Antibiotic Residues

DEPARTMENT OF DAIRY SCIENCE MADRAS VETERINARY COLLEGE CHENNAI-07 VPH-311 ASSIGNMENT ON:

ANTIBIOTIC RESIDUES IN MILK

SUBMITTED TO: Dr.S.GNANALAKSHMI Ph.D, ASSISTANT PROFESSOR DEPARTMENT OF DAIRY SCIENCE

SUBMITTED BY: BOON ALLWIN BVM-06024-A BATCH III-B.V.Sc & A.H

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ANTIBIOTIC RESIDUES IN MILK Introduction The presence of drug or antibiotic residues in milk and meat is illegal. Milk supplies containing detectable concentrations are not acceptable. Unless drug residues are avoided to protect milk's reputation as a healthy, safe food, the market becomes jeopardized. Consumers want to be confident that their food supply is free of contamination by herbicides, pesticides, drugs, or antibiotics. Approximately 5-10 percent of the population is hypersensitive to penicillin or other antibiotics and suffers allergic reactions (skin rashes, hives, asthma, anaphylactic shock) at concentrations as low as 1 ppb penicillin. There is concern that small amounts of certain antimicrobial agents may significantly shift the resistance patterns in the microbial population in the human intestinal tract. Antibiotics are known to interfere with the manufacture of several dairy products. Concentrations of 1 ppb delay starter activity for cheese, butter, and yogurt. Antibiotics also decrease the acid and flavor production associated with butter manufacture, and they reduce the curdling of milk and cause improper ripening of cheeses.

. To protect consumers’ health: Antibiotics entering the food chain may lead to allergic reactions in humans and antibiotic resistant strains of bacteria. To safeguard : It is essential that the dairy industry as a whole produces high quality milk which is free from antibiotic residues. To avoid heavy penalties for producers: In future, losses incurred by processors having to discard milk may be passed back to the producer. 2

To prevent losses to processors: Production of cultured dairy products can be adversely affected by traces of antibiotics, resulting in sub-standard product. Specifications for valuable home and export markets require dairy products to be free from antibiotics. To comply with current legislation: Contamination of milk is an offence liable to prosecution.,to ensure that food producers and handlers are not convicted of an offence which they took all reasonable care to avoid. It is therefore important that all milk producers are able to show that they have taken all reasonable precautions to ensure the safety of milk being sold by them.

Antibiotic residues in milk may lead to: severe allergic reactions in sensitive consumers,culture failure and subsequent loss of product,a change in consumer perception of milk being a pure, unadulterated, natural product. All of these concerns may result in major economic losses to the dairy industry.

SOURCE OF DRUG RESIDUES Drugs are administered to dairy cows for treatment of mastitis through intramammary or intravenous infusions and for disease therapy by intramuscular or intravenous injections, oral administration, feed supplementation, or reproductive infusions. FDA surveys indicate that improper use of drugs in the control of mastitis is the major source of residues found in the milk supply. The beef industry claims that a great percentage of the drug residues found in beef carcasses are in those of culled dairy cows.

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Many drugs are retained in the animal body for longer times than indicated by label discard times. Consequently, milk samples remain positive for residues. A good example is penicillin with a recommended milk discard time of 72 hours. However, penicillin residue has persisted in milk for as long as 18 days. Other drugs may cause residues. At the end of the label withholding time, we have detected drug residues in 35% of cows treated with cephapirin for mastitis and 27% of cows given intramuscular injections with penicillin (Table 1). Some of the cephapirin treated cows were still positive at 48 hours after the recommended milk discard time. Drugs administered for dry cow therapy do not appear to cause drug residues if milk is not shipped for the first four days after calving, if dry periods are l's recommendations are followed, dry cow therapy should not result in residues after calving. However, residues are possible and fresh cows should be tested, especially cows with short dry periods.

Discard Time

Cephapirin Penicillin --% Cows Cleared - Recommended 65 7 - - - % Cows + - - ---+ 1 day 35 27 + 2 days 21 20 + 3 days 12 13 Number of cows 34 15 Route of administration Intramammary Intramuscular Intrauterine infusions of drugs have caused detectable residues in milk. Studies have reported residues caused by intrauterine treatment with tetracycline, dihydrostreptomycin, benzyl penicillin, oxytetracycline, sulfamethazine, and penicillin streptomycin. Combiotic (procaine penicillin and dihydrostreptomycin) has been detected in milk for 24-48 hours after intrauterine infusion.

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Suspected reasons for drug residues include: • • • • • • • • • • • • • •

Extended usage or excessive dosage of approved drugs. Poor records of treatment. Milker or producer mistakes“accidental transfer into bulk tank. Failure to observe recommended label withdrawal time. Lack of advice on withdrawal period. Prolonged drug clearance. Treated-animal identification problems. Multiple dosing. Products not used according to label directions. Withholding milk from treated quarters only. Contaminated milking equipment. Early calving or short dry periods. Purchase of treated cows. Use of dry cow therapy to lactating cows.

RECOMMENDED USE OF ON-FARM DRUG RESIDUE TESTING Certain situations have greater risks for residues. Withholding times on the label may have been established with healthy or high producing cows where the drug retention is less than occurs in sick or diseased cows. Consider using a drug residue screening test as follows: 1. Fresh cows, especially those dry treated and with dry periods of six weeks or less, cows that freshen early, cows which had been treated shortly before calving, or cows whose treatment status was unknown. Discard milk for the first three days after calving. This includes first lactation cows who had been treated with either a lactating or dry cow mastitis treatment prior to calving. Also, test cows that received intrauterine drug infusions.

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2. At the end of the recommended milk discard time and after the milk becomes visually normal, test milk from any lactating cow treated for mastitis. 3. At the end of the veterinarian's recommended withholding time, which should be stated on the drug label, test any cows treated "extra-label." Also, test problem cows that have been treated longer than recommended, or with higher doses, or with combinations of drugs or special mixes. 4. All new additions to the herd including purchased cows or first lactation animals should be tested before their milk is added to the bulk tank. 5. Any cull cows that have been treated or baby calves that have been fed milk from treated cows should not be sold until the end of the withdrawal time for meat animals. Calves born to cows treated during the dry period may acquire tissue drug residues prior to birth or from drinking colostrum.. Certain factors increase the reliability of using antibiotic residue screening tests. These include: • • • • • • •

• • • • •

Choose a screening test that is appropriate for detecting the antibiotic administered. Do not treat cows who have little chance to respond, e.g., for example, cows chronically infected with Staphylococcus aureus. Test milk that is visually normal. Test composite milk rather than foremilk. If test result is negative, milk is acceptable to add to bulk tank. If test result is positive, continue to withhold milk from bulk tank and retest cow in 24 hr. Without screening individual cows, a dairy farm risks adding positive milk to the bulk tank. With screening individual cows, a dairy farm risks disposal of milk that might be antibiotic free All cows should be given an identity Use freezing branding, large ear tags or similar. Clearly mark all treated cows Treated cows should be identified using a dye or coloured tape. Details should be displayed in the milking area. Keep a record of all treated cows

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• • •

• • • • • • • • •

Records should identify the cow treated, the date of treatment, the product used and the withdrawal period. This is now the law. Withhold milk from treated cows for recommended time Read instructions carefully and note the withdrawal period. Obtain instructions from your veterinary surgeon, regarding the withholding period, if the milking cow is injected with a drug or antibiotic. Withhold and test milk from recently calved or purchased cows and heifers Be aware of cows calving early after dry cow therapy and cows which hold antibiotics in their system longer than usual. Milk treated cows last or rinse equipment with warm water Research has shown that cold water rinsing of milking jars may not remove all antibiotics from the glass as many antibiotics are oil based. Ensure no leakage into the milk transfer system through the recorder jar outlet valve Many milking parlours now have dump buckets / lines to isolate contaminated milk, preventing accidental transfer of milk. Inform buyer if contaminated milk enters bulk tank A sample of the milk should be tested before collection. On farm testing kits are now available for antibiotic testing. Quality Milk for Everyone

Where drugs are used on the dairy herd there is always a risk of antibiotic contamination of milk. Therefore the utmost care should be taken during the milking routine to minimise the risk of antibiotics entering the food chain. Milk of the highest quality is necessary to meet present and future market requirements and consumers now demand milk products of the highest quality and safety. DRUG SCREENING TESTS FOR ON-FARM USE Standard Testing For years, the standard for antibiotic testing has been the Bacillus stearothermophilus disc assay method. This was the official test for regulatory use. A few other tests which mimic the results of the disc assay were also approved. They were designed to detect residues of penicillin, the most commonly used antibiotic. Penicillin may still be the antibiotic of choice for treating selected diseases of lactating cows. However, other antibiotics are now being used. Many of these antibiotics are being used in an "extra label" fashion. That is, they are prescribed by veterinarians to be 7

used in a way not indicated by the manufacturer's labeling information. Often, this means that the withholding times necessary before the milk can be used for food are not well established. Antibiotic residues above the FDA-established "safe" or tolerance levels could be present. The disc assay is not adequate to detect antibiotics at this level nor does it effectively detect the range of antibiotics currently used. Random Testing To detect milk with antibiotic residues above the legal limit, regulatory agencies have relied on random and regularly scheduled sampling of producer and market milk. Many plants have tested for penicillin residues on a regular or intermittent basis. In addition to the official tests,( i.e., the disc assay) and some screening tests designed to reproduce the results of the disc assay, additional screening tests appeared on the market. Some of these screening tests had the ability to detect penicillin-like beta lactam antibiotic residues at lower levels than could be tested by the official tests. New tests appearing on the market also detected antibiotics other than the beta lactams, prompting widespread reports of antibiotic residues in milk. Modern technology can detect drug residues down to parts per billion. One (1) part per billion is equivalent to one (1) second in 32 years. Dilution will therefore almost never be sufficient to eliminate trace amounts of drug residues. Hence, the solution to milk contaminated with drug residues is NOT dilution. Dairy processors can protect the milk supply by testing milk for penicillin, sulfa drugs and other antibiotics before accepting each shipment at the dairy plant. In addition, efforts continue to educate producers and veterinarians on the need to eliminate drug residues from the milk supply.

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Processors have a key role in ensuring that milk containing drug residues is not accepted at dairy plants and processed into finished dairy products.

The Screening Program The effectiveness and fairness of the residue monitoring and surveillance program hinges on the proper choice of the antibiotic screening test to be used and its proper application by the analyst. In order that the industry might meet the requirements to screen every bulk milk pickup tanker prior to its being processed, FDA has established training and certification procedures for industry analysts. As of July 19, 1994, all bulk milk tanker drug screening tests must be performed by either an Industry Supervisor, or an Industry Analyst. In order to understand these procedures, the following terms are defined:

Industry Supervisors (IS) are designated industry representatives who are trained by state LEO's to perform specific official drug screening tests. They and their "backup supervisors" are to supervise their company's screening program and train IA's.

Industry Analysts (IA) are analysts designated and trained by Industry Supervisors to perform drug residue screening tests. The IA's certification is only valid for the time his Industry Supervisor's certification is valid.

State Laboratory Evaluation Officers (LEO) have attended FDA's test kit workshops are eligible to train Industry Supervisors. They have the responsibility to train and certify industry personnel and laboratories.

Certified Industry Supervisors (CIS) are analysts in an official NCIMS certified laboratory who are certified to perform various tests for regulatory action. Industry Supervisors, or their designated IA, may screen bulk milk pickup tankers. They may not open a regulatory sample to identify a positive producer. However, a certified analyst or a CIS may split the sample in an NCIMS Certified Laboratory. In order for regulatory action to be taken for 9

or against a producer, it must be based on the results from an NCIMS Certified Laboratory. Laboratories can be certified to do drug testing only.

Troubleshooting Antibiotic Residues in milk

Causes

Solutions

Milk from treated cow(s) enters bulk tank or cow(s) shipped for slaughter before end of withdrawal time: • •

No permanent written records of treatment(s) Poor identification of treated cows

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Forgetting cow was treated

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Poor communication between person who treats the animal and person who milks

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Not keeping out all milk from all quarters of treated cows

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Milk line used as a vacuum source to milk treated cows when using trap bucket to withhold milk

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Separate milker unit not used for treated cows

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Milker unit not cleaned

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Make a permanent record of all treatments

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Identify all treated cows -use coloured leg bands, livestock marker -for computerized milking systems, program animal ID and withdrawal time into computer - bigger herds can create a separate treatment group

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Post treatment information on a designated message or bulletin board to ensure people milking are aware of treated cows and appropriate withdrawal time

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Discard milk from all quarters of treated cows.

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Check with equipment supplier to see whether current pulsation system can be adapted to provide vacuum to trap bucket

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Milk treated cows last or with separate equipment to ensure no contaminated milk can enter the milk supply

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Thoroughly clean milker unit between treated and 10

properly between treated & untreated cows •

Treated dry cows not separated from the milking herd

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untreated cows Separate dry cows from the milking herd Identify dry cows with coloured leg bands or livestock marker Use appropriate antibiotic test

Prolonged drug withdrawal time because antibiotics used in extra-label fashion: •

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Antibiotic drugs used at a higher dosage and/or more frequently than label instructions

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Consult a veterinarian before using extra-label or off-label antibiotic treatment(s)

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Make a permanent record of all treatments including the animal ID, antibiotic given, dosage and number of treatments, method of administration, and withdrawal time

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Use only approved livestock medicines, and only according to label instructions or according to a veterinarian's prescription

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Use appropriate antibiotic tests

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Be diligent about obtaining treatment history of animal at time of purchase from previous owner.

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Use appropriate antibiotic tests

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Confirm date of dry-off treatment for freshened cows to determine whether adequate withdrawal time has been observed

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Consult your herd veterinarian • Use appropriate antibiotic test

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Medicated feeds for non-lactating dairy cows should be stored separate from the milking herd feeds

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Remove all traces of medicated feed from storage

Livestock medicines administered by a route different from label recommendations Using antibiotic drugs not approved for use in lactating dairy cattle

Purchasing cows that have been treated

Dry cows that have been dry-treated calve earlier than withdrawal time on label Feeding medicated feeds

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and feed handling equipment •

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Cows' udders treated with antibiotic ointments, salves and sprays

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Use only approved products

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Follow recommended with-holding times

Foot treatments where medicated solutions have been used to combat infectious diseases of the feet

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Use only according to a veterinarian's prescription

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If possible do not treat cows during milking to avoid possible contamination with milk or milking equipment

Summary and

conclusion for Safe Drug Use:

1. Read and follow label directions. 2. Administer drugs properly including teat end preparation. 3. Mark and identify all treated cows. 4. Keep a written record of all treatments and communicate this to all milkers. 5. Milk all treated cows last using special precautions such as separate milking units and remove fill pipe from bulk tank. 6. Discard milk from all 4 quarters of all treated cows. 7. Avoid "home-brews."

8. Test every cow with appropriate screening test. Where drugs are used on the dairy herd there is always a risk of antibiotic contamination of milk. Therefore the utmost care should be taken 12

during the milking routine to minimize the risk of antibiotics entering the food chain. Milk of the highest quality is necessary to meet present and future market requirements and consumers now demand milk products of the highest quality and safety. Where drugs are used on the dairy herd there is always a risk of antibiotic contamination of milk. Therefore the utmost care should be taken during the milking routine to minimize the risk of antibiotics entering the food chain.All these must be checked as it causes health concerns in humans

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REFERENCES:  www.ces.ncsu.edu/depts/foodsci/ext/pubs/antibioticresidues.html  Andrew, S.M.2007. Antibiotic residue tests for individual cows“an

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update. p. 191-201 in Proceedings 36th Annual Meeting, National Mastitis Council, Madison, WI. Bishop, J. R., S. E. Duncan, G. M. Jones, and W. D. Whitier2007. Evaluation of animal drug residue detection methods. p.141-152 in Proceedings 31st Annual Meeting, National Mastitis Council, Madison, WI. Boeckman, S. and K.R. Carlson. 1998. Milk and Dairy Beef Residue Prevention Protocol 1999 Producer Manual. Agri-Education, Inc., Stratford, IA. Cullor, J.S., A. VanEenennaam, I. Gardner, W. Smith, L. Perani, J. Dellinger, L. Jensen, and W. Guterbock. 2006. Problems associated with cowside and bulk tank antibiotic residue testing. p. 133-143 in Proceedings 32nd Annual Meeting, National Mastitis Council, Madison, WI. Seymour, E.H. 2008 Persistence of residues in milk

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