Dairy Cattle Antibiotic Residue Review

What’s in our food?
The seemingly ever increasing number and volume of meat recalls has made consumers aware of the risks of food borne illnesses that may be transmitted via contaminated meat. Between 2004 and 2009 466 million pounds of meat were recalled. This includes the staggering 143 million pounds in the single recall of February 2008 from the Hallmark/Westland Meat Packing Co. Fifty seven percent of all meat recalled was beef and the major reasons for recall were Listeria and E. Coli contamination.

The onus to avoid potential risks from contaminated meat has been moved from the meat industry to the consumer. Consumers are becoming used to advice to avoid potential infection from tainted meat by cooking it thoroughly and using a meat thermometer to make sure it reaches an internal temperature of at least 160 degrees—sound  advice if there is a chance of  acid resistant E. Coli from feedlot production. However, far fewer consumers are aware of the scale of a different contamination and one that cannot be mitigated by good hygiene or cooking practice. The issue in question is antibiotic residue in meat and it appears that the dairy sector is the biggest offender.

Dairy beef
When you think of beef, dairy cattle don’t readily spring to mind.  Dairy animals provide milk and don’t contribute to overall meat production and consumption. However; of the 33.3 million head of animals slaughtered for beef production in 2009, 2.8 million were dairy cows. In other words 8.6% of all the animals slaughtered to produce beef were actually culled dairy cows. In addition, 944 thousand veal calves were slaughtered in 2009. This is a sizeable amount of meat coming from the dairy sector both directly and indirectly.

Aside from the volume of meat produced by the dairy sector it is worth noting the destination of much of this product. One of the reasons the Hallmark/Westland Meat Packing Co. recall was so shocking was not just the volume of the recall but the fact that much of the meat was destined for the National School Lunch Program.  Most of the cows shown on the undercover videos that lead to the temporary closure of the plant were clearly culled dairy cows. A dairy cow has not been bred to produce prime steaks and other cuts of meat and the vast majority of meat from such cows ends up as ground beef.  Some of this is the source for hamburgers in fast food restaurants, but a lot will go into schools. You might assume that a product destined to feed children would undergo significant monitoring and testing; be at risk of statutory recall procedures in case of problem and maybe even have additional safeguards. However, according to a recent report by the Office of the Inspector General (OIG) it seems this may not be the case.

The OIG report
The recent OIG report on the FSIS National Residue Program for Cattle is not encouraging. This report states that the National Residue Program is not accomplishing its mission of monitoring the food supply for harmful residues. In addition the report notes that even when residue testing is carried out FSIS does not attempt to recall meat, even when its tests have confirmed the excessive presence of veterinary drugs.

The OIG report also makes the point that plants handling dairy cows and veal calves are responsible for 90% of all drug violations found. The dairy sector is therefore the most significant when it comes to this important issue.

The report goes on to say that “The three agencies responsible for the national residue program—FSIS, FDA, and EPA—have not effectively coordinated their various roles so that they can ensure that harmful residue is not entering the U.S. food supply.”

Allergies
A U.S. Justice Department complaint has recently been filed for permanent injunction against Scenic View Dairy of Hamilton, Michigan, alleging that the company sold dairy cows for human consumption that contained illegal drug residues in edible tissues. A news report on this particular case quoted Arthur Currey, veterinarian and instructor of food animal medicine and surgery at Michigan State University as saying it was unlikely the antibiotics used to treat the animals would harm humans – and that the only people who would be affected are those who have an allergy to that antibiotic. He went on to say that such an allergy was extremely rare.

In fact, an allergy to antibiotics is more common than might at first be thought. Penicillin-type antibiotics are the most common cause of allergic drug reactions and epidemiologic studies place the prevalence of penicillin allergy at between 1% and 10% of the general population. At the 1% level this is around 3.1 million people in the U.S.; at the 10% level, 31 million people. Not all of these potentially allergic people will show life threatening reactions to antibiotics, but some of them will.

Resistance
Aside from potential allergic reactions there are other reasons why action must be taken to ensure meat is free from antibiotic residues. The most important of these is the growing problem of antibiotic resistance. The U.S. Food and Drug Administration state that almost all bacteria implicated in serious bacterial infections in the United States and throughout the world are becoming resistant to antibiotics. Antibiotic resistance has been called one of the world’s most pressing public health problems.  Misuse of antibiotics such as unnecessary sub-therapeutic use, under-dosing (not giving the prescribed amount or cutting the number of doses back), and off-label use could all potentially contribute to an increase in antibiotic resistance.

Testing
The Food Safety and Inspection Service (FSIS), the U.S. Department of Agriculture’s public health regulatory agency, works with the Environmental Protection Agency (EPA) and the Department of Health and Human Services’ Food and Drug Administration (FDA) to control veterinary drug, pesticide, and environmental contaminant residues in meat, poultry, and egg products. Every year FSIS publishes the ‘Red Book’ which explains FSIS’ chemical residue sampling plans and presents National Residue Program (NRP) testing results by calendar year.  The most recent edition presents results from 2008.

There are two different types of testing – scheduled sampling and inspector generated sampling. Scheduled sampling plans consist of the random sampling of tissue from healthy appearing food animals. The total number of scheduled samples that must be taken for each class of animal each year is set by FSIS. For example the 2009 FSIS National Residue Program Scheduled Sampling Plans suggests that 300 dairy cows be tested for antibiotics and 300 dairy cows tested for presence of the anti-inflammatory drug flunixin and so on.

Inspector generated sampling targets individual suspect animals and suspect populations of animals. Animals are selected based on the inspector’s professional judgment and on criteria outlines by FSIS. The criteria include factors such as signs of disease and producer history. When an inspector generated sample is collected, the carcass is held pending the results of laboratory testing. If a carcass is found to contain levels of residues above those held to be acceptable, the carcass should be condemned.

Dairy cow results from 2008
In 2008, scheduled inspections for dairy cows included only 1,099 of the 2.7 million dairy cows slaughtered for meat in total – less than half a percent. Perhaps unsurprisingly, no residues that breached FDA requirements were found.

In 2008, inspector generated sampling covered 80,131 dairy cows – fewer than 3% of all dairy cows slaughtered for meat. Of these, 788 cows had violations across a wide range of drugs, as shown below. Note that some cows tested positive for more than one compound so the list of drug violations shown below totals more than 788.

Amikacin    1
Ampicillin  8
Ceftiofur   69
Dihydrostreptimycin   3
Flunixin   269
Gentamicin   57
Neomycin  25
Oxytetracyclin    46
Penicillin   350
Phenylbutazone    3
Sulfadimethozine  193
Sulfamethozine   34
Tetracycline    21
Tilmycosin   6
Tylosin 1

Veal calf results for 2008
There is a similar story for veal. Only 818 samples were taken under scheduled sampling in 2008 from a slaughter total of roughly 900,000 animals. Even in this small sample, two violations were found. An examination of inspector generated sampling reveals that a fast Antimicrobial Screen Test was used to screen 32,890 “bob” veal calves – those calves slaughtered very young for veal –  for antibiotics and sulfonamides. Of the animals tested, FSIS laboratory confirmed 406 violations in 292 animals. The residue violations consisted of:

Desfuroylceftiofur DCA or DCCD    19
Gentamycin Sulfate      39
Neomycin   178
Oxytetracycline   12
Tetracycline     7
Tilmicosin    6
Penicillin    34
Sulfadiazine   4
Sulfadimethoxine   9
Sulfamethazine   27
Sulfamethoxazole  28
Sulfathiazole   1
Flunixin   42

Having found these drugs within the samples tested what happens next? In theory any carcass that tests positive for drug residues should be destroyed. However the recent OIG report mentioned above found that there were instances where plants had released meat from carcasses that tested positive for drug residues into the food supply. Although the drugs involved could result in stomach, nerve, or skin problems for consumers, the report says that FSIS requested no recall. In addition the same report points out that FSIS is inadequately testing for many drugs – the figures presented above would seem to support this – and fails entirely to test for other drugs.

What are the drugs?
So what are all these drugs and why are they present? Drugs that are being found in the small number of samples tested each year include antibiotics like penicillin, florfenicol, sulfamethazine and sulfadimethoxine, the anti-parasite drug ivermectin and the non-steroidal anti-inflammatory drug flunixin.  For veal calves the most commonly found drug is the antibiotic neomycin.

For dairy cows the most common reason for treatment with antibiotics is mastitis. Mastitis is a condition that results in painful inflammation of the cow’s udder. Unfortunately one of the most common reasons for culling dairy cows is unresolved mastitis. The most common drug used for mastitis treatment is penicillin but sulfamethazine and other sulfa drugs are also being found. One major problem with these latter drugs is the fact that they are not licensed for use in any dairy animal over 20 months. They are not supposed to be used in lactating dairy cows at all. However, these drugs are turning up in older cull cows following “off label” use.
The lists above show other drugs that simply should not be present. Phenylbutazone is known to induce blood disorders in humans, including aplastic anemia,leukopenia, agranulocytosis, and thrombocytopenia. Therefore, in 2003 the FDA-CVM instituted a ban on the use of phenylbutazone in dairy cattle and there is a zero tolerance policy for residues yet it was found within the relatively small sample size used for testing in 2008.

Why is phenylbutazone used? The product is a Non-Steriodal Anti-Inflammatory (NSAID), as is flunixin – another product which shows up in a large proportion of cows that test positive. NSAIDs can be used in cases of mastitis and for uterine infections following calving (metritis). They can also be used to alleviate pain in a lame animal. From the statistics presented here we can only speculate on the reason these NSAIDs are turning up on such a regular basis. However, it is worth noting that a cow that is so lame she cannot walk has no value – she must be euthanized where she lies. A cow that has been given pain medication and can therefore walk onto the truck and be taken to the slaughter plant has a value.

Off label use
Flunixin is also a good example of a product that is commonly used “off-label”. The term “off-label” is used whenever a drug is used in a way other that which it is licensed for. “Off label” use might include giving the drug to a species that it isn’t licensed for; using a drug for a disease or health problem that it isn’t specifically licensed for; using a drug at different dosage than it is licensed for or giving the drug by a different method than it is licensed for. This latter is common for flunixin. The drug is licensed for intravenous use only – something that is normally only attempted by veterinary surgeons because of the risk of harming the cow if the injection goes wrong. Because of the risk of intravenous use, many farmers deliver the drug via the simpler intramuscular route. However, it has been shown that if the drug is given intramuscularly it has a longer withdrawal time than if it is given intravenously. This “off label” use, therefore, is increasing the potential for residue.

Veal
It is a similar story with veal. The antibiotic neomycin is the most common drug found in veal calves. Where does it come from? Most of these residues will come from medicated milk replacer: neomycin and oxytetracycline are commonly found in combination in medicated milk replacer. However, this medication is not licensed for feeding veal calves – precisely because of the potential for antibiotic residues.

If the issue of resistance is also brought to bear, neomycin is problematic on that front too. The ratio of neomycin to oxytetracycline in milk replacer has recently been adjusted partly in response to the effect on E. coli bacteria. In 2004, the American Society of Animal Science published a study titled, “Effect of Antibiotics in Milk Replacer on Fecal Shedding of E. Coli O157:H7 in Calves.” The study was conducted at Kansas State University. In part, the study states, “Supplementation of milk replacers with antibiotics may increase the probability of E. coli O157:H7 shedding in dairy calves”. Aside from this point it is worth noting that neomycin is a drug that is used in human medicine – particularly for patients undergoing gut surgery. This is therefore not a drug for which we want to encourage any kind of build-up of resistance.

Gentamicin is also a fairly common finding for those veal calves testing positive for residues. E. coli bacteria have already shown some resistance to gentamicin, which is a heat-stable antibiotic. The U.S. Food and Drug Administration has not established any tolerance level for gentamicin in the edible tissues of veal calves. As with neomycin, this drug should not be present at all in veal calves.

Another issue for bob veal calves is that they may be fed waste milk from the dairy. Waste milk is milk that cannot be sold directly for human consumption – quite often because it comes from cows being treated for mastitis and other health problems. Any antibiotic administered to the cow will appear as a residue in the milk. If this milk is then fed to calves they will have antibiotics in their system and, if slaughtered for meat without any withdrawal time, will have residues of the drug in their meat. If the calf is able to suckle its mother – rare in the intensive dairy sector – it may also pick up antibiotics as the remnant of antibiotic dry cow therapy given to the mother to treat or prevent mastitis.

Veterinary oversight
So what is happening on these farms? Is there no oversight of veterinary treatment? A survey carried out between 2001 and 2002 found that only 50% of the dairy herds surveyed maintained records of antibiotic treatments. Only 21% of dairies had health plans or protocols for treating sick animals and only 24% of dairy producers said that they always completed the course of antibiotic treatment. Not all farms checked with a veterinarian before using antibiotics “off-label” i.e. when the drug is given in a different way, a different amount or to a different animal than that which it is licensed for. As an example, 18% of all farms surveyed were using the drug ceftiofur “off-label.” Seventy percent of the farms fed medicated milk replacer to their calves usually containing the antibiotics oxytetracycline and neomycin.

The published study based on this survey (Sawant et al 2005) concluded that antibiotics are used extensively on dairy herds for both therapeutic and prophylactic (preventative) purposes and anticipated that the findings of the survey would help to develop new strategies for the “prudent” use of antibiotics on dairy herds. Sadly the figures presented above indicate that there has not been much improvement on the situation.

Withdrawal times
To add to the problems outlined above, some studies have shown that even if the stated withdrawal time is adhered to it may not be enough to prevent residues. Rogers et al (2004) found that thirty-one percent of cows treated with penicillin G procaine still had the drug in their system after the required 10 day label withdrawal recommendation. On average cows were not clear of detectable penicillin until 3.1 days after the end of the official 10 day withdrawal.  Some cows still showed traces of penicillin up to eight days after the end of the official withdrawal period. The report speculated that unhealthy cows would have reduced feed intake and water and that furthermore, metabolism is probably decreased in unhealthy cows thus extending the time that it takes for the drug to be broken down in the body.

The issue of withdrawal times is confused further by the fact that the same drug may have different withdrawal times for milk and for meat. Some penicillin compounds have a milk withdrawal of 72 hours but a meat withdrawal of 10 days. The dairy herdsman at least initially may well be treating the cow as a milking animal and will work to the 72 hour withdrawal. If the cow shows no signs of recovery and is then culled as soon as possible in order to get some economic return from her the fact that she now needs to go through an additional seven day withdrawal for meat may not be recognized.

What happens when residues are found?
It seems clear from the points raised above that only a small proportion of all animals from dairy herds – whether cows or calves – are being tested for drug residues, and residues are being found in a proportion of this small sample size. We have noted that the OIG report states that the response of FSIS is inadequate when residues are found.

Earlier we also noted the case of the dairy in Michigan that has recently had a complaint filed against it. This sounds like action is being taken until it is noted that this dairy has a history of drug residue violations dating back to 2003.

The FDA does issue warning letters to farms that are found to have drug residues in meat. During 2008 FDA issued over 30 warning letters to dairies and farms that offered for sale animals as food that contained approved and unapproved drug residues in residual tissues in excess of FDA tolerance levels. It was noted that the FDA found that the animals were held under conditions that were inadequate to prevent medicated animals bearing potentially harmful drug residues from entering the food supply. Many of the drugs were not used in conformance with the approved labeling. Twenty nine of these letters were to dairies or veal operations and the remaining letter was to a beef operation.

For 2009, 37 warning letters were issued.  Nearly all these letters state:

“Our investigation also found that you hold animals under conditions that are so inadequate that medicated animals bearing potentially harmful drug residues are likely to enter the food supply. For example, you failed to maintain complete treatment records that include the dosage amount, route of administration, and the withholding period for drugs administered to the cattle to ensure that treated cattle are not culled before labeled meat and milk withhold times are met. Food from animals held under such conditions is adulterated within the meaning of section 402(a)(4) of the Act [21 U.S.C. § 342(a)(4)).”

The majority of the warning letters in 2009 were again issued to dairies – there were three calf raising/veal operations, two cattle operations, and the rest dairy.

In 2010 there have been 30 letters issued to date – so it looks likely that the number of letters will increase from 2008 to 2009 and to 2010.

Multiple violations
It might be thought that only 30+ incidences that required warning letters is not something that should really concern us. At this point we have to refer to the FSIS residue violator lists. These lists are published weekly and show not only the plants where animals have been found with positive drug residue samples – and the farms that consigned these animals – but also list those farms that have been repeat offenders in the previous 12 months. The weekly lists amount to around 150 pages.  One plant on the latest week’s list has nine violations alone – another has eight for the same week. The list of violators over the last 12 months runs into hundreds of farms –not that surprising when the residue testing results presented above are examined.

The OIG report points out that in 2008, individual plants amassed as many as 211 violations. It goes on to says that FSIS has had a longstanding problem of not being able to identify the producers of cattle that have tested positive for residue, as dairy cows often pass through several buyers and sellers before they are presented for slaughter by suppliers. Without this information, FSIS will always be limited in its ability to respond to repeat violators and to prevent such cattle from entering the slaughter plants. The FSIS residue violator lists for 2010 suggest that this issue has yet to be resolved with many plants and farms racking up multiple violations.

Reducing antibiotic use
As noted above mastitis is the most common dairy cow health problem that will require treatment with antibiotics.  And from the points above it would appear that residues may potentially arise when dairy cows are given a drug that isn’t actually licensed for milk cows, when they are given a drug that is permitted but are not given enough withdrawal time and when they go through the “official” withdrawal time but for various reasons the drug is still in their system. It is clear that there needs to be a better system for monitoring and testing meat from the dairy sector but there are other steps that can be taken to minimize residues and those steps must include reducing the overall level of antibiotic that needs to be administered. In other words if we improve cow health – and specifically if we reduce mastitis – we don’t need to use as many antibiotics in the first place.

Pasture vs. intensive
There are numerous articles and papers on the control and prevention of mastitis. There are two main types of mastitis; contagious mastitis from bacteria that live on the skin and environmental mastitis which as the name suggests comes from bacteria found in the cows’ environment. Good hygiene is paramount in helping to prevent mastitis. To prevent environmental mastitis experts advise keeping the cows in clean surroundings. Not surprisingly many specifically recommend managing cows on clean pasture and all indicate that dirty pens or stalls, muddy pastures and dirt lots carry the greatest risk of environmental mastitis. One example comes from the Virginia Extension Service (see references) which published a fact sheet stating that many mastitis infections originate in the time around calving. Their recommendation is that the calving area should be a well-drained clover-grass pasture with no access to ponds or swampy areas. They go on to state that filthy, damp, or muddy pens, lots, or pastures continually expose the teat end to a barrage of bacteria and so promote mastitis. A similar paper from UC Davis also mentions the benefits of clean pasture particularly when this is rotated regularly.

Unfortunately despite all this advice many dairies keep their cows indoors all the time or only provide limited access to dirt lots. Even those dairies that allow some pasture access often use the same small area continually, denuding the area of grass, building up manure contamination and increasing the risk of bacterial build up. Animal Welfare Approved (AWA) standards require that all animals have access to well managed pasture – not just so that cows can graze and have access to fresh air and sunshine but so that the risk of any illness including environmental mastitis is reduced. If more dairies managed their cows in pasture based systems their animals could be healthier and there would be less need to use antibiotics and less risk of residue.

Where do we go from here?
As stated at the beginning of this report it would appear that there is a serious problem with drug residues in meat that originates from the dairy industry. These residues are problematic for two main reasons. Firstly, some consumers are allergic to some of the drugs that may be present and could suffer life-threatening reactions if they consume meat with, for example, penicillin residue. Secondly, antibiotic residues in meat is indicative of their misuse which can lead to the development of strains of bacteria that are resistant to antibiotics—thus potentially having an effect on human health through the reduction in efficacy of our antibiotic armory.

The problem is further compounded by the fact that antibiotic residues do not diminish with cooking the meat.  In fact the OIG report states that cooking may break these drugs down into even more harmful compounds. In addition – if any more reason to take this issue seriously was needed – meat from the dairy sector is not prime beef; it tends to be turned into ground beef and a large proportion is destined for school food, to the potential detriment of the health of our children.

AWA believes that the testing regime for drug residues is wholly inadequate. Furthermore there appears to be an inability to clamp down on those who repeatedly consign meat with residues for slaughter and sale and a failure to ensure such meat with residues is either not released or is recalled from sale. This is demonstrated by the number of repeat offenders and the lack of recalls of meat on this specific issue. The fact that some of the more commonly found drugs are not even licensed for lactating dairy cows shows the extent of the problem and the need for greater awareness and education within the sector.

References

Sawant AA, Sordillo LM, Jayarao BM. J Dairy Sci. 2005 Aug;88(8):2991-9.A survey on antibiotic usage in dairy herds in Pennsylvania.

Rogers et Al 2004

Slaughter statistics
http://usda.mannlib.cornell.edu/usda/current/LiveSlauSu/LiveSlauSu-04-29-2010.pdf

OIG report on the FSIS National Residue Program for Cattle
http://www.usda.gov/oig/webdocs/24601-08-KC.pdf

Information on Scenic View Dairy
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm224574.htm

Prevalence of penicillin allergies
Lin RY. A perspective on penicillin allergy. Arch Intern Med.1992; 152:930-7]

Antibiotic resistance
http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/AntibioticsandAntibioticResistance/default.htm

National Residue Program (NRP) testing results
http://www.fsis.usda.gov/PDF/2008_Red_Book.pdf

FSIS National Residue Program Scheduled Sampling Plans
http://www.fsis.usda.gov/PDF/2009_Blue_Book.pdf

FDA enforcement letters
http://www.fda.gov/downloads/ICECI/EnforcementActions/EnforcementStory/UCM129816.pdf

FSIS residue violator list
http://www.fsis.usda.gov/PDF/Residue_091610.pdf

Antibiotic residues in veal calves
http://www.calfnotes.com/pdffiles/CN106.pdf

Mastitis prevention
http://pubs.ext.vt.edu/404/404-229/404-229.html
http://www.uwex.edu/milkquality/PDF/coliform_mastitis.pdf
http://pubs.ext.vt.edu/404/404-233/404-233.html
http://animsci.agrenv.mcgill.ca/courses/450/topics/13.pdf
http://www.vetmed.ucdavis.edu/vetext/INF-DA/INF-DA_MastitisControl/environmental_strep.pdf