DVM, MS, DACPV
Manager, Poultry Technical Services
Phibro Animal Health
Watkinsville, Georgia, USA
Introduction
It seems like almost every week we read or hear a news report about the dangers of using antibiotics in food-producing animals. The stated concern is that antibiotic use in food-producing animals could create antibiotic resistance in the bacteria present in those animals and that those bacteria could end up in the people that eat their meat. Subsequently, when the people need treatment with an antibiotic, the treatment may fail because the bacteria were resistant.
Theory vs. Reality
Although the theory outlined above seems reasonable at first glance, when one starts examining the facts closer a different picture emerges.
Of the most serious 20 bacterial infections exhibiting problems with antibiotic resistance in human medicine, 12 are in no possible way related to antibiotic use in foodproducing animals, as these bacteria cannot be acquired via the food chain. Of the remaining 8, assuming that transfer of bacterial resistance from animals to people occurs (an unproven assumption in most cases), the calculated percent contribution to antibiotic resistance in all cases is 1% or less, in most cases less than 0.5% (4). Likewise, results from the SENTRY Antimicrobial Surveillance Program, which since 1997 has analyzed worldwide data on antibiotic resistance patterns from both, human and animal bacterial isolates has found little significant association between human and animal patterns (13). According to Ron Jones, MD, results from the SENTRY Antimicrobial Surveillance Program “clearly show a disconnect between antibiotic resistance patterns in humans and animals, calling into question the alleged link between resistant bacteria in animals and those in humans”.
Science vs. Politics
The European Union (EU) first banned the use of avoparcin (a widely used antibiotic feed additive) against the advice of its own Scientific Committee for Animal Nutrition (SCAN). Invoking the precautionary principle, the EU banned the use of avoparcin in animal feeds in 1997. The rationale behind the ban was that avoparcin use in foodproducing animals had created a large reservoir of resistance in the animal and human populations for vancomycin, another antibiotic in the same class, used in human medicine to treat potentially life-threatening nosocomial infections caused by Enterococcus faecalis and Enterococcus faecium. Avoparcin was banned despite the opinion of EU experts who found no scientific evidence to support the ban. It is interesting to note that despite the fact that avoparcin has never been used as an antibiotic feed additive in foodproducing animals in the United States, Vancomycin-Resistant Enterococcal (VRE) infections are far more common and problematic in the US than in the EU.
The 1999 EU ban on virginiamycin reveals a very similar story. A detailed review of scientific evidence by the SCAN concluded that there was no new scientific evidence of virginiamycin transfer from animals to humans. In addition, the SCAN pointed out that in the US and France where virginiamycin has been used in food-producing animals for over 30 years, the efficacy of antibiotics used in human medicine belonging to the same class had not been compromised. In fact, the results of a very extensive US and Canadian survey on streptogramin resistance in E. faecium (12) showed that after 30 years of continuous virginiamycin use in food animals, only 0.2% of over 1000 human clinical isolates tested were resistant to Quinopristin/Dalfopristin (Q/D), the newest streptogramin antibiotic introduced in human medicine to treat VRE infections.
In addition to virginiamycin, the EU also banned in 1999 the use of 3 other antibiotic feed additives used in food animals; bacitracin, spiramycin and tylosin. The remaining antibiotic feed additives are scheduled for withdrawal during this year, including several ionophore antibiotics.
All of the above has occurred in spite of detailed scientific reviews showing the lack of conclusive scientific evidence of antibiotic resistance transfer from animals to humans. One of these reviews was conducted by the Heidelberg Appeal Nederland (3) that groups almost 200 academics and concluded that “documented in-vivo cases showing spread of antimicrobial resistant Gram-positive bacteria from livestock to humans are in essence non-existent”.
Likewise a comprehensive literature review by the National Research Council in the United States (14) concluded that “the use of drugs in the food animal production industry is not without some problems and concerns, but it does not appear to constitute and immediate public health concern”. Another review by the US General Accounting Office (11) stated in some of its conclusions that “Debate exists over whether the role of agricultural use in the overall burden of antibiotic-resistant infections of humans warrants further regulation or restriction”, and that “In developing a federal response, both human health concerns and the impact on the agriculture industry are factors to consider”.
Responsible antibiotic use
Although the enemies of modern animal agriculture always try to portray the practices conducted in intensive production of food-producing animals as unnecessary or “irresponsible”, the truth of the matter is that at least in the United States, all integrated producers try their best to follow best production practices, and the use of antibiotics in particular, by enlarge is handled in a very responsible way. For example, in the poultry industry, antibiotics like enrofloxacin (Baytril®) are only used by order of a licensed poultry veterinarian when bacterial cultures and antibiotic sensitivities have been conducted on samples from sick birds indicating that enrofloxacin is the only antibiotic that shows significant efficacy against the infectious agent. The poultry veterinarian must ensure compliance with specific drug withdrawal periods, meet all the requirements of a valid doctor-patient relationship and in addition, maintain a logbook recording specific details about the use of this drug. This logbook is available for inspection by Food and Drug Administration (FDA) inspectors if needed. As a result of these requirements and other concerns like the cost of the drug, enrofloxacin is used in a very responsible way and in a very small percentage of the total number of birds produced for human consumption.
Likewise, the antibiotic feed additives currently approved for use in food-producing animals are used by the poultry industry in strict compliance with Federal and State laws. Their use at feed mills is strictly regulated and monitored by FDA inspectors who have access to all production records from any feed mill. These additives can only be used at the concentrations approved by the FDA and as listed in the Code of Federal Regulations (CFR), likewise, they can only be used in combination with other feed additives as specifically approved by the FDA and as listed in the CFR. In addition, feed mills must be re-certified each year by submitting a minimum number of drug assays to ensure that the drugs used are present in the feed at concentrations within the specified “PAV” (permitted analytical variance) for each drug. It is also important to note that the old term “growth promoter” was coined nearly fifty years ago when antibiotics were first tested in animal feeds and antibiotic resistance was not a subject of fascination with activist groups opposed to modern animal agriculture practices. A more important question, would have been why or how do feed additive antibiotics improve animal performance? As we now know and as reported by others (5, 29), antibiotic feed additives used at levels considered for “growth promotion” actually have significant prophylactic and health promotional effects previously unrecognized. Research data documenting the disease prevention benefits of antibiotics like virginiamycin (Stafac®) even when used at levels considered for “growth promotion” are already published and available to any interested people (25, 28).
Additional safeguards for the consumer include the routine monitoring of drug residues in edible tissues from food-producing animals by USDA/FSIS. In addition, the USDA has developed a Food Animal Residue Avoidance Databank known as FARAD (http://farad.org) that provides valuable information to producers, extension specialists and veterinarians on how to avoid drug, pesticide and environmental contaminant residue problems.
Finally, the American Veterinary Medical Association (AVMA) in cooperation with the FDA Center for Veterinary Medicine (CVM) and various associations of specialized veterinarians have developed specific guidelines for antibiotic use in food-producing animals (21-24).
Why antibiotic prescription practices by physicians in private practices and private and public hospitals have not received the same degree of scrutiny and remain unmonitored and unchallenged is a question that remains unanswered.
Consequences of bans on animal health and antibiotic use
The most obvious and immediate consequences of the EU bans on antibiotic feed additives for food-producing animals were reflected in animal health and therapeutic antibiotic use. The bans have led to an increased incidence of enteric diseases in foodproducing animals, in addition to productivity and mortality losses; the bans have resulted in an increased use of antibiotics for therapeutic purposes.
In Sweden, Wierup (20) reported increased incidence of necrotic enteritis in broiler chickens requiring antibiotic treatment. Likewise, Inborr (4) reported increased incidence of diarrhea in piglets. In Denmark, although overall antibiotic use is lower than it was before the bans, therapeutic antibiotic use has increased (10). In addition, a 10% increase in diagnosis of ileitis in young pigs has been reported (DS Laboratory – Kjellerup).
As in other EU countries, the French broiler industry experienced a 51% increase in use of antibiotics for treatment of necrotic enteritis after the bans. In Holland, consistent increases in tons of antibiotics used for disease treatment were seen, despite the fact that animal numbers had decreased (National Statistics of Animal Health Products, 2001). Germany saw a 13% increase in use of therapeutic antibiotics in food animals following the bans (I & G Report, 2001).
In the United Kingdom, according to the records kept by the Veterinary Medicines Directorate following the 1999 bans, there was nearly a 10% increase in use of therapeutic antibiotics from 1999 to 2000 with food animals accounting for 94% of sales (http://www.vmd.gov.uk/sarss.htm). An increase of 54 tons of antibiotics for therapeutic usage overshadowed a 4-ton decrease in antibiotic usage for growth promotion.
All of the above is in agreement with the findings reported in a recent scientific manuscript by M. Casewell et. al. (5) showing that the bans on feed additive antibiotics for food-producing animals have had adverse repercussions on animal health. According to the authors, there has been an increase in morbidity and mortality in swine, primarily associated with enteric infections, as well as an increased incidence of necrotic enteritis outbreaks in poultry. The increased incidence of enteric infections has resulted in a significant increase in the volume of antibiotics used for therapeutic purposes. For example, Denmark has seen a 95.8% increase in antibiotic usage for treatment of enteric diseases. Unfortunately, the increased has come primarily from those classes of antibiotics more frequently used in human medicine (tetracyclines, macrolides, lincosamides and aminoglycosides).
Therefore, instead of reducing the risk of antibiotic resistance for humans, the bans appear to have had the opposite effect as reported by the same authors in regards to the increased incidence of antibiotic resistance in Salmonella and Campylobacter.
Consequences of bans on human health
Antibiotic feed additives play a positive role on food safety and human health by keeping flocks healthy and preventing outbreaks of enteric diseases like necrotic enteritis. By preventing necrotic enteritis, the therapeutic use of other antibiotics more commonly used in human medicine is avoided.
In addition, and as reported by others (30), by preventing diarrheic diseases and improving bird uniformity, antibiotic feed additives result in less incidence of ruptured gastrointestinal tracts at the processing plant, intestinal spillage and potential contamination of raw carcasses with pathogens like Salmonella, E. coli and Campylobacter. There is also evidence confirming that the incidence of bacterial contamination with potential pathogens like E. coli and Campylobacter is higher in airsacculitis positive flocks vs. airsacculitis negative flocks (31).
Antibiotics effective against airsacculitis, administered at therapeutic levels in the feed or the drinking water or both, should result in a reduction in the total amount of bacterial contamination found on the carcasses during the processing of flocks at the slaughter plant.
Supposedly all the bans on antibiotic feed additives for food-producing animals were implemented for the sole purpose of reducing antibiotic resistance problems in human medicine.
Therefore, several years after the bans were implemented, it is reasonable to ask: Has the objective been achieved? Not according to a recent scientific manuscript by Casewell, et al. (5) who reported that there has been “no diminution in the prevalence of resistant enterococcal infection in humans”, instead, according to the authors “vancomycin resistance appears to be increasing in enterococcal infections in parts of Europe over the period of the ban”.
What about the incidence of, and antibiotic susceptibility of the major foodborne illnesses, salmonellosis and campylobacteriosis? According to the same authors, “human salmonellosis has not responded to control measures in some parts of Europe, and microbiologically confirmed infections actually increased in prevalence in Denmark in 2001 after they had declined for 3 years”. The same authors state that regarding campylobacter the situation may be even worse “in Denmark, it has steadily increased in prevalence over the past decade and there is more tetracycline and fluoroquinolone resistance in human than in animal isolates”.
The European Union’s double standard
A double standard exists in regard to antibiotic use in food-producing animals in the EU, as poultry, swine and cattle are in most cases not raised “antibiotic-free” but rather raised without antibiotic growth promoters. As shown earlier, the lack of antibiotic feed additive use has resulted in higher incidence of enteric disease outbreaks in foodproducing animals, this in turn has resulted in the use of higher levels of antibiotics, and the use of antibiotics of much more importance in human medicine than the ones used in the feed before the bans. As pointed out by Casewell et. al. (5), “The published evidence suggests that the growth-promoter bans have reduced overall antibiotic use in foodproducing animals. It is increasingly clear, however, that the use of growth promoters was accompanied by other, previously unrecognized, health promotional or prophylactic effects”.
The focus on food-producing animals
From the results previously discussed, it is clear that even if one assumes that antibiotic resistance transfer from animals to people occurs (an unproven assumption in most cases), the potential contribution of food-producing animals to the overall antibiotic resistance problem would be minimal to nil.
On the other hand, a 2-year long survey on antibiotic resistance in a community, conducted by researchers from Wales and published in the British Medical Journal (16) clearly documents the positive correlation between antibiotic prescribing practices in a community and the development of antibiotic resistance in the same community. The number of prescriptions written on a yearly basis per 1000 patients produced practically a mirror image when compared to the average resistance rate in bacteria isolated from surgical samples from the community hospital. In all cases, the higher the number of prescriptions written for a given antibiotic, the higher the average resistance rate in the bacteria tested from the surgical samples.
Therefore, it is distressing to see that for the most part the antibiotic resistance debate has been restricted to antibiotic use in food-producing animals. Clearly, and even with the acknowledgement of the World Health Organization (WHO), antibiotic prescription by medical doctors in human practice is the driving force behind the antibiotic resistance problem. Also clearly, of the 2 distinct animal populations, food-producing animals and companion animals, and as pointed out by others (1,2,6,15), companion animals are a much more likely source of antibiotic resistance transfer to humans than food-producing animals.
First of all, recent polls among the American people have shown that a large percentage of the population consider their pets as members of the family, and a significant percentage has admitted to letting their pets sleep in bed with them or in their bedrooms. Many pets live in intimate contact with their owners. In many cases, there is frequent tongue to face and mouth-to-mouth contact. In addition, indoor litter boxes for pets are a common sight in many households. Many pets live indoors and from time to time pets defecate and urinate indoors. Ask yourself, where is the chance for a significant germ exchange greater, between a baby or a child and his/her puppy or kitten? Or between that baby or child and a raw piece of chicken? I have witnessed many times dogs licking their owners’ faces and lips, including babies and children, but I am yet to witness a baby or a child lick a piece of raw chicken. All of us should remember that before chicken is consumed, it is cooked, and during this process the bacteria that might have been on it are destroyed.
Dogs, cats and other companion animals get treated with the same classes of antibiotics often prescribed in human medicine with little to no supervision by any regulatory agency, in much the same way as those prescribed by medical doctors to their patients. So it is difficult to comprehend why scientists and politicians are most concerned with antibiotic use in food-producing animals, instead of antibiotic prescription practices by medical doctors and companion animal veterinarians.
According to many experts, it makes little sense to ban antibiotic use in food animals over concerns of increasing antibiotic resistance in human medicine.
Following are just a few quotes taken from the experts:
- “We have so many problems in hospitals that it is hard to imagine that veterinary uses are significantly contributing to microbial resistance in humans” (19).
- “If all animal uses of antibiotics were terminated today, there is no evidence that human health would measurably benefit, while animal health would certainly suffer, and possibly human health as a consequence” (17).
- “We suggest that the role of food-producing animals in the origin and transmission of antimicrobial resistance and foodborne pathogens has been overestimated and overemphasized in the scientific literature; consequently, nonfoodborne transmission, including pet-associated human cases, has been underemphasized” (2).
- “While the initial value of sub-therapeutic antibiotics in animals was discovered as an improvement in growth and efficiency, and therefore were termed growth promoters, antibiotics are health promoters that lead to improved growth and efficiency of animal protein production” (18).
So one has to wonder if there are other factors, such as the fear of taking on the American Medical Association or the American Veterinary Medical Association, or on the known emotional bond between people and their pets, that are causing the debate be primarily centered around antibiotic use in food-producing animals.
Politically motivated bans vs. Scientific risk assessments
It seems like the activist groups determined to make animal agriculture an unprofitable business, and frustrated by their lack of success on the scientific front with the US Food & Drug Administration Center for Veterinary Medicine (FDA/CVM), have now turn their efforts to lobbying Washington politicians to impose their views on the rest of us by legislative mandate.
Recently under review in the House of Representatives in Washington, DC, was a bill (H.R. 2932) sponsored by Rep. Sherwood Brown (D-OH) entitled “The Preservation of Antibiotics for Medical Treatment Act” that proposes to eliminate use of 8 antibiotic feed additives considered “growth promoters” with equivalent counterparts in human medicine. The same bill is being sponsored in the senate by Sen. Ted Kennedy (D-MA). It is a clear attempt by activist groups opposed to animal agriculture, to bypass the regulatory system that has established the FDA/CVM as the federal agency responsible for dealing with veterinary drug approvals and withdrawals, and the United States Department of Agriculture Food Safety & Inspection Service (USDA-FSIS) as the federal agency responsible for ensuring the safety of the food supply in the US.
FDA/CVM has emphasized the need for scientific risk assessments prior to determining the fate of any animal drug already approved for use in food-producing animals. Comprehensive risk assessments have been completed for 2 of the antibiotics used in food-producing animals of most concern to the scientists at the FDA/CVM and the Centers for Disease Control & Prevention (CDC).
We believe that although misled politicians may be willing to sponsor legislation like HR 2932 for political gain, the transparency of the scientific process must remain unchanged and in the hands of the capable scientists at the FDA/CVM.
The first scientific risk assessment, for the fluoroquinolone antibiotic enrofloxacin (Baytril®) showed that the human health risk from using this antibiotic in food-producing animals is practically nil. The second one, for the streptogramin antibiotic virginiamycin (Stafac®) was also completed and reported (7,8,9). Even when worst-case scenario conditions were used, like assuming that resistance transfer from animals to people occurs (an unproven assumption in this case), the risk assessment proved scientifically and conclusively that the human health risk from virginiamycin use in food-producing animals was negligible.
Perhaps, the activist groups and the politicians willing to sponsor their views on antibiotic use in food-producing animals should learn from the European experience, that it is clearly beginning to show the adverse consequences of the antibiotic feed additive bans on both, animal health and human health.
References
- Barber, D.A., 2001. New perspectives on transmission of foodborne pathogens and antimicrobial resistance. JAVMA, 218 (10): 1559-1561.
- Barber, D.A., G.Y. Miller and P.E. McNamara, 2003. Models of Antimicrobial Resistance and Foodborne Illness: Examining Assumptions and Practical Applications. Journal of Food Protection, 66 (4): 700-709.
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- Cervantes, H., 2002. The Antibiotic Resistance Debate: An Industry Perspective on the Use of Virginiamycin in Poultry and Livestock. Proc. United States Animal Health Association Salmonella Committee Meeting, October 20, Downtown Sheraton Hotel, St. Louis, Missouri, USA.
- Cox, Jr., L.A. and D.A. Popken, 2002. Human Health Risk Assessment for Virginiamycin Use in Chickens. Conference on Antimicrobial Resistance, Science-Prevention Control, National Foundation for Infectious Diseases, June 27-29, Hyatt Regency Hotel, Bethesda, Maryland, USA, p. 43.
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- Danish Integrated Antimicrobial Resistance Monitoring and Research Programme, 2001. Use of Antimicrobial Agents and Occurrence of Anitmicrobial Resistance in Bacteria from Food Animals, Food and Humans in Denmark. Danish Veterinary Laboratory, Copenhagen, Denmark.
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- American Veterinary Medical Association. Judicious use of antimicrobials for dairy cattle veterinarians.
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