“Antibiotic (Tylosin) in Honey”

Bee Culture (December 2005), Vol. 133 (12): 20-22

 

By

 

Dr. Malcolm T. Sanford
http://apis.shorturl.com

 

The comments by Editor Kim Flottum in the October, 2005 Bee Culture with reference to testing honey are timely.  Perhaps it’s indeed the hour to “talk about something nobody wants to talk about.”  I have received unconfirmed reports that antibiotic is being found in U.S. honey like other places in the world confronted with Terramycin®-resistant American foulbrood.  Fortunately, examples of this appear to be few at the present time. 

 

The antibiotic involved is tylosin lactate, sometimes simply called tylosin.  It has different properties than the product Terramycin®, often referred to as TM, which is formulated using oxytetracyline (Oxy-Tet).  There is zero tolerance for tylosin in honey, meaning that any amount found, no matter how small, will likely result in marketing and regulatory consequences.  Although veterinarians might prescribe tylosin as an “extra label drug use” (see discussion below), this is void if a “violative food residue, or any residue which may present a risk to public health” is found.

 

I am shocked but not surprised at this turn of events.  It was retiring Dr. Bill Wilson in this magazine who stated, “The U.S. Beekeeping industry could be faced with a widespread epidemic of American foulbrood disease (AFB) that would be just as destructive as uncontrolled infestation of varroa mites.  This scenario could take place if beekeepers fail to control Terramycin-resistant AFB and scientists fail to develop an effective substitute…”1

 

Is history repeating itself?  I reported in my Apis newsletter over a decade ago that: “While at the Fifth Ibero Latin American Congress on Apiculture held May 30 through June 2, 1996 in Mercedes, Uruguay, I learned what can happen when AFB gets out of hand. Since it was first discovered in Argentina in 1989, the beekeepers in that country have gone through three stages in controlling AFB, according to Marcelo del Hoyo of the veterinary faculty, University of Buenos Aires. The first was denial, when the name American foulbrood was not uttered. When the disease was finally recognized in affected areas, beekeepers tried to combat the problem locally, but it was still ignored elsewhere in the country. The present stage is a mature condition where most good apiculturists have been exposed to the disease and have at least temporarily treated the problem.

“The fact that Argentinean beekeepers went through the above phases, however, appears to have led to something more serious than in other parts of the world.  It is the only country to my knowledge where Paenibacillus larvae has become resistant to oxytetracycline.  This was confirmed in a study reported at the Mercedes congress by A. Alippi and M. Aguilar (National University of Mar de la Plata). They used biochemical techniques (PCR) to analyze bacterial DNA. Resistance was found in only 28 percent of samples, but this translated to 58 percent of tested locations in the country.

“Argentine researchers reported on another product, tylosin lactate (evidence of its effectiveness was first published by John Hitchcock and colleagues at the Laramie Bee Laboratory in the Journal of Economic Entomology. 63:1, pp. 204-207, February, 1970), which they say will control the disease as an alternative to Erythromycin and oxytetracycline.”2

Dr. Nick Calderone at Cornell University writes the following that concurs with Dr. Wilson’s assessment and might parallel the Argentine situation:  “With the emergence of TM resistant AFB, beekeepers have no way to protect themselves from AFB. The USDA-ARS Bee Research Laboratory in Beltsville, MD has done a great deal of work evaluating a number of other antibiotics for use in AFB management. The most promising is an antibiotic called TYLAN (a formulation of tylosin). It is very effective; however, the FDA is probably going to approve it for use as a treatment for active AFB, NOT as a preventative for use on healthy colonies. The results could be disastrous. Why? TYLAN, like TM, is only effective against the vegetative stage of AFB. The spores survive to germinate at a later date. If you suppress the disease, then transfer combs among colonies, all of your colonies will eventually have AFB. Then, you will need to keep all of your colonies medicated.”3

He futher quotes Dr. Mark Feldlaufer, Research Leader at the USDA Beltsville Bee Laboratory: “While a large amount of work has been completed, we are not done. FDA must review all material submitted, and everything dealing with antibiotic use in agriculture is being scrutinized. The January 6, 2001 issue of the N.Y. Times pointed to the (over) use of antibiotics in farm animals merely for the prevention of disease. A Jan. 19th editorial in the prestigious journal SCIENCE stated that ‘Using the same antibiotics in people and animals is a bad idea.’ and a Feb. 19th article in Chemical & Engineering News was titled ‘Furor over animal antibiotic use’. Faced with this intense scrutiny, FDA has indicated the shortest route to approval is as a ‘dust’ and for the ‘control’ of AFB. Syrup with antibiotic poses a greater residue risk, while ‘preventative’ treatments for AFB amount to using an antibiotic in the absence of disease, a policy being reviewed by FDA. Even with ‘dusting’ for the ‘control’ of AFB, I’m guessing approval for lincomycin and/or tylosin is at least a year away.

“So, what can a beekeeper do when faced with Terramycin-resistant AFB in the interim? There is something known as ‘AMDUCA’. This stands for the ‘Animal Medicinal Drug Use Clarification Act of 1994’, and it allows for the extra label drug use (ELDU) of certain approved antibiotics. ‘Extra label use’ means using an antibiotic approved for let’s say chickens and swine, for honey bees. The key is that the antibiotic needs to be prescribed by a veterinarian!” 

I looked up the following information about the Animal Medicinal Drug Use Clarification Act: 4

Requirements For Extra Label Drug Use (ELDU)

  • ELDU is permitted only by or under the supervision of a veterinarian.
  • ELDU is allowed only for FDA approved animal and human drugs.
  • A valid Veterinarian/Client/Patient Relationship is a prerequisite for all ELDU.
  • ELDU for therapeutic purposes only (animal's health is suffering or threatened). Not drugs for production use.
  • Rules apply to dosage form drugs and drugs administered in water. ELDU in feed is prohibited.
  • ELDU is not permitted if it results in a violative food residue, or any residue which may present a risk to public health.
  • FDA prohibition of a specific ELDU precludes such use

Label Requirements Include:

  • Name and address of the prescribing veterinarian.
  • Established name of the drug.
  • Any specified directions for use including the class/species or identification of the animal or herd, flock, pen, lot, or other group; the dosage frequency, and route of administration; and the duration of therapy.
  • Any cautionary statements.
  • Your specified withdrawal, withholding, or discard time for meat, milk, eggs, or any other food.

Alberta’s provincial apiculturist Dr. Medhat Nasr writes that the Canadians have also used this approach:  “Recent finding of levels of prohibited antibiotics in honey imported from China and Argentina has resulted in recalling honey from the market around the world.  The public has become aware of this issue. It also has increased the surveillance program for residues analysis in honey around the world.  In addition, the chances of finding residues of antibiotics in honey has increased due to: 1) improved technology for residues analysis in honey, 2) extracting honey combs from the brood boxes, 3) increased residues in bee colonies from the repeated administration of antibiotics in bee colonies, and 4) extra-label use of antibiotics such as Tylosin that does not have Maximum Residues Limit (MRL) required more inspection to ensure no residues in any produced honey.

“For interim solution, Alberta beekeepers could use the veterinarian- Extra-label use privilege for getting Tylosin. For long-term solution, Alberta Agriculture, Food and Rural Development (AAFRD) is conducting aggressive educational programs for advocating and promoting integrated pest management practices for AFB control. Alberta Beekeepers Association in a partnership with AAFRD is also supporting a research program at Agriculture and Agri-Food Canada, Beaverlodge, Alberta. The objectives of the research program are: 1) to develop information for registration of alternative antibiotics for treatment of oxy-tet resistant AFB, 2) develop methods for prediction of AFB infection in bee colonies, and 3) to improve resistance of honey bees to AFB. The Agriculture and Agri-Food Canada, Canadian Honey Council and the ABA also are working towards getting Tylosin registered for use in bee colonies.

“Alberta is a honey-exporting province. Finding any residues in honey could affect the market access. Therefore, AAFRD has taken the lead in working with the Alberta Beekeepers Association (ABA) and has initiated the honey surveillance program. This program is a surveillance and extension project, not a regulatory program.  The objectives of the project include determining management practices that result in detectable antibiotic residues in honey, developing best management practices to eliminate residues, and following up with individual beekeepers who have detectable residues in their honey. Thus, Alberta Agriculture will be able to help Alberta beekeepers in ensuring production of high quality honey that meets the consumers' expectations. It also will address the market access issues and promote the safety of Alberta honey.”5

As Editor Flottum points out, most U.S. producers are not exporters and so not faced with as stringent controls as those in exporting countries like Canada. This means he concludes: “No one knows what’s happening in the U.S.  Or no one is saying.”

Word of mouth and various writings appear to have communicated the message that tylosin works as West Virginia WVDA State Apiarist George Clutter is reported to have said, “even better than the Terramycin did.”6  A significant problem seems to be that many are using the material like they did Terramycin as a preventative (prophylactic), may also be mixing it in similar proportions (tylosin is much more concentrated) and/or feeding it in syrup, which further increases the risk of honey contamination.

 

Here’s what Harry Fulton, Mississippi’s State Apiarist writes, “Terramycin has been used by beekeepers since the early 1950s for the control of AFB, and the development of terramycin-resistant AFB has long been a serious concern. Without an effective antibiotic to combat AFB, the only way to deal with AFB is to destroy by burning hives and bees with the disease. Work carried out by the USDA Bee research labs in conjunction with beekeepers and state apiary personnel around the country has shown that the antibiotic, tylosin, is effective at controlling AFB and has substantial safety for both bees and human. Elanco, the producer of tylosin, will be submitting the paperwork for registration of Tylan for use in honey beehives. Mann Lake Ltd. will be selling the product in bulk and in tea bag-like individual packets. Mann Lake will not be the sole source of the product. The antibiotic will be registered only for therapeutic use (after you see the disease signs) and for use only in “dust” formulations. Jan Kochansky of the USDA Beltsville Bee Lab recently reported (Journal of Apicultural Research, vol. 43, pg. 65, 2004) on his studies of tylosin residues in sugar syrups and honey. It can take 1 to 3 years for tylosin and its first breakdown product (also effective in controlling AFB) to breakdown further in honey. Tylosin was shown to have a half-life of about 75 days in sugar syrup. Thus, if you feed it to your bees in syrup you will very likely exceed the tolerance level in your honey crop. Without question, tylosin presence and levels will be monitored by regulatory personnel.”

 

Editor Flottum points out that questions remain concerning how much contamination is too much and that testing for residues in honey is not an exact science.  These are academic, however, because again there is no residue limit for tylosin in honey in the U.S.  That means “zero tolerance,” and in the brave new world of continually improving testing technology this can only mean that if one uses tylosin, it will be detected.   Terramycin® was much more forgiving because it did break down readily in liquid (so much so that it was more effective as a dust) and honey. 

 

Breaking news as I complete this column is that a label for TYLAN® (tylosin tartrate) has been approved by the U.S. Food and Drug Administration.8   The details so far have  yet to be made available.  Whether labeled or not, one conclusion is increasingly clear.  Using tylosin for AFB control, especially as a prophylactic and in liquid form, could be a “smoking gun” in the making when it comes to honey contamination.  Due diligence is demanded of all when using this material.

 

References:

 

1.  Wilson, W.T. 2000.  “An overview of Foulbrood in the United States; the past 45 years,” Bee Culture Vol. 128, No. 10, pp. 24-28

<http://maarec.cas.psu.edu/PDFs/Dec2000-87.pdf>, accessed October 19, 2005.

 

2. Sanford, M.T. 1996. Apis Newsletter, University of Florida, August <http://apis.ifas.ufl.edu/apis96/apaug96.htm#1>, accessed October 19, 2005.

3. Calderone, N.  2004. Northeast Master Beekeeper Newsletter, Vol. 1, No. 1. January
<http://www.masterbeekeeper.org/northeast2.htm >, accessed October 19, 2005.

4.  Animal Medicinal Drug Use Clarification Act <http://www.avma.org/scienact/amduca/amduca1.asp>, accessed October 19, 2005.

5.  Nasr, M. 2004. Antibiotic Residues: An Issue for Honey Producers, Alberta Beekeepers Newsletter, August <http://www.albertabeekeepers.org/Articles/2004%20Antibiotic%20Residues.html>, accessed October 19, 2005.


6.  West Virginia Department of Agriculture Press release 4/11/02 <http://www.wvagriculture.org/news_releases/2002/4-11-2002.htm>.

 7. Fulton, H.  2005.  New Antibiotics for Control of AFB on the Horizon (from The Antenna January 2005).  Mississippi Beekeeper’s  Association  Bee News & Views <http://www.msstate.edu/Entomology/beenews/beenews0605.htm>, accessed October 19, 2005.

8.  FDA Center for Veterinary Medicine <http://www.fda.gov/cvm/CVM_Updates/honeybee.htm>, accessed October 21, 2005.

 

 



 


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