 1.20 ppm in
the liver and 0.10 ppm in the muscle has been established for residues
of tilmicosin in cattle. There is no tolerance for tilmicosin in the
kidney of cattle [21 CFR 556.735].
Our investigation also found that you hold animals under improper
conditions whereby diseased animals and/or medicated animals bearing
potentially harmful drug residues are likely to enter the food supply.
For example, you lack an adequate system for assuring that animals
medicated by you have been withheld from slaughter for the appropriate
periods of time to permit depletion of potentially hazardous residues of
drugs from edible tissues. Foods from animals held under such conditions
are considered adulterated under the Act.
It was further determined that you are using drugs in a manner contrary
to their approved labeling. Such extra-label use is not permitted,
except by or on the lawful written or oral order of a licensed
veterinarian within the context of a valid veterinarian-client-patient
relationship, and otherwise in compliance with the limitations set forth
for specific extra-label uses [21 CFR 530.10 and 530.11]. Your use of
drugs in any manner other than as labeled causes those drugs to bs:
adulterated under Section 501 (a)(5) of the Act because there is no
approval for such use as required by Section 512 (a)(1)(B) of the Act.
*
You are adulterating injectable tilmicon , such as [redacted] that
you use on cattle in a manner contrary to the approved labeling.
Injectable tilmicosin is labeled with a 28 day withdrawal time.
Culling an animal for slaughter 2 days after treatment with
tilmicosin does not conform to the approved labeling.
*
You are adulterating injectable penicillin, such as [redacted]
that you use on cattle in a manner contrary to the approved
labeling. The labeled instructions are 1 cc per 100 pounds of body
weight. Your use of 30 ccs per 800 pound animal does not conform
to the approved labeling.
The above is not intended to be an all-inclusive list of violations. As
a producer of animals, which are offered for use as food, you are
responsible for assuring that your overall operations and the food you
distribute are in compliance with the law.
Please note that it is not necessary for you to personally ship an
adulterated animal in interstate commerce to be responsible for a
violation of the Act. The fact that you caused the adulteration of an
animal that was sold to a slaughterhouse which ships in interstate
commerce is sufficient to hold you responsible for a violation of the Act.
Additionally, it is not necessary for you to have an illegal drug
residue in an animal to violate the law. We have reviewed your treatment
protocols as presented to our investigator and have the following
comments. All drugs are labeled with specific instructions on the dosage
and route of administration as well as the disease or condition to be
treated. Any deviation from the approved labeling is a violation of the
law. For example, your protocol indicates you are using [redacted]
without a withdrawal time. [redacted] is labeled with a 35 day
withdrawal time. Your shipment of any animal treated with [redacted]
prior to the 35 day withdrawal time is a violation of the law. Secondly,
your protocol indicates that you are using a 28 day withdrawal for
[redacted]. While this is the correct withdrawal time for intra-muscular
injection, when [redacted] is administered subcutaneous there is a 38
day withdrawal time. Also we note that your protocols identify both
[redacted]. These are two different forms of the drug and have different
dosages and withdrawal times. Your treatment records and protocols
should reflect this difference. Your protocol identifies a 2 day
withdrawal time for [redacted]. This is incorrect. [redacted] when used
as directed has a 4 day withdrawal time.
Review of the prescription forms presented to our investigator reveals
that [redacted] has identified a 28 day withdrawal for [redacted]
administered subcutaneously. The labeled withdrawal time as stated above
is 38 days. As stated above, extra-label use of new animal drugs is
authorized only when there is a valid veterinarian-client-patient
relationship. A valid veterinarian-client-patient relationship can exist
only where, among other requirements, a licensed and practicing
veterinarian has recently seen and is personally acquainted with the
keeping and care of the animals by virtue of examination of the
animal(s), and/or by medically appropriate and timely visits to the
premises where the animal(s) are kept. See 21 CFR 530.4(i). Our
investigator noted that [redacted] address is located in Texas and that
the prescription form appears to have originated from Texas. The
distance between [redacted] Texas address and the California lot where
the animals are kept raises questions about his ability and availability
to visit, care for, and examine the animals in the manner required by
the regulations. We recommend you evaluate your current veterinary
pactices.
Additionally, we strongly suggest you review your treatment protocols
with your veterinarian, university extension services or state animal
health officials to assure that you are using all medications in a legal
and effective manner.
You should take prompt action to correct the above violations and to
assure that the procedures you have established will prevent their
recurrence. Failure to do so may result in regulatory action, such as
injunction, without further notice. This letter constitutes official
notification under the law and provides you an opportunity to correct
the violations.
Please advise this office in writing within fifteen (15) working days of
receipt of this letter of the steps you have taken to bring your dairy
into compliance with the law. Your response should include each step
that has been taken to correct the violations and prevent their
recurrence. If corrective action cannot be completed within fifteen (15)
working days, state the reason for the delay and the time within which
such corrections will be made. If you have any questions or , need
clarifications regarding this letter prior to your written response, you
may contact Barbara Rincon, Compliance Officer at telephone number (949)
608-4439.
Your written response should be directed to:
Acting Director, Compliance Branch
U.S. Food and Drug Administration
19701 Fairchild
Irvine, CA 92612
Sincerely,
/s/ Alonza E. Cruse
District Director
cc: Ross Jenkins
General Manager
Phillips Cattle Co.
505 E. Barioni
Imperial, CA 92551
Lonnie Foster
Yard Manager
Phillips Cattle Co.
910 Nichols Rd.
El Centro, CA 92243
http://www.fda.gov/foi/warning_letters/g4554d.htm
a few more warning letters ;
NTIBIOTIC/HORMONE USE IN FARM ANIMALS
2. now what about those antibiotic and hormone use in cattle?
let us take a look at just this weeks warning letters, and
what about those 200,000 DOWNER CATTLE IN THE USA. how many
reach the consumers plate? well here is one that did;
On or about August 22, 2002, you sold a downer cow to [redacted] number
842 ET. This cow was subsequently identified on analysis of tissue
samples collected from this animal identified the presence of
Oxytetracycline at 8.47 ppm in the liver and 3.20 ppm in muscle tissue.
The maximum allowable tolerance for Oxytetracycline in cattle is 6 ppm
in the liver and 2 ppm in muscle tissue. In addition, Sulfadimethoxine
was found at 12.03 ppm in the liver and at 5.83 ppm in muscle tissue.
The maximum tolerance for Sulfadimethoxine in edible tissue of cattle is
0.1 ppm....
full text;
January 22, 2003
VIA CERTIFIED MAIL
RETURN RECEIPT REQUESTED
In reply refer to Warning Letter SEA 03-13
Jose L. Lourenco, Owner
Lourenco Dairy #2
19524 U.S. Highway 30
Buhl, Idaho 83316
WARNING LETTER
Dear Mr. Lourenco:
An investigation at your dairy located at 19524 U.S. Highway 30, Buhl,
Idaho, by our investigators on December 12, 2002 , confirmed that you
offered animals for sale for slaughter as food in violation of Section
402(a)(2)(C)(ii), and 402(a)(4) of the Federal Food, Drug, and Cosmetic
Act (the Act).
A food is adulterated under Section 402(a)(2)(C)(ii) of the Act if it
contains a new animal drug that is unsafe within the meaning of Section
512 of the Act. From July 22, 2002 to August 29, 2002, you sold cull
dairy cows for slaughter as human food to. Some of the cows had illegal
tissue residues asfollows:
1. On or about July 22, 2002, you sold a culled dairy cow to [redacted]
with no tag. The cow was subsequently tagged as carcass tag 659, and
identified on USDA form #433453. USDA analysis of tissue samples
collected from the cow identified the presence of Sulfadimethoxine at
2.12 parts per million (ppm) in the liver, and 1.52 ppm in muscle
tissue. The maximum allowable tolerance for Sulfadimethoxine in edible
tissue of cattle is .l ppm. In addition, this animal was found to
contain Tilmicosin at 16.90 ppm in the liver and 16.70 ppm in the
kidney. The maximum allowable tolerance for Tilmicosin in edible tissue
of cattle is 1.2 ppm.
2. On or about August 12, 2002, you sold a culled dairy cow with tag
number 1222 ET to [redacted]. This cow was subsequently identified on
USDA form # 433458. USDA analysis of tissue samples collected from this
animal identified the presence of Penicillin at .98 ppm in the kidney
and at .47 ppm in the liver. The maximum allowable tolerance for
Penicillin in edible tissue of cattle is 0.05 ppm.
3. On or about August 22, 2002, you sold a downer cow to [redacted]
number 842 ET. This cow was subsequently identified on analysis of
tissue samples collected from this animal identified the presence of
Oxytetracycline at 8.47 ppm in the liver and 3.20 ppm in muscle tissue.
The maximum allowable tolerance for Oxytetracycline in cattle is 6 ppm
in the liver and 2 ppm in muscle tissue. In addition, Sulfadimethoxine
was found at 12.03 ppm in the liver and at 5.83 ppm in muscle tissue.
The maximum tolerance for Sulfadimethoxine in edible tissue of cattle is
0.1 ppm.
4. On or about August 22, 2002, you sold a culled dairy cow to
[redacted] with ear tag number 718. This cow was subsequently identified
on USDA form 433459. USDA analysis of tissue samples collected from this
animal identified the presence of Penicillin at .84 ppm in the kidney.
The maximum tolerance for penicillin in edible tissue of cattle is 0.05
ppm. In addition, USDA found Sulfadimethoxine 6.41 ppm in the liver and
at 3.32 ppm in muscle tissue. The maximum allowable tolerance for
Sulfadimethoxine in edible tissue of cattle is 0.1 ppm.
5. On or about August 29, 2002, you sold a culled dairy cow to
[redacted] with no ear tag. The cow was subsequently identified with
carcass tag number 282, and identified on USDA form #433461. USDA
analysis of tissue samples collected from this animal identified the
presence of Penicillin at .77 ppm in the kidney and .38 in the liver.
The maximum tolerance for penicillin in edible tissue of cattle is 0.05
ppm.
A food is adulterated under Section 402(a)(4) of the Act "if it has been
prepared, packed, or held under insanitary conditions...~ hereby it may
have been rendered injurious to health." As it applies in this case,
"insanitary conditions" means that you hold animals which are ultimately
offered for sale for slaughter as food under conditions which are so
inadequate that medicated animals bearing possibly harmful drug residues
are likely to enter the food supply.
For example, our investigator noted the following conditions on your farm:
1. You failed to maintain medication records which identify the animal,
the date of medication, the drug, the dosage administered and the
pre-slaughter withdrawal time.
2. You failed to follow label directions for medications you
administered to your animals in that you failed to follow the labeled
pre-slaughter withdrawal times.
3. You failed to have a system of reviewing treatment records prior to
offering an animal for slaughter for human food, to assure that drugs
had been used only as directed and that the appropriate withdrawal times
had been observed.
4. You failed to have a valid veterinarian prescription for the use of
Penicillin in an Extra-label manor.
Our investigation revealed that the Penicillin residue came from your
use of Over the Counter Penicillin at dosages above the labeled amount
on your dairy herd. The use of Penicillin at amounts greater than that
stated on the label requires a valid prescription from a licensed
veterinarian. Your extra label use of Penicillin is a deviation from
Title 21, Code of Federal Regulations (21 CFR), Part 530, Extra label
Drug Use in Animals, which causes certain animal drugs used to medicate
food producing animals, to be adulterated within the meaning of Section
501(a)(5) of the Act, in that they are new animal drugs which are unsafe
within the meaning of Section 512(a)(4).
In October of 1994, Congress passed the Animal Medicinal Drug Use
Clarification Act, which permits extra-label use under certain
controlled conditions, specified in 21 CFR Part 530. Extra label use is
only permitted if the use is by or on the lawful order of a licensed
veterinarian within the context of a valid veterinarian/client/patient
relationship and in conformance with criteria set forth in Part 530.
We request that you take prompt action to ensure that dairy cows and
calves which you offer for sale as human food will not be adulterated
with drugs or contain illegal residues.
Introducing adulterated foods into interstate commerce is a violation of
Section 301(a) of the Act.
Causing the adulteration of drugs after receipt in interstate commerce
is a violation of Section 301(k) of the Act.
You should be aware that it is not necessary for you to have personally
shipped an adulterated animal into interstate commerce to be responsible
for a violation of the Act. The fact that you offered an adulterated
animal to be slaughtered into food for human consumption where it was
held for sale in interstate commerce is sufficient to make you
responsible for violations of the Act.
The above is not intended to be an all-inclusive list of violations. As
a producer of animals offered for use as food, you are responsible for
assuring that your overall operations and the foods you distribute are
in compliance with the law.
You should take prompt action to correct the above violations and to
establish procedures whereby such violations d o not recur. Failure to d
o so may result in regulatory action without further notice such as
seizure and/or injunction.
Within fifteen (15) days of the receipt of this letter, notify this
office in writing of the specific steps you have taken to correct these
violations and preclude their recurrence. If corrective action cannot be
complete d within fifteen working days, state the reason for the delay
and the time frame within which corrections will b e completed.
Please send your reply to the Food and Drug Administration, Attention:
Bruce Williamson, Compliance Officer, 22201 23rd Drive SE, Bothell, WA
98021. If you have questions regarding any issue in this letter, please
contact Bruce Williamson, Compliance Officer, at (425) 483-4976.
Sincerely,
/s/
Charles M. Breen
District Director
http://www.fda.gov/foi/warning_letters/g3808d.htm
WARNING LETTER
January 22, 2003
CERTIFIED MAIL
RETURN RECEIPT REQUESTED
W/L# 18-03
Arthur H. Marquez
Owner
Marquez Dairy LLC
7360 Pine Ave.
Chino, CA 91710
Dear Mr. Marquez:
An investigation at your dairy operation located at 7360 Pine Avenue
Chino California, conducted by our investigators on November 13, 2002,
confirmed that you offered animals for sale for slaughter as food in
violation of Sections 402(a)(2)(C)(ii) and 402(a)(4) of the Federal
Food, Drug, and Cosmetic Act (henceforth the "Act").
A food is adulterated under Section 402(a)(2)(C)(ii) of the Act if it
contains a new animal drug that is unsafe within the meaning of Section
512 of the Act. A food is further adulterated under Section 402(a)(4) of
the Act if it has been held under conditions whereby it may have been
rendered injurious to health.
On or about August 5, 2002, you sold a culled dairy cow identified by
USDA Laboratory report 427797 for slaughter as human food. USDA analysis
of tissue samples collected from that animal identified the presence of
sulfadimethoxine in the muscle at 11.24 parts per million (ppm) and in
the liver at 14.80 ppm. A tolerance of 0.1 ppm has been established for
residues of sulfadimethoxine in the edible tissues of cattle. (Title 21,
Code of Federal Regulations, Section 556.640).
Our investigation also found that you hold animals under improper
conditions whereby diseased animals and/or medicated animals bearing
potentially harmful drug residues are likely to enter the food supply.
For example, you lack an adequate system for assuring that animals
medicated by you have been withheld from slaughter for the appropriate
periods of time to permit depletion of potentially hazardous residues of
drugs from edible tissues. Foods from animals held under such conditions
are considered adulterated under the Act.
Please note that it is not necessary for you to personally ship an
adulterated animal in interstate commerce to be responsible for a
violation of the Act. The fact that you caused the adulteration of an
animal that was sold to a slaughterhouse that ships in interstate
commerce is sufficient to hold you responsible for a violation of the Act.
The above is not intended to be an all-inclusive list of violations.
Government records available to us indicate there have been other
occasions when you have offered drug-adulterated animals for sale as
human food. As a producer of animals, which are offered for use as food,
you are responsible for assuring that your overall operations and the
food you distribute are in compliance with the law.
You should take prompt action to correct the above violations and to
assure that the procedures you have established will prevent their
recurrence. Failure to do so may result in regulatory action, such as
injunction, without further notice. This letter constitutes official
notification under the law and provides y ou an opportunity to correct.
Please advise this office in writing within fifteen (15) working days of
receipt of this letter of the steps you have taken to bring your dairy
into compliance with the law. Your response should include each step
that has been taken to correct the violations and prevent their
recurrence. If corrective action cannot be taken within fifteen (15)
working days, state the reason for the delay and the time within which
such corrections will be made. If you have any questions or need
clarifications regarding this letter prior to your written response, you
may contact Barbara Rincon, Compliance Officer at telephone number (949)
798-7739.
Your written response should be directed to:
Robert B. McNab
Acting Director, Compliance Branch
U.S. Food and Drug Administration
19900 MacArthur Blvd., Ste. 300
Irvine, CA 92612-2445
Sincerely,
/s/
Alonza E. Cruse
District Director
http://www.fda.gov/foi/warning_letters/g3807d.htm
January 13, 2003
VIA CERTIFIED MAIL
RETURN RECEIPT REQUESTED
In reply refer to Warning Letter SEA 03-11
Dale C. Devries, Owner
Thomas R. Devries, Owner
Devries Family Farm LLC
15720 Highway 24
Moxee, Washington 98936
WARNING LETTER
Dear Messrs. Devries:
An investigation at your dairy located at 15720 Highway 24, Moxee,
Washington, by our investigator on November 20-21, 2002, confirmed that
you offered animals for sale for slaughter as food in violation of
Section 402(a)(2)(C)(ii) and 402(a)(4) of the Federal Food, Drug, and
Cosmetic Act (the Act).
A food is adulterated under Section 402(a)(2)(C)(ii) of the Act if it
contains a new animal drug that is unsafe within the meaning of Section
5 12 of the Act.
On May 13, 2002, you delivered a holstein cow with back tag #91 TO 376
identified on USDA Case #01-1852-WA, Form #431002, to [redacted] sold
this holstein cow for slaughter as human food to [redacted] does not
medicate the animals. USDA analysis of tissue samples collected from
that animal identified the presence of sulfadimethoxine in the liver at
1.51 parts per million (ppm), and in the muscle at 1.84 ppm.
A tolerance of 0.1 ppm has been established for residues of
sulfadimethoxine in edible tissues of cattle (Title 21 Code of Federal
Regulations 556.640). This excess residue of sulfadimethoxine in edible
tissue from this animal causes the food to be adulterated.
A food is adulterated under Section 402(a)(4) of the Act "if it has been
prepared, packed, or held under insanitary conditions . . .whereby it
may have been rendered injurious to health." As it applies in this case,
"insanitary conditions" means that you hold animals which are ultimately
offered for sale for slaughter as food under conditions that are so
inadequate that medicated animals bearing potentially harmful drug
residues are likely to enter the food supply. For example, you lack an
adequate system for assuring that animals to which you administer
medication have been withheld from slaughter for appropriate periods of
time to deplete potentially hazardous residues of drugs from edible
tissues; you have no animal medication records that would identify which
animal had been medicated, what date the medication was administered,
what dosage of medication had been used, and what the withdrawal times
should be; and you lack an adequate system for ,assuring that drugs are
used in a manner not contrary to the directions contained in their
labeling.
It is not necessary for you to personally ship an adulterated animal in
interstate commerce to be responsible for a violation of the Act. The
fact that you caused the adulteration of an animal that was sold and
subsequently offered for sale to a slaughterhouse that ships in
interstate commerce is sufficient to hold you responsible for a
violation of the Act.
The above is not intended to be an all-inclusive list of violations. As
a producer of animals offered for use as food, you are responsible for
assuring that your overall operations and the foods you distribute are
in compliance with the law.
You should take prompt action to correct the above violations and to
establish procedures whereby such violations do not recur. Failure to do
so may result in regulatory action without further notice. These actions
may include, but are not limited to, seizure and/or injunction.
You should notify this office in writing, within fifteen (15) working
days of the receipt of this letter, of the specific steps you have taken
to bring your firm into compliance with the law. If corrective action
cannot be completed within 15 working days, state the reason for the
delay and the time frame within which the corrections will be completed.
Please include copies of any available documentation demonstrating that
corrections have been made.
Please send your reply to the Food and Drug Administration, Attention:
Lisa M. Elrand, Compliance Officer, 2220 1 23rd Drive SE, Bothell,
Washington 98021-4421. If you have questions regarding any issue in this
letter, please contact Lisa M. Elrand, Compliance Officer, at (425)
483-4913.
Sincerely,
/s/
Charles M. Breen
District Director
http://www.fda.gov/foi/warning_letters/g3803d.htm
December 15, 3003
CERTIFIED MAIL
RETURN RECEIPT REQUESTED
WARNING LETTER
Ref. KAN 2003-04
Charles L. Vander Ploeg
President/CEO
Vet Pharm. Inc.
39215th Street N.E.
P.O. Box 167
Sioux Center, IA 51250
Dear Mr. Vander Ploeg:
Recently an inspection was made of your veterinary drug sales facility
located at the above address. This inspection was conducted from
September 11 to 13, 3002, by a Food and Drug Administration Investigator
from this office who documented sales of prescription drugs for
veterinary use that are adulterated within the meaning of Section
501(a)(5) of the Federal Food, Drug and Cosmetic Act (Act) and
misbranded within the meaning of Section 502(f)(1) of the Act.
The drugs "Amoxil Amoxicillin For Oral Suspension" and "Sulfamethoxazole
and Trimethoprim Oral Suspension USP" among others, are human drugs that
are being dispensed for animal use without the required Labeling.
including adequate directions for use.
Under Section 512(a)(5), a drug approved for human use may be used in
animals if its use or intended use is on the lawful order of a
veterinarian and is in compliance with the regulations at 21 CFR Part
530. The human drugs you are dispensing for use in animals are not in
compliance with 21 CFR 530.12 because they do not bear the required
labeling information.
Because your products do not comply with the applicable regulations.
they are unsafe within the meaning of Section 512(a) and are thus
adulterated under Section 501(a)(5).
In addition. prescription veterinary drugs intended for extralabel use
which you are dispensing are not in compliance with 21 CFR 520.12
because they do not bear the required labeling information. Because
these products do not comply with the applicable regulations, they are
also unsafe within the meaning of Section 512(a) and thus adulterated
under Section 501(a)(5).
Finally, because your products are dispensed without adequate directions
for use. they are misbranded under Section 502(f)(1).
You should take prompt action to correct these violations end to
establish procedures co prevent their recurrence at any of the
established locations within your company. Failure to promptly correct
these violations may result in regulatory action without further notice.
such as seizure and/or injunction.
The violations listed above are not intended co be all-inclusive. You as
a corporate official of this firm. have a responsibility to insure that
all drugs intended for veterinary use, which bear the human or
veterinary prescription legend, are sold by you or your firm properly
labeled as required.
It is necessary for you to take action on this matter now. Please let
this office know in writing within fifteen ( 15) working Jays from the
dare you received this letter what steps you are taking to correct the
problems. We also ask chat you explain how you plan to prevent this from
happening again. If you need more time, let us know why and when expect
to complete your correction.
Your reply should k sent to Clarence R. Pendleton, Compliance Officer,
at the above address.
Sincerely,
/s/
Charles W. Sedgwick
District Director
Kansas City District
http://www.fda.gov/foi/warning_letters/g3801d.htm
a few more of 100s;
SNIP...
Our investigation also found that you hold animals under
conditions which are so inadequate that medicated animals bearing
potentially harmful drug residues are likely
to enter the food supply....
SNIP...
http://www.fda.gov/foi/warning_letters/g2075d.pdf
may take some time to load, but worth reading.
check all the different antibiotics;
anitresistance antibiotics and animals usda
http://www.aphis.usda.gov/vs/ceah/cei/antiresist.entire.pdf
Medicated Feeds
http://63.75.126.221/scripts/wlcfm/subject.cfm?FL=M
Illegal Drug Residue/Adulterated
http://63.75.126.221/scripts/wlcfm/subject.cfm?FL=I
Illegal Drug Tissue Residue
http://63.75.126.221/scripts/wlcfm/subject.cfm?FL=I
Drug Residues/Edible Tissues/Adulterated
http://63.75.126.221/scripts/wlcfm/subject.cfm?FL=D
examples;
snip...
USDA testing revealed the presence of 0.23 ppm
(parts per million) penicillin in the kidney
tissue of the animal. This is considered to be
illegal tissue residue since the tolerance for
penicillin in edible bovine tissue is 0.05 ppm.
The presence of penicillin in the edible tissue
from your animal at the concentration level detected
renders the food from the animal to be adulterated
under section blah blah blah....
snip...
http://www.fda.gov/foi/warning_letters/m2268n.pdf
http://www.fda.gov/foi/warning_letters/g1225d.pdf
look under subject here;
http://63.75.126.221/scripts/wlcfm/sindex.cfm
or this url and search;
http://www.fda.gov/foi/warning.htm
most recent;
Van Haitsma Dairy Farm 12/14/01
Detroit District Office
Illegal Drug Tissue Residue/Adulterated
View File
http://www.fda.gov/foi/warning_letters/g2040d.pdf
more data on MRSA and VRSA;
LANCET
Volume 350, Number 9092
06 December 1997
Commentary
Vancomycin-resistant Staphylococcus aureus:
apocalypse now?
http://www.thelancet.com/
http://jama.ama-assn.org/issues/v283n5/ffull/jwr0202-1.html
http://wonder.cdc.gov/wonder/prevguid/m0049042/m0049042.asp
http://www.cdc.gov/ncidod/hip/ARESIST/mrsahcw.htm
http://www.scotland.gov.uk/library2/doc15/sim-01.asp
http://www.mbiotech.com/newsreleases/nr112800.htm
http://www.dent.ucla.edu/pic/members/antibiotics/vancomycin.html
http://www.nlm.nih.gov/medlineplus/druginfo/vancomycinsystemic202590.html
Greetings again Codex,
P.S. lot of very sick cattle pumped up with antibiotics and hormones ;
Thomas, Allan
5/06/04
Seattle District Office Illegal Drug Residue in Animal Tissue/Extralabel
Drug Use/Adulterated [PDF]
HTML:
No
Milk Source, LLC
5/05/04
Minneapolis District Office Illegal Drug Residue in Animal
Tissue/Extralabel Drug Use/Adulterated/Misbranded [PDF]
[HTML]
No
New Horizons Dairy LLC
4/29/04
Chicago District Office Illegal Drug Residue in Animal Tissue/Extralabel
Drug Use/Adulterated [PDF]
[HTML]
No
Daley Farms, LLP
4/23/04
Minneapolis District Office Illegal Drug Residue, Animal Tissue/Extra
Label Drug Use [PDF]
[HTML]
No
Lyrek Farms
4/22/04
Minneapolis District Office Illegal Drug Residue in Animal
Tissue/Extralabel Drug Use/Adulterated [PDF]
[HTML]
No
Schultze, Frederick R.
4/07/04
New England District Office Illegal Drug Residue in Animal
Tissue/Extralabel Drug Use/Adulterated [PDF]
[HTML]
No
Wadleigh's Falls Veterinary Clinic
4/07/04
New England District Office Illegal Drug Residue in Animal
Tissue/Extralabel Drug Use/Adulterated [PDF]
[HTML]
No
Hillcrest Dairy, LLC
3/17/04
San Francisco District Office Illegal Drug Residue in Animal
Tissue/Extralabel Drug Use/Adulterated [PDF]
[HTML]
No
SEEMS to me greed is fueling this as it did BSE aka
mad cow disease...
In Reply to: Groups debate US plan on antibiotics for animals and one brain dead pig farmer $$$ posted by TSS on October 4, 2002 at 2:25 pm:
RESTRICT ANTIBIOTIC USE IN ANIMALS: SCIENTISTS
A federal science panel is calling for a crackdown in the use of
antibiotics on farm animals. The panel says antibiotic-resistant
bacteria is developing in humans because of what we eat.
FULL STORY:
http://cbc.ca/stories/2002/10/07/Consumers/antibiotics_021007
RESTRICT ANTIBIOTIC USE IN ANIMALS: SCIENTISTS
http://www.accessdata.fda.gov/scripts/wlcfm/subject.cfm?FL=E
Perspectives
Use of Antimicrobial Growth Promoters in Food Animals and Enterococcus faecium Resistance to Therapeutic Antimicrobial Drugs in Europe
Henrik C. Wegener, Frank M. Aarestrup, Lars Bogø Jensen, Anette M. Hammerum, and Flemming Bager
Danish Veterinary Laboratory, Copenhagen, Denmark
--------------------------------------------------------------------------------
Supplementing animal feed with antimicrobial agents to enhance growth has been common practice for more than 30 years and is estimated to constitute more than half the total antimicrobial use worldwide. The potential public health consequences of this use have been debated; however, until recently, clear evidence of a health risk was not available. Accumulating evidence now indicates that the use of the glycopeptide avoparcin as a growth promoter has created in food animals a major reservoir of Enterococcus faecium, which contains the high level glycopeptide resistance determinant vanA, located on the Tn1546 transposon. Furthermore, glycopeptide-resistant strains, as well as resistance determinants, can be transmitted from animals to humans. Two antimicrobial classes expected to provide the future therapeutic options for treatment of infections with vancomycin-resistant enterococci have analogues among the growth promoters, and a huge animal reservoir of resistant E. faecium has already been created, posing a new public health problem.
Vancomycin-Resistant Enterococcus faecium (VRE)
In addition to being a member of the normal gut flora of nearly all warm-blooded animals (including humans), E. faecium has the ability to cause a wide range of infections, primarily serious infections in hospital patients (particularly in intensive care units). Increasing incidence of E. faecium infections has been associated with use of third-generation cephalosporins in hospitals (1). Enterococci are resistant to many antibiotics. In an increasing number of cases, vancomycin is the only treatment drug that remains effective. Because E. faecium was untreatable with practically all other antibiotics, the emergence of the first high level vancomycin-resistant E. faecium was of particular concern (2). By 1997, more than 15% of nosocomial enterococcal infections in U.S. hospitals were due to VRE (3).
The vancomycin-resistant strain of E. faecium (VRE) contains the VanA gene cluster located at a mobile genetic element, a transposon designated Tn1546. Although other mechanisms and determinants of glycopeptide resistance have been found in E. faecium, in this article, VRE will refer to strains containing the vanA gene and Tn1546. First isolated in France in 1986, VRE were subsequently found in the United States in 1989, where they rapidly became a frequent cause of hospital infections (3). Like many other nosocomial pathogens, VRE were believed to originate and be maintained in hospitals and to have little, if any, association with the community. Nosocomial outbreaks and clonal spread in the United States supported this assumption (4). In Europe, however, even though serious incidents have occurred in some countries, VRE-associated hospital infections have not increased at the same rate and to the same proportion as in the United States (5). The first indication that the epidemiology of VRE may differ from that of other gram-positive organisms capable of causing hospital infections (e.g., methicillin-resistant Staphylococcus aureus) came from the United Kingdom, where Bates et al. (6) reported isolating VRE from pig herds as well as from the farm environment. These scientists suggested that a community source of VRE may exist. Soon afterwards, Klare et al. (7) in Germany showed that VRE could be cultured frequently from pigs, poultry, and humans in the community and suggested that VRE may be associated with the use of glycopeptides as growth promoters in food animals.
Antimicrobial Growth Promoters
Antimicrobial growth promoters (AGPs) are antibiotics added to the feed of food animals to enhance their growth rate and production performance. The mechanism by which AGPs work is not clear. AGPs reduce normal intestinal flora (which compete with the host for nutrients) and harmful gut bacteria (which may reduce performance by causing subclinical disease). The effect on growth may be due to a combination of both fewer normal intestinal flora and fewer harmful bacteria. The class of antimicrobial drugs used and the animal species involved may determine the relative importance of each mechanism (8). The quantity used in feed varies with each antimicrobial agent. In the European Union (EU), avoparcin 20 mg/kg and 40 mg/kg was approved for different age groups of pigs and chickens; the concentration is often referred to as "subtherapeutic" (not to be confused with sub-MIC levels). The resulting concentration in the gastrointestinal tract of the animal is sufficient to inhibit the susceptible bacteria and markedly affect the composition of the bacterial gut flora (8).
In Denmark, as well as in other countries, only a few glycopeptides have been used; for humans vancomycin and (to a lesser extent) teicoplanin have been used, and for animals avoparcin has been used exclusively as a feed additive for growth promotion. Avoparcin has not been used in animals in Sweden since 1986 because of a national prohibition of AGPs; in the United States, avoparcin was never approved because of its carcinogenic effects (9).
Few countries have accurate data on the use of antibiotics in animals and humans. In Denmark, 24 kg of active vancomycin was used for human therapy in 1994. In comparison, 24,000 kg of active avoparcin was used as a feed additive for animals (10). In Austria, an average of 582 kg of vancomycin was imported for medical purposes and 62,642 kg of avoparcin for animal husbandry per year from 1992 to 1996 (11). Thus, although there are more food animals than humans, the selective pressure favoring VRE in Europe can be estimated to be much higher in food animals than in humans. Data on the yearly use of vancomycin in the United States and in major European countries were recently published by Kirst et al. (12). Denmark, a small country, used more glycopeptide growth promotant (avoparcin) than all of Europe and the United States used for treating ill humans (vancomycin). Difference in denominators implies huge difference in use (10).
Use of Avoparcin as a Growth Promoter and the Occurrence of VRE in Food Animals
The high selective pressure by the use of glycopeptides as growth promoters could explain the presence of VRE in food animals. We have conducted a number of studies to investigate the association between the use of avoparcin as a growth promoter and the occurrence of VRE.
In one study, eight poultry flocks raised conventionally and six raised without growth promoters were compared (13). No VRE was found in birds raised without growth promoters, whereas five out of eight conventional flocks contained VRE. Isolation rates in positive flocks were as follows: of five fecal samples tested, one to four (20%–80%) were positive. Twenty-two pig herds and 24 poultry flocks, half of which had used avoparcin and half of which had not, were compared by occurrence of VRE in fecal samples collected from animals of the herds and flocks. A strong and statistically highly significant association between the presence of VRE and the use of avoparcin was observed (14). Of 12 pig herds using feed with avoparcin, 8 had VRE, while of 10 herds not using avoparcin, 2 had VRE (p = 0.043, risk ratio [RR] 3.3; 95% confidence interval [CI]: 1.1, 10.0). In broiler farms where avoparcin was used, VRE was isolated from 11 of 12 fecal samples. In farms where avoparcin was not used, VRE was isolated in 2 of 12 samples (p <0.0006; RR 5.5; 95% CI: 2.2, 13.9).
The association observed at the flock and herd level has also been observed at the country level. In countries where avoparcin had been used as a growth promoter, VRE could frequently be cultured from food animals, whereas in countries where avoparcin had not been used, VRE were not detected (Table 1). These findings are consistent with the hypothesis that use of avoparcin has created a reservoir for VRE in food animals.
Table 1. Avoparcin as a growth promoter
in countries where the occurrence of
vancomycin-resistant enterococci (VRE)
in animal husbandry has been investigated
--------------------------------------------------------------------------------
Country Avoparcin
used VRE in
animal
husbandry Ref.
--------------------------------------------------------------------------------
Belgium + + 15
Denmark + + 13, 14
Finland + + 16
France + + 17
Germany + + 7
Great Britain + + 6
The Netherlands + + 18
Norway + + 19
Sweden – – 20
United States – – 21, 22
Transmission of VRE from Animals to Humans
Can an animal reservoir in itself be regarded a public health risk? What are the chances that VRE or the resistance genes will be transmitted from animals to humans? A public health risk must be assumed to exist when transfer from animals to humans can be shown directly or indirectly.
VRE are frequently present in food produced in Denmark as well as in food imported into Denmark from other European countries (23,24). Thus, exposure to humans from insufficiently heated food or cross-contaminated ready-to-eat food takes place. Unlike studies in the United States (21,25), European studies reported that humans frequently are fecal carriers of VRE (26-29). This suggests that VRE can be ingested from food in Europe. Furthermore, VRE was not detected in strict vegetarians in The Netherlands, supporting the view that the source of VRE is contaminated meat (Table 2) (28).
Molecular typing shows a very high diversity of VRE types in animals as well as humans (30). Nevertheless, similar or related types have been shown to occur in animals and humans on a number of occasions, supporting the assumption that transfer of VRE between humans and animals does take place (18,19). We have recently compared 84 isolates of E. faecium from swine, chickens, and humans in Denmark by SmaI generated macrorestriction profiles and EcoRI ribotyping. Similarity analysis by unweighted pair group method with arithmetic averages–derived dendrograms did not indicate a higher degree of similarity among E. faecium isolates (VRE as well as non-VRE) from humans than from animals. This finding indirectly supports the hypothesis that E. faecium from different food animals and humans are not discrete populations but belong to a common pool of E. faecium shared by animals and humans (data not shown).
Table 2. Prevalence of vancomycin-resistant
Enterococcus faecium in fecal samples of
residents in a vegetarian and nonvegetarian
nursing home, The Netherlands (28)
--------------------------------------------------------------------------------
No. persons
investigated No. E.
faecium
positive No. VRE
positivea,b
--------------------------------------------------------------------------------
Vegetarians 42 23 0
Nonvegetarians 62 32 6
--------------------------------------------------------------------------------
aP<0.05.
bAll VRE-positive samples were E. faecium.
The VanA gene cluster encoding for vancomycin resistance in animal and human VRE is located on a transposon designated Tn1546 (32,33). Tn1546 can easily spread from one enterococcal species to another as well as from enterococci to S. aureus (33,34). Recent investigations have documented that in vivo transfer of Tn1546 can take place in the mammalian intestinal tract (A. Sundsfjord, pers. comm.). Furthermore, animal VRE can colonize the human intestinal tract for at least 3 weeks after experimental ingestion of 107 CFUs of a single strain (35). This indicates that vancomycin resistance can spread in the gastrointestinal tract from transiently colonizing animal VRE to E. faecium strains of the resident human gut flora.
The VanA gene cluster consists of several genes. We investigated the genes and the regions between them by sequencing of selected areas, polymerase chain reaction amplification of other areas, and hybridization with specific probes (36,37). Thirteen different types were observed. Most differences arose from the presence of insertions or deletions in noncoding intergenic regions. One nucleotide difference was observed in the coding sequences; this point mutation occurred in the vanX gene at position 8234, where a G in the reference VRE strain was substituted for a T in some isolates.
In human VRE isolates, this mutation was evenly distributed, whereas in poultry isolates from different countries only the G variant occurred; in isolates from swine from different countries the T variant occurred in nearly all isolates (Table 3). Although we have no explanation for the uneven distribution of subtypes between different animals, the finding of both types in humans does support the hypothesis that animals are a primary source of vancomycin resistance genes in humans, whereas humans apparently do not serve as reservoir for animals, in which case both types would be expected to occur in both animal species. In the same investigation, we found that all human isolates from a Muslim country belonged to the poultry subtype (37). The absence of pork variant types in a Muslim country suggests that food of animal origin is a major reservoir for VRE in humans.
Table 3. Variations in Tn1546-
like elements of vancomycin-
resistant Enterococcus faecium
isolates of animal and human
origin (37)
--------------------------------------------------------------------------------
Source No.
isolates T
variant G
variant
--------------------------------------------------------------------------------
Humans 45 16 29
Pigs 33 32 1
Poultry 193 0 193
Total 271 48 223
--------------------------------------------------------------------------------
The European/American Paradox
Even though the greater frequency of VRE infections in U.S. than in European hospitals would seem to contradict it (12), the hypothesis that animals could serve as reservoirs of human VRE infections is supported by several lines of indirect evidence.
Heavy use of vancomycin (and probably also third-generation cephalosporins) is a prerequisite for frequent VRE infections in hospitals. Heavy use of vancomycin and third generation cephalosporins is more frequent in U.S. than in European hospitals (12,18). Thus, the problem in Europe, irrespective of a high carrier rate of VRE in the community, has not grown to the same proportions as in the United States. VRE infections in the United States are probably due to the heavy use of antibiotics in hospitals and the eventual spread of VRE within and among hospitals by carrier personnel (38).
Another prerequisite for high incidence of VRE hospital infections is a source of VRE. In the United States, primary sources of VRE to hospitals include travelers returning from abroad, tourists, and imported food. Once inside the hospital, VRE can cause nosocomial outbreaks because of its high potential to colonize and persist in the environment, which facilitates its persistence and spread (4). An alternative hypothesis could be that some clones of VRE have a higher potential to cause infections and that such clones are more prevalent in United States. This hypothesis, however, is contradicted by the high number of different types of VRE causing infections in Europe and the United States, which suggests that pathogenic potential is not limited to a few clones of VRE (38).
Avoparcin was approved for growth promotion in Europe in 1974. The first VRE was detected in a human patient in France in 1986. Does this suggest that VRE was not present in animals before 1986? Historically, resistance to growth promoters in animal bacteria was not monitored, and with few exceptions the studies conducted have looked at bacteria other than enterococci because enterococci were not considered foodborne pathogens. Thus, if VRE were not detected in food animals, it may be because they were not looked for.
The Effect of Prohibiting Use of Avoparcin as a Growth Promoter
Because of public health concerns about resistance to glycopeptide antibiotic drugs, avoparcin was banned in Denmark in 1995. In 1996, Germany took a similar step, and finally in 1997, avoparcin was banned in all EU member states. After the ban in Denmark, a marked reduction in the occurrence of VRE in Danish poultry flocks has been observed at slaughter (from 82% in 1995 to 12% of flocks in 1998; x2 = 68.3 on 5 df.; p <0.0001), whereas in swine only a minor reduction has been observed (Figure) (39). In Germany, a decrease in the incidence of VRE in poultry meat and in fecal samples from humans in the community was observed after discontinuation of avoparcin use in animal husbandry (40). In poultry meat the proportion of VRE-positive samples were reduced from 100% in 1994 to 25% in 1997, and in fecal samples from humans in the community, the carrier rate decreased from 12% in 1994 to 3% in 1997.
Figure. Trend in the proportion of Enterococcus faecium isolates
resistant to vancomycin (VRE) during successive half-year periods
from second half of 1995 to first half of 1998 (39).
Similar Problems Related to Other Antimicrobial Growth Promoters
Most of the different growth promoters approved in the EU are active against gram-positive bacteria. With increasing resistance in gram-positive pathogenic bacteria, antimicrobial drugs used as growth promoters have attracted renewed attention as potentially useful for human therapy. More than 10 years after the first VRE was discovered, the first drug for humans with good clinical effect against VRE infections is ready to be marketed. This drug is a combination of two streptogramins, quinupristin and dalfopristin (Synercid).
For decades, virginiamycin, which belongs to the group of streptogramins, has been used as a growth promoter in the European Union as well as in the United States, primarily for poultry production. Investigations in the United States, The Netherlands, and Denmark have frequently found Synercid-resistant E. faecium in poultry (41-43). As for VRE, we have no data on the prevalence of streptogramin-resistant E. faecium in animal husbandry before virginiamycin was used as a growth promoter. No monitoring has been carried out. Moreover, the gene (satA) conferring resistance to virginiamycin and Synercid have been found in animals and humans (44), and in vivo transfer of these genes from resistant to sensitive strains of E. faecium in the mammalian gastrointestinal tract has been shown (45). Thus, the events associated with avoparcin and vancomycin may be recurring for Synercid and virginiamycin. Furthermore, the drug anticipated to be next in line after Synercid, a compound called Ziracin, belonging to the class of everninomicins, is practically identical to another growth promoter called avilamycin, which has primarily been used in poultry.
We have detected avilamycin resistance in 69% of E. faecium isolates from poultry in Denmark (43). Moreover, preliminary investigations show that resistance to avilamycin gives cross-resistance to Ziracin and that a transferable genetic element may be involved (46). Thus, again use of an antimicrobial drug as a growth promoter may have created a major animal reservoir of resistant E. faecium, threatening to shorten the life span of a new promising drug when it is put to use in humans.
Future Perspectives
At the core of the VRE issue appears to be the way antimicrobial drugs are being developed. New classes of antimicrobial drugs are not available. Instead, old drugs are being modified that may have been used in agriculture as growth promoters for decades because they were not considered useful for humans. Now that physicians are searching for more options in antibiotic treatment, the older drugs may no longer be viable. The use of antimicrobial drugs and development of resistance in animals and humans are interrelated. Therefore, systems to monitor antimicrobial resistance in pathogenic and commensal bacteria should be established. Such systems should cover relevant bacteria from the entire farm-to-fork chain and monitor resistance towards antimicrobial drugs used in both animals and humans, including growth promoters (47-49).
Finally, antimicrobial agents should not be used for growth promotion if they are used in human therapeutics or are known to select for cross-resistance to antimicrobial drugs used in human medicine (47). Antimicrobial agents are too valuable to be used as a tool in animal production because any antimicrobial drug may be useful for human therapy in the future even if not used therapeutically today. Adherence to the World Health Organization recommendations (47) will ensure a systematic approach toward replacing antimicrobial growth promoters with safer nonantimicrobial drug alternatives. The EU countries entered this process in December 1998 when four growth promoters (tylosin, spiramycin, bacitracin, and virginiamycin) were banned because of their structural relatedness to therapeutic antimicrobial drugs used for humans (50).
--------------------------------------------------------------------------------
Dr. Wegener is head of The Danish Zoonosis Centre. His research interests are veterinary public health, microbiology, epidemiology, molecular biology; control of zoonoses, particularly the so-called "modern" bacterial zoonoses; and potential public health consequences of the use of antimicrobial drugs in animal husbandry.
Address for correspondence: Henrik C. Wegener, Danish Zoonosis Centre, Danish Veterinary Laboratory, Bülowsvej 27, DK-1790 Copenhagen V, Denmark; fax: +45-35-300-120; e-mail: [email protected].
References
Edmond MB, Ober JF, Weinbaum DL, Pfaller MA, Hwang T, Sanford MD, et al. Vancomycin-resistant Enterococcus faecium bacteremia: risk factors for infection. Clin Infect Dis 1995;20:1126-33.
Leclerq R, Derlot E, Duval J, Courvalin P. Plasmid mediated resistance to vancomycin and teicoplanin in Enterococccus faecium. N Engl J Med 1988;319:157-61.
Centers for Disease Control and Prevention. Summary of Notifiable Diseases—United States, 1997. MMWR Morb Mortal Wkly Rep 1998;46:1-87.
Centers for Disease Control and Prevention. Recommendations for preventing the spread of vancomycin resistance. Recommendations of the Hospital Infection Control Practices Advisory Committee (HICPAC). MMWR Morb Mortal Wkly Rep 1995;44:RR12.
House of Lords Select Committee on Science and Technology: Resistance to antibiotics and other antimicrobial agents. 1998. London: The Stationary Office; 1998.
Bates J, Jordens J, Griffith DT. Farm animals as a putative reservoir for vancomycin resistant enterococcal infections in man. J Antimicrob Chemother 1994;34:507-16.
Klare I, Heier H, Claus H, Reissbrodt R, Witte W. VanA-mediated high-level glycopeptide resistance in Enterococcus faecium from animal husbandry. FEMS Microbiol Lett 1995;125:165-72.
Jensen BB. The impact of feed additives on the microbial ecology of young pigs. Journal of Animal and Feed Sciences 1998;7:45-64.
McDonald CL, Kuehnert MJ, Tenover FC, Jarvis WR. Vancomycin-resistant enterococci outside the health care setting: prevalence, sources, and public health. Emerg Infect Dis 1997;3:311-7.
Wegener HC. Historical usage of glycopeptides for animals and humans—the American/European paradox revisited. Antimicrob Agents Chemother 1998;42:3049.
Witte W. Medical consequences of antibiotic use in agriculture. Science 1998;279:996-7.
Kirst HA, Thompson DG, Nicas TI. Historical yearly usage of vancomycin [letter]. Antimicrob Agents Chemother 1998;42:1303-4.
Aarestrup FM. Occurrence of glycopeptide resistance among Enterococcus faecium isolates from ecological and conventional poultry farms. Microb Drug Resist 1995;1:255-7.
Bager F, Madsen M, Christensen J, Aarestrup FM. Avoparcin used as a growth promoter is associated with the occurrence of vancomycin-resistant Enterococcus faecium on Danish poultry and pig farms. Prev Vet Med 1997;31:95-112.
Devriese LA, Ieven M, Goosens H, Vandamme P, Pot B, Hommez J, et al. Presence of vancomycin-resistant enterococci in farm and pet animals. Antimicrob Agents Chemother 1996;40:2285-7.
Tast E, Myllys V, Honkanen-Buzalski T. A survey of resistance to some antimicrobials of enterococcal and E. coli strains isolated from pigs and broilers in Finland. In: Proceedings of NKVet Symposium on Antibiotic Resistance. 1997 Nov 7-8. Danish Veterinary Association, Sundvolden, Norway. p. 44.
Boisivon A, Vauchel JC, Cheron M, Gobert A, Leturdu F, Chambreuil G, et al. Vancomycin resistant enterococci (VRE) from food animal sources in France. In: Proceedings of the 97th General Meeting of the American Society of Microbiology; 1997 May 4-8; Miami Beach, Florida. Washington: American Society of Microbiology; 1997.
van den Bogaard AE, Jensen LB, Stobberingh EE. Vancomycin-resistant enterococci in turkeys and farmers. N Engl J Med 1997a;337:1558-9.
Simonsen GS, Haaheim H, Kruse H, Dahl KH, Olsvik Ø, Sundsfjord A. Glycopeptide resistant Enterococci (GRE) at avoparcin-using farms: possible transmission of strains and the vanA gene cluster between chicken and humans. In: Proceedings of NKVet Symposium on Antibiotic Resistance. 1997 Nov 7-8. Danish Veterinary Association, Sundvolden, Norway. p. 41.
Quednau M, Ahrné S, Molin G. Antibiotic resistant enterococci in Swedish and Danish pork and poultry. In: Proceedings of Symposium on Food Associated Pathogens; 1996 May 6-8; The Swedish University of Agricultural Sciences, The Swedish National Committee of Food Science and Technology, and the International Union of Food Science and Technology, Uppsala, S
in press). 
